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Review of aromatherapy essential oils and their mechanism of action against migraines
Abstract
Ethnopharmacological relevance
Migraines have become a major threat to human health, as they significantly affect human health and quality of life due to a high prevalence rate, attack rate and pain intensity. Aromatherapy, with its comfortable and pleasant natural characteristics and rapid and efficient characteristics, is widely favored by patients in the folk. Chinese folk also have the application history and related records of aromatic plants in the treatment of migraine.
Aim of the study
This study was conducted to review the pathogenesis of migraine, the application of plant essential oils in the treatment of migraine, and further explore the material basis and mechanism of action of plant essential oils against migraine.
Materials and methods
Search the electronic literature of essential oils with anti-migraine effect in Google Scholar, PubMed and China National Knowledge Infrastructure, and further search the research situation of the monomer components of essential oils in migraine, inflammation, pain and other aspects.
Results
studies show that there are 10 types of plant essential oils that could relieve migraine symptoms, and that 16 monomers may play a role in migraine treatment by effectively inhibiting neurogenic inflammation, hyperalgesia and balancing vasorelaxation.
Conclusion
Aromatic plant essential oils can relieve migraine effectively, these findings can be used as an important part of the development of anti-migraine drugs.
... Its use is popular in dialysis sessions to reduce neuropathic pain in kidney patients [23]. It is also very useful to relieve vascular complications induced by diabetes mellitus [32], treat symptoms in neurovascular dysfunction diseases [20], to provide relief from psychosomatic discomfort during the puerperium [24], to reduce symptoms in cardiovascular diseases [33], to treat neurodegenerative manifestations and age-related progressive deterioration [34], to treat discomfort in oncology patients [35], to relieve menopausal symptoms [36], to relieve restless leg syndrome [19], and for the treatment of both respiratory infections [37] and skin infections [25]. ...
... Aromatherapy is an alternative strategy used by patients for alleviation of their symptoms because acts against main migraine symptoms (pain, photophobia, nausea, and vomiting). Plants such as Chinese aconite (Aconitum carmichaeli, Ranunculaceae), Canada mint (Mentha canadensis, Lamiaceae), black Pepper (Piper nigrum, Piperaceae), Safflower (Carthamus tinctorius, Asteraceae), frankincense (Boswellia sacra, Burseraceae), myrrh gum (Commiphora myrrha, Burseraceae), sambong (Blumea balsamifera, Asteraceae), clove, melon (Cucumis melo, Cucurbitaceae), and ginger are some species recognized as antimigraine herbs [20]. ...
... It is shown that the plant families Apiaceae, Lamiaceae, and Rutaceae gather the largest number of promising species, while lavender, bergamot, geranium, rosemary, and peppermint are the species that have shown a wide spectrum of bioactivities. Zingiberaceae Curcuma longa L. Turmeric ↓ Mood alterations, ↓ stress, ↓ depression, ↓ anxiety, ↓ migraine, ↓ chronic pain, ↓ behavioral disturbances in dementia [11] Zingiber officinale Roscoe Ginger ↓ Nausea and vomiting, ↓ migraine, ↓ appetite disorders, ↓ flatulent, ↓ hemorrhoid, ↓ post-partum pain [20,[106][107][108] ↓ Decrease, ↑ Increase. ...
Complementary and alternative medicine (CAM) encompasses a variety of ancient therapies with origins in cultures such as those of China, Egypt, Greece, Iran, India, and Rome. The National Institutes of Health (NIH) classifies these integrative therapies into five categories: (1) mind–body therapies, (2) biological practices, (3) manipulative and body practices, (4) energy medicine, and (5) whole medical systems, including traditional Chinese medicine and Ayurvedic medicine. This review explores the role of biological practices utilizing aromatic plants, particularly through inhalation aromatherapy and massage with essential oils, as effective complementary strategies within health systems. The review compiles information on the most commonly used plants and essential oils for holistic health maintenance from a complementary and alternative perspective. Given their accessibility and relative safety compared to conventional treatments, these therapies have gained popularity worldwide. Furthermore, the integration of essential oils has been shown to alleviate various psychological and physiological symptoms, including anxiety, depression, fatigue, sleep disorders, neuropathic pain, nausea, and menopausal symptoms. Among the studied plants, lavender has emerged as being particularly notable due to its broad spectrum of therapeutic effects and its designation by the US Food and Drug Administration (FDA) as “Generally Recognized as Safe”. Other essential oils under investigation include eucalyptus, damask rose, sandalwood, vetiver, calamus, frankincense, chamomile, lemon, grapefruit, tangerine, orange, sage, rosemary, garlic, and black pepper. This study emphasizes the potential benefits of these aromatic plants in enhancing patient well-being. Additionally, it underscores the importance of conducting further research to ensure the safety and efficacy of these therapies.
... Aromatherapy, the use of high-quality plant-based essential oils through inhalation or topical application, is increasingly recognized as a complementary approach for managing migraines [153,154]. This practice offers an alternative to conventional pharmacological treatments, which are often accompanied by side effects and contraindications [155]. Essential oils contain bioactive compounds such as terpenoids, esters, and aldehydes, which contribute to their therapeutic effects [156]. ...
... Specifically, research has demonstrated that essential oils can alleviate migraine symptoms such as nausea, photophobia, and phonophobia by modulating neurotransmitter levels, reducing neurogenic inflammation, and promoting vascular relaxation. For instance, lavender oil's topical application to the temples has been associated with reflex actions that relax blood vessels and reduce pain perception, highlighting its unique mechanism of action [155]. ...
... Additionally, some essential oils are formulated into suitable pharmaceutical forms, like gels, for targeted application. Inhalation methods can accommodate flexible concentrations, ranging from 1% to 100%, depending on the enclosed space, making them adaptable to individual needs [155]. ...
Background: Migraine, a complex neurological condition, poses significant challenges for both sufferers and healthcare providers. While prescription medications play a vital role in managing migraine attacks, the quest for natural, non-pharmacological alternatives has garnered increasing interest. This review explores the efficacy and safety of natural supplements as treatments for migraine relief, comparing them with conventional prescription medications. Methods: The review delves into herbal supplements, clinical studies on natural remedies, aromatherapy, dietary influences, and lifestyle modifications in the context of migraine management in several databases. Results: The findings shed light on the potential of natural supplements as complementary or alternative approaches to traditional migraine therapies, offering insights into a holistic and personalized treatment paradigm for migraine sufferers. Conclusions: Natural supplements have gained attention as potential treatments for migraine relief, often perceived as safer alternatives to conventional medications.
... This vasodilation leads to a potential migraine attack. 10 Calcitonin gene related peptides (CGRP) is a neuropeptide that can help to relax blood vessels. 10 Van Dongen et al., 11 discovered the cerebral spinal fluid and serum CGRP levels in patients with migraines was significantly higher than those in healthy subjects. ...
... 10 Calcitonin gene related peptides (CGRP) is a neuropeptide that can help to relax blood vessels. 10 Van Dongen et al., 11 discovered the cerebral spinal fluid and serum CGRP levels in patients with migraines was significantly higher than those in healthy subjects. CGRP activates specific G protein coupled receptors which activate adenylyl cyclase. ...
... With a lower level of calcium within the cell, calmodulin dependent myosin light chain kinase becomes inactivated. 10 This deactivation reduces the activation of adenosine triphosphate (ATP) leading to vasodilation 12 and may result in a migraine attack. ...
Neurological disorders are recognized as one of the leading causes of death and disability worldwide. Migraines are a neurological disorder that is often accompanied by symptoms such as pain, light and sound sensitivity, nausea, vomiting, and changes in vision. There are many challenges to managing episodic and chronic migraines. There are several non-modifiable and modifiable risk factors associated with migraine onset. Pharmacological management has been shown to be effective. Research has also shown that aromatherapy can have a positive impact on preventing and managing migraine headaches. The purpose of this mini review is to provide current data on migraines and to offer options beyond prescribed pharmaceutical medication to alleviate symptoms of this disorder. It is important to offer alternative preventative solutions to manage migraine disorders.
... The best treatment for relieving the symptoms of the disease is aromatherapy. Traditional Chinese Medicine Aromatherapy is a monograph that indicates the efficacy of aromatic plants and their application in the treatment of different diseases [141]. Based on a single-blind study assessing the effectiveness of the topical usage of lavender oil on migraine, 47 patients with migraine at the beginning of attacks, were administrated with two to three drops of a placebo solution (liquid paraffin) or lavender oil rubbed onto their upper lip followed by inhalation the vapor for 15 min [142]. ...
... According to the results reported by Koto et al. (2006), rabbit carotid arteries were dilated by lavender [146]. Arginine nitrate, as a nitric oxide synthase (NOS) inhibitor, and 1H- [1,2,4] oxadiazole [4,3-α] quinoxaline-1-one, as the guanylyl cyclase inhibitor, have relaxation effects [141]. Shin et al. (2018) also found that in diabetic rats, the isolated aortic vasodilation caused by stress from ACh increased following an intraperitoneal injection of a low concentration of LA [147] (Fig. 5). ...
... Accordingly, LA may have an anti-migraine effect via inhibiting neurogenic inflammation and balancing vasomotor impairments. Therefore, more studies on plant essential oils are needed to develop novel anti-migraine agents [141]. A study found that using a 1:1 combination of essential oils from Lavandula angustifolia and Citrus bergamia (0.1 mL of 100% Lavandula angustifolia +0.1 mL of 100% Citrus bergamia) for 28 days effectively improved the quality of life, particularly among nurses working in emergency and critical care units during the intervention period [148]. ...
Neurological diseases affect the nervous system, including the brain, spinal cord, cranial nerves, nerve roots, autonomic nervous system, neuromuscular junctions, and muscles. Herbal medicine has long been used to cure these diseases. One of these plants is lavender, which is composed of various compounds, including terpenes, such as linalool, limonene, triterpenes, linalyl acetate, alcohols, ketones, polyphenols, coumarins, cineole, and flavonoids. In this review, the literature was searched using scientific search engines and databases (Google Scholar, Science Direct, Scopus, and PubMed) for papers published between 1982 and 2020 via keywords, including review, lavender, and neurological disorders. This plant exerts its healing effect on many diseases, such as anxiety and depression through an inhibitory effect on GABA. The anti-inflammatory effects of this plant have also been documented. It improves depression by regulating glutamate receptors and inhibiting calcium channels and serotonergic factors, such as SERT. Its antiepileptic mechanism is due to an increase in the inhibitory effect of GABA and potassium current and a decrease in sodium current. Therefore, many vegetable oils are also used in herbal medicine. In this review, the healing effect of lavender on several neurological disorders, including epilepsy, depression, anxiety, migraine, and Alzheimer's disease was investigated. All findings strongly support the traditional uses of lavender. More clinical studies are needed to investigate the effect of the plants' pharmacological active constituents on the treatment of life-threatening diseases in humans. The limitations of this study are the low quality and the limited number of clinical studies. Different administration methods of lavender are one of the limitations of this review.
... 1) Migraine is characterized by pulsatile pain on one or both sides of the head as well as other symptoms such as photophobia, phonophobia, nausea, and vomiting. 2) According to the International Classification of Headache Disorders, third edition, a migraine should comprise at least five attacks over the course of a lifetime, last 4-72 hours, and have at least two of the following characteristics: unilateral location, pulsating/throbbing quality, moderate to severe intensity, aggravation by/avoidance of routine physical activity, nausea and/or vomiting, photophobia, and phonophobia. 3) Despite the use of pharmacological medications for migraine headache treatment, the use of non-pharmacological therapy to alleviate migraine headache symptoms is growing and underestimated. ...
... Some oils can also reduce the symptoms of photophobia, phonophobia, nausea, and vomiting. 2) A systematic review of the alternative therapies used in headache treatment was published by Lopresti et al. 6) ; however, no meta-analysis was performed. This review includes all types of herbal treatments used for migraine headaches, including essential oils. ...
Alternative and complementary medicines are widely used to treat migraine headaches. This review aimed to determine the effectiveness of essential oils as an alternative treatment approach. A structured search was conducted to identify randomized trials comparing essential oils with a placebo for migraine headaches, using databases (MEDLINE and CENTRAL) to search for articles published between 1966 and 2021. We included trials involving adult males and females diagnosed with migraine headaches according to the International Headache Society. The outcomes included number of attacks, headache severity, associated symptoms, number of days of limited activity, headache duration, use of analgesics, and adverse effects. Seven trials were included with a total of 558 participants. No difference was observed in the number of migraine headache attacks compared to placebo (mean difference [MD], -1.34; 95% confidence interval [CI], -3.31 to 0.64; I2=94%; P=0.190; four trials, 242 participants; moderatequality evidence). There was no difference in this outcome between the essential oils treated group and the placebo (MD, -0.38; 95% CI, -1.76 to 0.99; I2 statistics=86%; P=0.580; five trials, 240 participants; moderate-quality evidence). We found no significant difference between the use of essential oils and placebo in managing migraine headaches.
... Aromatherapy is the most comfortable and pleasant all-natural therapy with effcient and rapid effect against migraine symptoms. Application of essential oils for F o r P e r s o n a l U s e O n l y migraines has been evidenced in traditional Chinese medicine (Yuan et al. 2021). Migraines can be treated by using different essential oils from different plants: chamomile, Angelicae dahuricae Radix, Chuanxiong rhizome, etc. ...
... Some of them produce relief from nausea, vomiting, photophobia and other symptoms. This effect is different in different people with different doses (Niazi et al. 2017;Sasannejad et al. 2012;Yuan et al. 2021). Essential oils from Lavandula angustifolia Mill (dried fower heads and aerial foliage) (Sasannejad et al. 2012), garlic (bulb) (Marschollek et al. 2017 (Ahmadifard et al. 2020) are also used to treat migraines. ...
Aromatherapy is a rapidly growing, alternative and integrative therapy that can replace the conventional medical treatment with essential oils for managing conditions like depression, anxiety, pain, nausea, vomiting, indigestion, joint pains, sleep disturbance, and muscle tension, and also to enhance physical and psychological wellbeing. The essential oils, which are derived from different plant parts like leaves, flowers, fruits, stems, roots, bark, grass etc., are used for the aromatherapy. Usually the oils are applied topically for massage or through inhalation. Olfactory stimulation of aromatherapy can result in immediate reduction in pain and other physiological parameters like blood pressure, pulse, skin temperature and activity of brain. Nowadays, aromatherapy is the most attractive therapy for treating illness and for enhancing wellbeing because of less side effects and low cost, so the use of essential oils for aromatherapy has increased in recent years. In the scientific literature, there is an increasing amount of evidence suggesting that there may be beneficial effects in treating a number of health conditions with plant essential oils, alone or in combination with other therapies. This review explores the latest information on literature of plants and their essential oils used in aromatherapy.
... Essential oils have well-established antibacterial, antibiotic, and antiviral properties, and are also believed to be beneficial for use in treating Alzheimer's disease, cardiovascular disease, cancer, migraine [15], and pain during pregnancy [16,17]. The use of essential In plants, terpenes are derived from two universal five-carbon precursors, isopentenyl pyrophosphate and C5-dimethylallylpyrophosphate [7]. ...
... Essential oils have well-established antibacterial, antibiotic, and antiviral properties, and are also believed to be beneficial for use in treating Alzheimer's disease, cardiovascular disease, cancer, migraine [15], and pain during pregnancy [16,17]. The use of essential oils as antioxidants in the preservation of various foods is gaining in popularity [18]. ...
Successful management of the synthesis of secondary metabolites of essential oil plants is the basis for the economic growth of the essential oil industry. Against the backdrop of a growing global population and a decrease in land available for cultivation, simple and effective ways to increase the content of certain components in essential oils are becoming increasingly important. Selection is no longer keeping pace with market needs, which stimulates the search for faster methods to control the biosynthesis of secondary metabolites. In this article, using the genera Lavandula and Mentha as examples, we consider the prospects for use of antisense oligonucleotides (ASO), oligoilators, to rapidly increase the concentration of valuable components in essential oil and its yield. This article discusses the use of unmodified ASOs as regulators of a plant’s secondary metabolism to increase the synthesis of individual valuable components, presenting a completely new way to increase the yield of valuable substances based on unique nucleotide sequences. The proposed approach is effective, affordable, safe, and significantly reduces the time needed to obtain plants that synthesize the required concentrations of target substances. Oligoilators can be used with oligonucleotide insecticides (olinscides) in complex formulations used for green agriculture. Further investigation is needed to determine maximum economic efficiency for this approach.
... Although the primary mechanism of action of lavender aromatherapy is unknown, according to an analysis of clinical trial results in our research, it can make women in labor experience less pain during labor (Karo Hy, 2017). Based on previous research on the psychological and physiological benefits of EOs, aromatherapy controls human mood and reduces anxiety without altering physiological circumstances (Yuan R, 2021) This result is also the same as Tabata's Research (2020) showing the results that aromatherapy, as a complementary and alternative quality, can help relieve maternal anxiety and pain during Labor Pain felt by the mother during labor is a physiological thing but if it hurts labor is left alone it will have an impact to things that are not desirable like the first stage elongated. Aromatherapy Lavender is a natural treatment method using essential oils originating from lavender plants with certain dilution. ...
As many as 810 mothers die every day from diseases/complications related to pregnancy and childbirth in 2017 and the Maternal Mortality Rate (MMR) is still high in Indonesia. In the process of childbirth there is pain that is physiological in nature but can have bad consequences if not handled properly. Labor pain can be treated in non-pharmacological ways such as aromatherapy. Objective: to determine the effect of giving lavender aromatherapy to pain in the first stage of labor in mothers. Method : pretest-posttest experiment with control group design. The experimental group was given lavender aromatherapy, the control group was not intervention. The study was conducted in to the Midwife Practice Mandiri Nini and Ria at the in June - July 2022. The sample consisted 38 Mother Maternity first Stage. Data were analyzed using paired sample t test and non-parametric Mann Whitney test. The results : the p value of each characteristic in the experimental group and the group control shows a number > 0.05. This means that the characteristics of respondents between groups are equal or homogeneous. Bivariat : the value of P 0.001 in the experimental group and 0.002 in the control group. This is that the lavender aromatherapy for the scale of labor pain. The Non-Parametric Mann Whitney Test results obtained a p value of 0.004 (p <0.05), it can be concluded that there are differences in decreasing labor pain scale in the experimental group and the control group.
... Minyak atsiri banyak dikenal karena aroma khas dan berbagai aktivitas farmakologi yang dimilikinya. Minyak atsiri telah terbukti dapat digunakan sebagai swamedikasi untuk pengobatan alternatif nyeri, migrain, dan antikecemasan (Gong et al., 2020;Yuan et al., 2021;Dewanjee et al., 2023). selain itu, stimulasi sensorik yang diberikan oleh minyak atsiri melalui penciuman dan sentuhan dapat secara signifikan meningkatkan kualitas hidup pasien (Lakhan et al., 2016). ...
Aromaterapi merupakan salah satu terapi komplementer yang memanfaatkan minyak atsiri sebagai komponen aktif. Meskipun memiliki banyak manfaat, penggunaan minyak atsiri yang tidak tepat dapat menimbulkan risiko kesehatan. Pengabdian ini bertujuan untuk meningkatkan pemahaman masyarakat, khususnya anggota Pemberdayaan dan Kesejahteraan Keluarga (PKK), dalam pemanfaatan minyak atsiri sebagai aromaterapi untuk pengobatan mandiri di rumah. Kegiatan edukasi dan pelatihan dilaksanakan di tiga kecamatan di Kota dan Kabupaten Malang dengan melibatkan 50 orang peserta dengan latar belakang pendidikan dan pekerjaan yang beragam. Melalui penyuluhan dan praktik langsung dalam pembuatan minyak aromaterapi, peserta diberikan informasi tentang penggunaan yang aman dan efektif, serta potensi manfaat dan risiko dari penggunaan minyak atsiri. Pengetahuan peserta dinilai sebelum dan sesudah kegiatan melalui pre-test dan post-test. Hasil analisis menunjukkan peningkatan signifikan dalam pemahaman peserta tentang pemanfaatan minyak atsiri sebagai aromaterapi untuk pengobatan mandiri di rumah (P< 0,05). Dengan demikian, pengabdian ini dapat membantu komunitas dalam memahami manfaat aromaterapi sebagai alternatif pengobatan mandiri yang aman dan efektif di rumah.
... Different plant essential oils have been experimented with in numerous clinical trials for their efficiency as anti-migraine treatments (Murtey et al., 2023), and their mechanism of action has been widely reviewed (Yuan et al., 2020). However, few studies have investigated the usage patterns of these agents among the general population. ...
Migraine is a debilitating disease with a complex pathophysiology and multiple risk factors. Due to the limited efficacy and tolerability of available pharmacologic treatments, patients often seek complementary and alternative therapies like aromatherapy, which has shown promising results in various clinical trials. This survey investigates the usage patterns of essential oils among migraine patients and their knowledge of proper usage methods and associated side effects. A cross-sectional descriptive study was conducted over nine months (December 2022 to August 2023) among migraine patients using a semi-structured electronic questionnaire analyzed with Microsoft Excel. Most participants (83.44%) were aged 25 to 64, predominantly female (83%). Among them, 42.75% had suffered from migraines for 5 to 15 years, with 61.19% reporting significant life impact due to the condition. Over half opted for alternative treatments; aromatherapy was used by 61%, with essential oils such as Mentha piperita, Lavandula angustifolia, Eucalyptus globulus, Cinnamomum camphora, and Nigella damascena being most cited. Notably, 55% reported symptom improvement after use. Aromatherapy shows potential as a complementary approach for managing migraine symptoms. However, the lack of awareness regarding proper usage and safety highlights the need for patient education and further clinical studies to establish its efficacy and ensure safe practices.
... Aromatherapy involves the therapeutic application of essential oils derived from plants to enhance physical, emotional, and spiritual wellbeing. The essential oil industry has experienced significant growth, particularly through convenient sales channels and its emphasis on addressing specific chronic conditions, such as cancer [44,45], insomnia [46], and migraine [47]. Recent reviews suggest that aromatherapy may offer health benefits, including improved sleep quality and reduced fatigue, anxiety, symptoms of restless legs, and arteriovenous fistula puncture pain in patients undergoing HD [48]. ...
Background
Despite the paucity of scientific evidence, complementary and alternative medicine (CAM) is widely used for the prevention and treatment of chronic illness, holistic care, and counteracting the adverse effects of conventional therapies. This study aims to determine the prevalence of CAM use and its associated factors among patients undergoing hemodialysis (HD) in Taiwan.
Methods
This quantitative study was conducted from August 2022 to July 2024 in the HD unit at Kaohsiung Chang Gung Memorial Hospital in Taiwan. Face-to-face questionnaire-based interviews were held with 154 of 163 eligible patients (response rate, 94.5%) at the bedside during HD. The completed questionnaires were entered into a secure computer database. Data was performed by descriptive analysis, Chi-square, and Fisher tests.
Results
More than half of the patients were CAM users (n = 86; 56%), and women was associated with significantly more usage of CAM. Fifty-six CAM users took Chinese herbal medicine (CHM), 52.3% (n = 45) used dietary supplements, and 19.8% (n = 17) used acupuncture. The benefit in the effectiveness of CAM was the main reason for use, the need of CAM to improve the well-being and HD-related complication was high. 32.7% of patients had used CAM based on recommendation from their family and friends. More than one-third (33.7%) of patients did not disclose their use of CAM to their doctors, most of them think it is unnecessary.
Conclusions
The use of CAM by patients with maintenance HD was relatively frequent. Of these, most used CHM, of which are shown to the trend into routine HD care is inevitable by high coverage and utilization in Taiwanese national health insurance system. These findings indicate that it is important for health care providers working in dialysis to assess CAM use.
... Orally administering PEOs to animals also induces anxiety and discomfort. This results in abnormal behaviors like smearing and grabbing, which negatively impact the outcomes (Yuan et al., 2021). On day 7 of the pathogen-infected mice model of wounds, Mentha piperita L. EO treatment bigger IL-1β levels in the diseased wound tissue while lowering the levels of fibroblast growth factor-2 (FGF2) and vascular endothelial growth factor (VEGF). ...
Essential oils (EOs) are complex combinations of aromatic compounds found in various plant species, renowned for their therapeutic properties and potential as agents for inflammation reduction. Originating from the plant's secretory organs, EOs are extracted through pressing or distillation methods, offering unique energetic and therapeutic benefits. The chemical composition of EOs, comprising terpenes, phenylpropanoids, and other volatile compounds, contributes to their diverse medicinal properties. Inflammation, the body's response to tissue damage or infection, is a complex biological method regulated by intricate indicating pathways and inflammatory mediators. Essential oils have shown promise in modulating inflammatory pathways, including NF-κB, MAPK, and JAK-STAT, thereby mitigating the release of pro-inflammatory cytokines and reducing tissue damage. Topical use of certain essential oils, such as chamomile, lavender, and eucalyptus oils, has demonstrated anti-inflammatory effects in preclinical studies, offering potential therapeutic benefits for conditions like rheumatism, arthritis, dermatitis, and eczema. Experimental models, both in vivo and in vitro, have provided insights into the mechanisms underlying the anti-inflammatory properties of essential oils, highlighting their potential as novel therapeutic agents. However, while preclinical evidence is promising, further clinical trials are warranted to assess the efficacy and safety of essential oils in human therapy. Clinical studies have shown promising results in conditions such as chronic periodontitis and dental plaque accumulation, but more research is needed to explain the precise tools of action and determine optimal dosage regimens. In conclusion, essential oils hold significant potential as natural remedies for inflammation-related disorders, but their therapeutic utility requires further exploration through rigorous clinical investigation.
... Due to partial efficacy and safety profile of the current pharmacological options for migraine treatment, alternative or adjunct interventions to enhance treatment outcomes are clearly warranted. In this sense, there is increasing evidence that essential oils from several plants may provide benefit for migraine patients (9,10). The essential oil of Mentha piperita L. (peppermint) is one of the most used essential oils in the pharmaceutical and cosmetics industries. ...
Migraine is a severe and disabling neurological disorder characterized by headache, photophobia, phonophobia, nausea and vomiting. It is considered the top cause of years lived with disability between the ages of 15–49, being two to three times more common in women than in men. Pharmacological treatment of migraine has advanced in the past years but is still considered unsatisfactory for a significant number of patients. There is growing evidence that essential oils may provide benefit for migraineurs. Herein it was tested the hypothesis that peppermint essential oil (Mentha piperita L.) could reduce migraine-related responses in rats. The model consisted in the injection of calcitonin-gene-related peptide (CGRP) in the trigeminal ganglion (TG) of female rats to induce the development of immediate periorbital cutaneous allodynia and late photosensitivity (24 h after CGRP). Inhalation of the peppermint essential oil during 15 minutes before CGRP injection in the TG did not reduce periorbital allodynia and photosensitivity of female rats. However, when the exposure occurred after CGRP injection, peppermint essential oil caused a significant reduction in both parameters. Likewise, intranasal application of menthol, a major component of peppermint essential oil caused a significant reduction of periorbital allodynia induced by CGRP. In conclusion, peppermint essential oil and menthol may represent a safe, low cost and noninvasive adjuvant abortive therapy for headache pain in migraine patients. However, further high-quality clinical studies are clearly warranted to determine efficacy, safety and to establish their best treatment regimen.
... In this investigation, as revealed in Table 2, the acidity value, the density value, the refractive index and the moisture and volatile compound level of LJEO were 0.15 KOH/g, 0.34 g/cm 3 , 1.53, and 3.87 g/cm 3 , respec-tively. The determination of these physical-chemical properties of LJEO might provide potential information for the development of essential oils in the near future, especially in aromatherapy 27,28 . ...
The essential oil extracted from the flower buds of Lonicerae japonicae (LJEO) was employed in the high-temperature (65℃) accelerated preservation of sunflower oil. In the present investigation, the addition of the essential oil at a concentration of 800 ppm significantly inhibited the decrease in the oxidative stability of sunflower oil. This positive effect was achieved by significantly hindering the reduction in acidity value (AV), peroxide value (PV), ρ-anisidine value (AnV), the total oxidation value (TOTOX) (p < 0.01), and the levels of thiobarbituric acid reactive substance (TBARS), the absorbance at 232/268 nm (K232/K268) and total polar compounds (TPC) (p < 0.01). Besides, it also significantly enhances the sensory attributes of Maye, including taste, flavor, and appearance, improving its overall acceptability through the addition of certain potential fragrance molecules (p < 0.01). Furthermore, one of the primary chemical compounds in LJEO, eugenol, has demonstrated significant natural antioxidant properties in the traditional deep-frying procedure for the product, Maye. Consequently, together with eugenol, the essential oil LJEO could be employed as a possible effective antioxidant for the typical long-term preservation and even the traditional deep-frying procedures, and developed as effective antioxidant extracted from plants for the whole food industry.
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... Hal ini karena tanaman kayu putih memiliki manfaat dalam bidang kehutanan (kayu, bahan bakar, dan kertas), lingkungan (pengendalian erosi air dan angin), kesehatan (obat, aromatherapy), seni serta kerajinan (Devi et al., 2015). Sejalan dengan itu, beberapa negara menggunakan kayu putih dengan potensi manfaat sebagai industri pulp, wewangian, kosmetik, makanan, minuman, aromaterapi, dan fitoterapi (Farrar & Farrar, 2020;Gong et al., 2020;Her & Cho, 2021;Yuan et al., 2021). Selain itu, tanaman kayu putih juga menghasilkan biomassa dalam jumlah besar sekaligus menyerap karbon dioksida secara efektif dan mampu menghasilkan oksigen (Vecchio et al., 2016). ...
Abstrak: Aroma minyak kayu putih sangat bermanfaat bagi kesehatan. Khasiat ini belum dioptimalkan di wilayah Pulau Buru sebagai penghasil tanaman kayu putih terbesar di Maluku melalui diversifikasi produk. Sehingga pengabdian ini bertujuan untuk meningkatkan pemahaman dan melatih keterampilan mitra dalam membuat aromaterapi. Metode yang digunakan yaitu pelatihan kepada 10 peserta melalui materi, simulasi dan tanya jawab terkait pembuatan aromaterapi, pendampingan secara langsung maupun video termasuk label produk dan pemasaran online, serta monitoring evaluasi yang melibatkan pemerintah desa kepada 10 orang pekerja ketel di Desa Wamlana, Kabupaten Buru, Provinsi Maluku. Hasil yang telah dicapai dalam kegiatan ini yaitu nilai pre-test meningkat dari 81 menjadi 92 pada post-test dengan hasil observasi praktik mandiri 94. Selain itu, produk aromaterapi yang siap dipasarkan juga telah tersedia dengan kemasan produk. Peningkatan pengetahuan dan hasil observasi dengan kategori baik menunjukkan peserta sudah memahami diversifikasi produk aromaterapi dan bagaimana komposisi pembuatannya. Sehingga pengembangan produk perlu dilakukan evaluasi monitoring agar tetap memberi kontribusi dan dampak berkelanjutan.Abstract: The health benefits of eucalyptus oil are significant, yet these advantages remain underutilized in the Buru Island region, which stands as the largest producer of eucalyptus plants in Maluku. The potential for product diversification has not been fully explored. This service is designed to address this gap by training partners to diversity their products, particularly focusing on aromatherapy. The training method involved instructing 10 participants through materials, simulations, and a Q&A session related to aromatherapy production. The training included both direct and video assistance, encompassing aspects such as product labelling and online marketing. Evaluation monitoring, involving the village government, was conducted for 10 boiler workers in Wamlana Village, Buru Regency, Maluku Province. The results of this activity were noteworthy. The pre-test scores increased from 81 to 92 in the post-test, with an independent practice observation yielding a score of 94. Additionally, ready-to-market aromatherapy products, complete with packaging, were successfully developed. The improvement in knowledge and observation, falling into the ‘good’ category, indicates that participant now comprehend the diversification of aromatherapy products and the production process. To ensure sustainability and ongoing positive impact, it is crucial to monitor and evaluate product development continually. This will help maintain a steady contribution to the community and beyond.
... The essential oil originating from Radix Angelica Sinensis showed analgesic effects and blood circulation improvements by adjusting glycine and arachidonic acid levels (Wang et al., 2016;Li et al., 2017;Hua et al., 2019). In addition, the volatile oil derived from Chuanxiong Rhizoma also exhibited anti-migraine effects by relieving pain behaviors (Guo-Jing et al., 2020;Yuan et al., 2021). Nevertheless, many active substances in essential oils with poor water solubility and high volatilization are prone to be unstable because of large surface areas of oil droplets available for oxidation, which may be avoided by nanoparticle encapsulation (Hou et al., 2022). ...
Background: Migraine is a common neurovascular disorder with typical throbbing and unilateral headaches, causing a considerable healthcare burden on the global economy. This research aims to prepare chitosan-alginate (CS-AL) nanoparticles (NPs) containing Foshousan oil (FSSO) and investigate its potential therapeutic effects on the treatment of migraine.
Methods: FSSO-loaded CS-AL NPs were prepared by using the single emulsion solvent evaporation method. Lipopolysaccharide (LPS)-stimulated BV-2 cells and nitroglycerin (NTG)-induced migraine mice were further used to explore anti-migraine activities and potential mechanisms of this botanical drug.
Results: FSSO-loaded CS-AL NPs (212.1 ± 5.2 nm, 45.1 ± 6.2 mV) had a well-defined spherical shape with prolonged drug release and good storage within 4 weeks. FSSO and FSSO-loaded CS-AL NPs (5, 10, and 15 μg/mL) showed anti-inflammatory activities in LPS-treated BV-2 cells via reducing the levels of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and nitric oxide (NO), but elevating interleukin-10 (IL-10) expressions. Moreover, FSSO-loaded CS-AL NPs (52 and 104 mg/kg) raised pain thresholds against the hot stimulus and decreased acetic acid-induced writhing frequency and foot-licking duration in NTG-induced migraine mice. Compared with the model group, calcitonin gene-related peptide (CGRP) and NO levels were downregulated, but 5-hydroxytryptamine (5-HT) and endothelin (ET) levels were upregulated along with rebalanced ET/NO ratio, and vasomotor dysfunction was alleviated by promoting cerebral blood flow (CBF) in the FSSO-loaded CS-AL NPs (104 mg/kg) group.
Conclusion: FSSO-loaded CS-AL NPs could attenuate migraine via inhibiting neuroinflammation in LPS-stimulated BV-2 cells and regulating vasoactive substances in NTG-induced migraine mice. These findings suggest that the FSS formula may be exploited as new phytotherapy for treating migraine.
... The use of plants in medicine and cosmetics has increased dramatically with the rapid growth of physical therapy 26 . Natural ingredients derived from plants are getting a lot of attention in the cosmetic industry 27 . ...
Sunflower oil (SFO) is faced with serious oxidation problems during the deep-frying of Chinese Maye, and the search for natural antioxidants has become a focus of scientific research due to the potential toxicity of synthetic antioxidants. In the present study, the Foeniculum vulgare Mill. essential oil (FVEO), tert-butylhydroquinone (TBHQ) were added to SFO for a 30 h deep frying experiment and the results showed that FVEO added to sunflower oil at 1 g/kg was similar to that of TBHQ-0.01 g/kg, and FVEO-1.5 g/kg would promote the oxidation of SFO. FVEO to sunflower oil also prominently restrained the decrease of the sensory properties of the fried product, Chinese Maye, including appearance, taste, flavor and overall acceptance by 24.2%, 20.2%, 46.1% and 56.0% (p < 0.01 or p < 0.05), respectively. The results indicated that FVEO could be used as a natural antioxidant to replace TBHQ in the deep-frying process of SFO, but further research is needed on the key antioxidant constituent of FVEO.
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... The essential oils derived from aromatic plants exert their analgesic effects via inhibiting tissue inflammation and pain sensitization, and can affect vasomotor activity. Therefore, essential oils are effective in reducing the pain of patients by stimulating the brain to release pain-relieving neurotransmitters as well as their anti-inflammatory effects [43]. Aromatherapy could be a pleasant agent for promoting regulators of sympathetic nervous system dysfunctions and unpleasant feelings [44]. ...
Background: Untreated cardiovascular disease (CVD) can commonly cause disability and morbidity and increase the mortality risk.
Objective: This systematic review and meta-analysis study aimed to investigate the pain-relieving effects of aromatherapy with medicinal plants on patients with cardiovascular diseases.
Methods: This meta-analysis followed PRISMA guidelines. Several keywords were explored using an extensive search of databases, including PubMed, Web of Science (ISI), EMBASE, and Scopus, on May 15, 2022. In addition, an excel form was designed for recording the data of the RCT studies. Standardized mean difference (SMD) and their 95% confidence intervals (CI) were used to estimate the overall effect size. The Cochran Q test and the statistic I2 were used to evaluate the heterogeneity of studies. Lastly, Egger's and Begg's tests were used to assess potential publication bias.
Results: We included studies examining the effect of inhalation aromatherapy on pain in patients with CVD after 5 minutes (five papers) and 15-30 minutes (six papers) of intervention. The results showed a significant decrease in pain in the intervention group compared to the control group after 5 minutes (SMD = -2.25, 95% CI = -3.21 to -1.29, P < 0.001) and after 15-30 minutes (SMD = -3.22, 95% CI = - 4.41 to -2.03, P < 0.001) of intervention in CVD patients. No publication bias was observed related to the association between inhalation aromatherapy and pain relief.
Conclusion: In CVD patients, inhalation aromatherapy could significantly reduce pain severity and can be used as a complementary medicine for pain reduction.
... However, more clinical studies are still needed to confirm the potential of grape seed extract in reducing chronic orofacial pain. Aromatherapy has presented analgesic effects in migraine 56 and muscular TMD 57 . In practice, essential oils can be used topically while massaging the pain are and vaporized to be inhaled. ...
... However, more clinical studies are still needed to confirm the potential of grape seed extract in reducing chronic orofacial pain. Aromatherapy has presented analgesic effects in migraine 56 and muscular TMD 57 . In practice, essential oils can be used topically while massaging the pain are and vaporized to be inhaled. ...
BACKGROUND AND OBJECTIVES
Faced with the difficulty of treating chronic orofacial pain and seeking an approach that aims at the health and well-being of the patient in a broader way, cannabinoid therapy appears as an adjunct to pharmacological approaches.
CONTENTS
Cannabinoid therapy generates analgesia through the activation of the endocannabinoid system, as well as the use of palmitoylethanolamide (PEA), curcumin, grape seed extract, aromatherapy, acupuncture, laser therapy and the practice of physical exercise. In this way, these therapies allow a reduction in the use of analgesic drugs.
CONCLUSION
Cannabinoid therapy is part of this integrative approach and the combination of cannabinoids with other forms of activation of the endocannabinoid system contributes to a better therapeutic outcome and a better quality of life for countless patients suffering from chronic orofacial pain.
Keywords:
Cannabidiol; Cannabis; Chronic pain; Endocannabinoids; Facial pain; Integrative dentistry
... Moreover, menthol-the main component of PO-reportedly interferes with TRPA1 channels, reducing skin pain, hypersensitivity, and neurogenic in ammation [48]. Activation of TRPA1 channels is associated with pain and development of in ammation through increased NO levels and Ca 2+ concentration, which are related to the release of the relevant factors [49]. In addition, Lmenthone inhibits the release of in ammatory cytokines, thus reducing their levels in vivo [50]. ...
Although the introduction of glycerosomes have enriched strategies for efficient transdermal drug delivery, the inclusion of cholesterol as a membrane stabilizer has limited their clinical application. The current study describes the development and optimization of a new type of glycerosome (S-glycerosome) that is formed in glycerol solution with β-sitosterol as the stabilizer. Moreover, the transdermal permeation properties of lappaconitine (LA)-loaded S-glycerosomes and peppermint oil (PO)-mediated S-glycerosomes (PO-S-glycerosomes) are evaluated, and the lipid alterations in the stratum corneum are analyzed via lipidomics. Results show that the LA-loaded S-glycerosomes have a mean size of 145.3 ± 7.81 nm and encapsulation efficiency of 73.14 ± 0.35%. Moreover, the addition of PO positively impacts transdermal flux, peaking at 0.4% (w/v) PO. Tracing of the fluorescent probe P4 further revealed that PO-S-glycerosomes penetrate deeper into the skin than S-glycerosomes and conventional liposomes. Additionally, treatment with PO-S-glycerosomes alters the isoform type, number, and composition of sphingolipids, glycerophospholipids, glycerolipids, and fatty acids in the stratum corneum, with the most notable effect observed for ceramides, the main component of sphingolipids. Furthermore, the administration of PO-S-glycerosomes improves the treatment efficacy of xylene-induced inflammation in mice. Collectively, these findings demonstrate the feasibility of β-sitosterol as a stabilizer in glycerosomes. Additionally, the inclusion of PO improves the transdermal permeation of S-glycerosomes, potentially by altering the stratum corneum lipids.
... Essential oils have well-established antibacterial, antibiotic, and antiviral properties, and are also believed to be beneficial for use in treating Alzheimer's disease, cardiovascular disease, cancer, migraine [13], and pain during pregnancy [14,15]. The use of essential oils as antioxidants in the preservation of various foods is gaining in popularity [16]. ...
Successful management of the synthesis of secondary metabolites of essential oil plants is the basis for the economic growth of the essential oil industry. Against the backdrop of a growing global population and a decrease in land available for cultivation, simple and effective ways to increase the content of certain components in essential oils are becoming increasingly important. Selection is no longer keeping pace with market needs, which stimulates the search for faster methods to control the biosynthesis of secondary metabolites. In this article, using the genus Lavandula as an example, we will consider the prospects for use of antisense oligonucleotides (ASO), oligoilators, to rapidly increase the concentration of valuable components in essential oil. This article discusses the use of unmodified ASOs as regulators of plant secondary metabolism to increase the synthesis of individual valuable components, presenting a completely new way to increase the yield of valuable substances based on unique nucleotide sequences. The proposed approach is effective, affordable, safe, and also significantly reduces the time needed to obtain plants that synthesize the required concentrations of target substances. Oligoilators can the used along with oligonucleotide insecticides in complex formulations used for green agriculture. Further investigation is needed to determine maximum economic efficiency of this approach.
... First, after inhaling essential oils, the nasal olfactory nerve carries the scent information to the rhinencephalon (the olfactory area of the brain), which can trigger the rapid release of neurotransmitters (such as dopamine and 5-HT) that regulate the nervous system. This can induce physiological and mental states of relaxation, pleasure, and happiness [1][2][3][4]. Second, after inhaling essential oils, essential oil molecules can enter the nasal mucosa and lungs. ...
This study evaluated the effects of essential oils mainly containing Eupatorium fortune Turcz (EFCO, E. fortune Turcz extract, water calamus extract, grapefruit extract, lavender extract, mixed in the ratio of 6:1:1:1:0.1 by volume) on heart rate variability (HRV), forced vital capacity (FVC), and salivary hormones in 33 scientific researchers. The experimental design was a quasi‐experimental study with pre‐ and post‐testing and no control group. Subjects were tested for four immediate indicators before and after essential oils inhalation, for 30 s before each meal for the next 30 days, and for body mass index (BMI) after 30 days. For immediate effects, we observed significant increases in HRV (31%), spirometry (12%) and salivary oxytocin (26%), and a decrease in salivary cortisol (4.5%). BMI decreased by 1% after 1 month of intervention. Based on the observed changes in physiological parameters, EFCO helped to reduce stress, improve exercise performance and mood, and even promote weight loss. © 2022 Institute of Electrical Engineers of Japan. Published by Wiley Periodicals LLC.
Essential oils (EOs) are complex mixtures of volatile compounds, primarily terpenoids and phenolic constituents, derived from plants. They have been widely studied for their diverse biological activities, including antibacterial, antifungal, antiviral, anticancer, and anti-inflammatory effects, among others. These bioactivities are attributed to the unique chemical composition of EOs, which enables multi-targeted modes of action such as disruption of microbial cell membranes, inhibition of spore germination, and modulation of inflammatory pathways. Their potential as alternatives to conventional antimicrobial therapies has gained attention, particularly in addressing antimicrobial resistance. Additionally, EOs exhibit significant antioxidant and antimicrobial properties, contributing to food preservation by preventing spoilage and extending shelf life. In agriculture, their roles in pest management and plant growth regulation highlight their sustainable applications. In conclusion, EOs present a promising avenue for sustainable applications in healthcare, food preservation, and agriculture, though further research is necessary to overcome challenges related to their variability and clinical validation.
This study examines the effects of lavender plants on fatigue levels and performance. The research started by randomly dividing 60 participants aged 18-25 into study and control groups. The Wingate Anaerobic Test was applied to the participants and the study group was administered a sauna filled with lavender. Data were collected and analyzed by measuring blood lactate levels. In all physiological characteristics examined, the differences between the control group and the study group before the study were found to be statistically insignificant. In both the study group and the control group, except for diastolic blood pressure, changes in all physiological characteristics and blood values according to measurement times (0, 1, 5 and 15 min) were found to be very significant (p
Essential oils (EOs) are volatile products derived from the secondary metabolism of plants with antioxidant, antimicrobial, and pesticidal properties. They have traditionally been used in medicine, cosmetics, and food additives. In agriculture, EOs stand out as natural alternatives for pest control, as they show biocidal, repellent, and antifeedant effects. However, they are highly volatile compounds and susceptible to oxidation, which has limited their use as pesticides. This has led to exploring micro- and nano-scale encapsulation to protect these compounds, improving their stability and allowing for a controlled release. Various encapsulation techniques exist, such as emulsification, ionic gelation, and complex coacervation. Nanoemulsions are useful in the food industry, while ionic gelation and complex coacervation offer high encapsulation efficiency. Materials such as chitosan, gelatin-gum-Arabic, and cyclodextrins are promising for agricultural applications, providing stability and the controlled release of EOs. Encapsulation technology is still under development but offers sustainable alternatives to conventional agrochemicals. This article reviews the potential of EOs in pest management and encapsulation techniques that enhance their efficacy.
In summary, neurodegenerative diseases are multifactorial disorders marked by the degeneration and eventual death of nerve cells, leading to structural and functional deterioration. Alzheimer’s, Parkinson’s, Huntington’s, Amyotrophic Lateral Sclerosis, and Multiple Sclerosis are notable examples of such diseases, impacting quality of life and often progressing rapidly. While there is currently no definitive cure for these conditions, treatment strategies focus on enhancing quality of life by slowing disease progression. However, chronic use of existing therapeutic interventions and medications can cause serious side effects. This situation has led patients to turn to alternative medicine practices.A prominent approach among complementary medicine practices is the use of medicinal plants with neuroprotective properties. These plants can aid in brain injury recovery and enhance learning and memory functions through the stimulation of new synapse formation. These plants containing phytochemicals may be effective in the developmental mechanisms of neurodegenerative diseases and may favourably affect the prognosis of the disease. Therefore, phytochemical, pharmacological and clinical research on medicinal plants may make promising contributions to the development of naturally derived drugs for neurodegenerative diseases.
The chemical components of natural fragrant plant extracts are of high complexity, and the strategies for quality control (QC) and further discovery of fragrance mechanisms still need to be further investigated. This study integrated the strategies and methods of untargeted metabolomics and chemometrics and statistical modeling to attain the goal. The techniques of reversed-phase and HILIC analysis of ultra-performance liquid chromatography-high-resolution mass spectrometry (UPLC-HRMS) were simultaneously used to collect data in both positive and negative ion modes. The pattern analysis of fingerprints and discovery of characteristic molecular markers for QC analysis were comprehensively employed to reach in-depth analysis of the quality variation and discovery of differential molecules among natural fragrant plant extracts. The former uses fingerprint technique to analyze their overall similarities and differences, and the latter comprehensively discovers molecular substances characterizing the chemical characteristics of fragrant extracts with the help of metabolomics and univariate and multivariate methods. The findings are expected to be used as the molecular markers in product manufacturing, sales, and consumption to achieve accurate quality control and recognition of targeted molecules for potential quality monitoring using spectroscopy techniques. In this work, 27 natural fragrant extracts were applied as examples, and their chemical components were comprehensively analyzed with discovery of markers for quality control. After data integration, 1178 molecules were annotated, and 267 differential metabolite molecules with the values of variable importance in the projection (VIP) larger than 1.0 were found. The results show that the method proposed in this work is of great significance for high-coverage analysis, QC marker discovery, and aroma mechanism elucidation, which has potential applications in the areas of food, cosmetics, pharmaceuticals, tobacco, and others.
Background: Intraoperative anxiety is a common problem when Monitored Anesthesia Care (MAC) is used instead of general anesthesia during minor surgical procedures such as port catheter placement. Nonpharmacological anxiolytics such as aromatherapy have been studied for their effects on preoperative anxiety, but no placebo-controlled study of aromatherapy during surgeries under MAC has yet been performed. Methods: After IRB approval, 70 patients were randomized 1:1 to receive either a lavender/peppermint aromatherapy patch (Elequil Aromatabs®; Beekley Corporation) or a matching placebo patch. The primary outcome, time to readiness for discharge from postoperative acute care units (PACU; min), was assessed every 15 min until a modified postanesthesia recovery score for ambulatory patients (PARSAP) score of 18 or higher was reached. In the preoperative holding area, the assigned patch/placebo was activated and affixed to a folded towel placed aside the subject's head, contralateral to the side of the planned surgery. The towel and patch/placebo were discarded when the subject left the operating room (OR). Results: No difference was found between the treatment and placebo groups on the primary outcome of time to discharge readiness (mean [standard deviation, SD]: 82 [15] vs. 89 [21] min, respectively, p = 0.131). No difference was found between the treatment and placebo groups on the secondary outcomes of intraoperative midazolam dose, intraoperative opioid dose, intraoperative ondansetron dose, or intraoperative promethazine dose. No difference was found between the treatment and placebo groups in the proportion of subjects requiring rescue postoperative nausea and vomiting (PONV) medication in the PACU or the proportion of subjects requiring opioids in the PACU. No difference was found between the treatment and placebo groups in pain intensity in PACU, average PONV score in PACU, or patient satisfaction in PACU. PACU patient satisfaction was high for both the patch and placebo groups (35/35 [100%] vs. 32/34 [94%] "very satisfied," p = 0.239). Conclusions: Aromatherapy treatment is not indicated intraoperatively to reduce anxiety or the use of antiemetics in patients requiring Port catheter placement. Trial registration: Clinicaltrials.gov, identifier: NCT05328973.
Introdução: Os óleos essenciais são recursos terapêuticos amplamente utilizados na aromaterapia através da inalação, uso tópico ou uso interno e reconhecida como Prática Integrativa e Complementar. Consistem em moléculas aromáticas concentradas e provenientes de plantas que podem exercer efeito positivo sob a saúde emocional, física e estética. Objetivo: O objetivo do artigo foi resumir e discutir sobre os benefícios da aromaterapia nos âmbitos mental, emocional e físico (inclusive estético) e orientar sobre o uso seguro, precauções e efeitos adversos dessa terapia alternativa. Materiais e métodos: Realizou-se revisão da literatura através de busca nas bases de dados Pubmed e Scielo utilizando os termos de busca “aromatherapy AND essential oils AND health”. Resultados: Os óleos exercem efeitos benéficos a nível emocional como ansiolítico e relaxante (óleo de lavanda ou os cítricos laranja doce, capim limão, por exemplo), bem como efeitos estimulantes, como no caso dos óleos de alecrim e hortelã-pimenta. Também são bons auxiliares em afecções respiratórias e alérgicas como rinite, sinusite e efeito analgésico em cefaleias e dores de cabeça, contusões. Além disso, são eficientes na saúde estética na prevenção de estrias, celulites, manchas de pele, auxiliar em drenagem linfática, suavização de linhas de expressão, melasmas e acne. Conclusão: Embora os benefícios sejam notáveis, o uso de óleos essenciais exige cautela quanto a sua concentração/diluição, aplicação na pele ou inalação, pois seu uso inadequado pode causar efeitos adversos como fotossensibilização, alergias, coceira, vermelhidão e até mesmo feridas.
Spray drying is a process that involves instantaneous conversion of a liquid or slurry into a free‐flowing powder in the presence of hot air or nitrogen gas current in a drying chamber. The technique is usually used to encapsulate active molecules like essential oils, plant extracts, fragrances, flavours and enzymes within a wall material. The encapsulation provides chemical and physical stability to the actives by converting them into free‐flowing powders which prevents their susceptibility to external atmospheric conditions like temperature, humidity, UV exposure and chemical oxidation. Spray drying encapsulation has an edge over other encapsulation techniques because it is fast, simple, efficient and economically feasible. The article focuses on encapsulating various essential oils within natural polymers and emulsifiers by spray drying methods to form stable microcapsules. The review also provides information on different types of spray drying equipment and process parameters like the type of atomiszer and nozzles, inlet–outlet temperature and type of cyclones. All the process parameters and materials are found to influence the physicochemical properties of the microencapsulates of essential oils. The review also discusses the effects of process parameters and materials on the encapsulation efficiency, moisture content, bulk and tapped density, agglomeration properties and thermal stability of the microencapsulates. Thus, the consolidated review will provide an overview of various optimization parameters and governing factors for obtaining microencapsulates of essential oils.
Резюме. Сучасна ароматерапія - це профілактичний, оздоровчий, повністю природний спосіб, який ефективно застосовується в практиці фізичної реабілітації. Мета – поінформувати практиків і споживачів про правила роботи з ефірними оліями та можливі побічні ефекти за допомогою сучасних гаджетів. Матеріали і методи. В роботі використані методи дослідження: проблемно-хронологічний – встановити хронологію наукового вивчення використання аромотерапії; соціологічний – дослідження медико-соціальних якостей поширення патологічних змін у вегетативній нервовій системі; аналітичний – для визначення наукових орієнтирів, застосування доказової медицини в процедурах ароматерапії; метод термінологічного аналізу, який дав змогу забезпечити розкриття сутності досліджуваних явищ; метод наукової екстраполяції, що дав змогу визначити можливості створення та застосування ароматерапії як оптимального синтезу теоретичних і практичних знань; методи багатофакторного статистичного аналізу та прогнозування для обробки даних. Завдання проекту: 1. Розробити класифікацію ефірних олій з урахуванням стандартизації вимог до них. 2. Вивчити дані про вплив аерозольної терапії натуральними ефірними оліями на мікробний та вірусний фон організму. 3. Проаналізувати зміни клітинного та гуморального імунітету до та після аерозольної терапії натуральними ефірними маслами. 4. Розробити методику та алгоритм проведення аерозольної терапії натуральними ефірними оліями, створити базу даних для ефірної олії. 5. Вивчити клінічну ефективність аерозольної терапії натуральними ефірними маслами в комплексній реабілітації. Результати. Розроблена база даних дозволить легко зорієнтуватися у величезній різноманітності запропонованих видів ефірних олій і дозволить встановити їх відповідність заводу-виробнику, що, на жаль, не завжди спостерігається в пропонованих ефірних маслах. Крім того, ароматичні масла, що входять до складу бази, повинні бути перевірені на токсичність і правильність використання. Зловживання може призвести до побічних ефектів, включаючи алергічні реакції, наркотичні, канцерогенні або нейротоксичні ефекти. Ця база даних створена з можливістю постійного оновлення та додавання нової інформації у всіх її формах, є початковим етапом створення більш повної версії та може бути затребувана зацікавленими організаціями та окремими особами через Інтернет. Висновок. Запропонована база даних дозволить легко орієнтуватися у величезній різноманітності пропонованих типів ефірних масел і дасть можливість користувачам встановлювати його відповідність із заводом-виробником, що не завжди можливо спостерігати в пропонованих до продажу ефірних оліях.
Although the introduction of glycerosomes has enriched strategies for efficient transdermal drug delivery, the inclusion of cholesterol as a membrane stabilizer has limited their clinical application. The current study describes the development and optimization of a new type of glycerosome (S-glycerosome) that is formed in glycerol solution with β-sitosterol as the stabilizer. Moreover, the transdermal permeation properties of lappaconitine (LA)-loaded S-glycerosomes and peppermint oil (PO)-mediated S-glycerosomes (PO-S-glycerosomes) are evaluated, and the lipid alterations in the stratum corneum are analyzed via lipidomics. The LA-loaded S-glycerosomes prepared by the preferred formulation from the uniform design have a mean size of 145.3 ± 7.81 nm and an encapsulation efficiency of 73.14 ± 0.35%. Moreover, the addition of PO positively impacts transdermal flux, peaking at 0.4% (w/v) PO. Tracing of the fluorescent probe P4 further revealed that PO-S-glycerosomes penetrate deeper into the skin than S-glycerosomes and conventional liposomes. Additionally, treatment with PO-S-glycerosomes alters the isoform type, number, and composition of sphingolipids, glycerophospholipids, glycerolipids, and fatty acids in the stratum corneum, with the most notable effect observed for ceramides, the main component of sphingolipids. Furthermore, the transdermal administration of LA-loaded PO-S-glycerosomes improved the treatment efficacy of xylene-induced inflammation in mice without skin irritation. Collectively, these findings demonstrate the feasibility of β-sitosterol as a stabilizer in glycerosomes. Additionally, the inclusion of PO improves the transdermal permeation of S-glycerosomes, potentially by altering the stratum corneum lipids.Graphical Abstract
Aromatic plants are utilised as traditional medicines in many cultures, but they are also traded as goods that satisfy the needs of frequently far-off marketplaces. The term “medicinal and aromatic plant” (MAP) is used in this study to refer to the entire range of plants utilised not only for medicinal purposes but also in the closely related and frequently converging fields of condiments, food, and cosmetic. Essential oil-based products are growing in popularity in various industries such as pharmaceuticals, cosmetics, food and beverage, colorants, and biopesticides and are slowly marking the realm of nanotechnology for the betterment of mankind. Due to their natural, eco-friendly, and generally accepted safety as products, these plants and the derivatives they produce are currently in higher demand. As a result, extracts from aromatic plants have the potential to develop into novel types of foods and medicines for both human and animal nutrition and health. The usage of new ideas like nutraceuticals, cosmeceuticals, phytotherapy, and aromatherapy is expanding, and there are new developments in functional foods, animal husbandry, and agricultural pest management. Aside from their possible advantages for human health, fragrant plants are also esteemed for their ecological and advantage by being an eco-friendly phytostabilizer and thus removing the heavy metal toxicity from soils. Aromatic plants are truly human assets that add value to our daily lives.
In this paper, grey correlation analysis was applied for the first time to explore the compound ratios and contribution between active constituents in the antibacterial, antioxidant, and antitumor bioactivities of rosemary-magnolia compound essential oils (EOs). The results showed that the constituents with the maximal correlation of inhibitory effects on S. aureus, E. coli, B. subtilis, B. cereus and Salmonella were as follows: Terpinolene, Eucalyptol, α-Pinene, Terpinolene and α- Phellandrene. For the ABTS and DPPH scavenging effects, the constituents with the maximal correlation were (-)-Camphor and β-Pinene, respectively. In terms of the effects of the active constituents of compound EOs on the inhibitory activities of tumor cells Mcf-7 and SGC-7901, the correlation degree ranking was the same in both tumor cells, where the three active constituents of γ- Terpinene, (R)- (+)- β- Citronellol and (-)-Camphor were in the top three. Our study determined the contribution degree of, and also provided new insights for the research of EO combination formulations.
The essential oils of Ligusticum chuanxiong Hort. (CXEO) are considered to be important parts of the pharmacological action of Ligusticum chuanxiong Hort. CXEO have a wide range of applications in various fields. Despite the interesting properties of CXEO, the volatility and low solubility have limited the application. Liposomes are vesicles composed of concentric bilayer lipids arranged around the water environment. Therefore, this study aimed to prepare stable CXEO liposomes (CXEO-LP) to improve the properties. Then, CXEO-LP were prepared by thin film dispersion method and optimized. The results showed that CXEO-LP were well dispersed. Subsequently, in vitro release and antioxidant properties of CXEO-LP were researched. CXEO-LP had slow release effect and oxidation resistance, indicating CXEO-LP may be a potential drug for treating cerebral ischemia-reperfusion injury (CIRI). The nasal mucosa toxicity test and acute toxicity test showed that CXEO-LP had no obvious toxicity to nasal cavity, heart, liver, spleen, lung and kidney tissues. Pharmacodynamic studies found that CXEO-LP significantly improved neurological deficits and brain pathology in a mouse model of CIRI compared to CXEO after intranasal administration. In general, this study showed that CXEO-LP were easy to prepare and continuously released, and had an important development prospect in the treatment of CIRI.
Special Issue of Antioxidants MDPI
In the present study, preliminary phytochemical investigations were performed on the fruit essential oil and antioxidant-rich methanolic extracts of the fruits and roots of Ferula drudeana, the putative Anatolian ecotype of the Silphion plant, to corroborate its medicinal plant potential and identify its unique characteristics amongst other Ferula species. The essential oil from the fruits of the endemic species Ferula drudeana collected from Aksaray was analyzed by GC and GC/MS. The main components of the oil were determined as shyobunone (44.2%) and 6-epishyobunone (12.6%). The essential oil of the fruits and various solvent extracts of the fruits and roots of F. drudeana were evaluated for their antibacterial and anticandidal activity using microbroth dilution methods. The essential oil of the fruits, methanol, and methylene chloride extracts of the fruits and roots showed weak to moderate inhibitory activity against all tested microorganisms with MIC values of 78–2000 µg/mL. However, the petroleum ether extract of the roots showed remarkable inhibitory activity against Candida krusei and Candida utilis with MIC values of 19.5 and 9.75 µg/mL, respectively. Furthermore, all the samples were tested for their antioxidant activities using DPPH• TLC spot testing, online HPLC–ABTS screening, and DPPH/ABTS radical scavenging activity assessment assays. Methanolic extracts of the fruits and roots showed strong antioxidant activity in both systems.
Qualitative and semi-quantitative analysis of organosulfides extracted from oil obtained by steam distillation of yellow onions was performed by gas chromatography-mass spectrometry (GC-MS). The extraction efficiency of organosulfides from onion oil was evaluated across four solvents: dichloromethane; diethyl ether; n-pentane; and hexanes. Analysis of solvent extracted organosulfides by GC-MS provided qualitative results that support the use of dichloromethane over other solvents based on identification of 27 organosulfides from the dichloromethane extract as compared to 10 from diethyl ether; 19 from n-pentane; and 17 from hexanes. Semi-quantitative evaluation of organosulfides present in the dichloromethane extract was performed using diallyl disulfide as the internal reference standard. Three organosulfides were detected in the extract at ≥5 mg/kg; 18 organosulfides between 3–5 mg/kg; and six organosulfides at <3 mg/kg. The E/Z isomers of 1-propenyl propyl trisulfide were among the most prevalent components extracted from the onion oil across all solvents; and 3,6-diethyl-1,2,4,5-tetrathiane was among the most abundant organosulfides in all solvents except hexanes. The method described here for the extraction of organosulfides from steam distilled onion oil surveys common solvents to arrive at a qualitative and semi-quantitative method of analysis for agricultural products involving onions; onion oil; and secondary metabolites of Allium spp.
Tea tree oil (TTO) and its two characteristic components (terpinen-4-ol and 1,8-cineole) have been shown to inhibit Botrytis cinerea growth. In this study, we conducted a transcriptome analysis to determine the effects of TTO and its characteristic components, alone and in combination, against B. cinerea. Most differentially expressed genes (DEGs) from B. cinerea cells treated with terpinen-4-ol participated in the biosynthesis of secondary metabolites, and the metabolism of amino acids, carbohydrates, and lipids. All treatments containing terpinen-4-ol potentially induced mitochondrial dysfunction and oxidative stress. These were further confirmed by the decreased activities of several enzymes (e.g., succinate dehydrogenase (SDH), malate dehydrogenase (MDH), α-ketoglutarate dehydrogenase (α-KGDH), isocitrate dehydrogenase (ICDH)), the increased activities of certain enzymes (e.g., catalase (CAT), peroxidase (POD), superoxide dismutase (SOD)), and increased content of hydrogen peroxide (H2O2). 1,8-Cineole mainly affected DEGs involved in genetic information processing, resulting in cell death. This study provides insight into the molecular mechanism of B. cinerea inhibition by TTO, and explains the synergistic effect of terpinen-4-ol and 1,8-cineole on B. cinerea.
Background:
According to our previous study, microglia P2X4 receptors (P2X4Rs) play a pivotal role in the central sensitization of chronic migraine (CM). However, the molecular mechanism that underlies the crosstalk between microglia P2X4Rs and neurons of the trigeminal nucleus caudalis (TNC) is not fully understood. Therefore, the aim of this study is to examine the exact P2X4Rs signalling pathway in the development of central sensitization in a CM animal model.
Methods:
We used an animal model with recurrent intermittent administration of nitroglycerin (NTG), which closely mimics CM. NTG-induced basal mechanical and thermal hypersensitivity were evaluated using a von Frey filament test and an increasing-temperature hot plate apparatus (IITC). We detected P2X4Rs, brain-derived neurotrophic factor (BDNF) and phosphorylated p38 mitogen-activated protein kinase (p-p38-MAPK) expression profiles in the TNC. We investigated the effects of a P2X4R inhibitor (5-BDBD) and an agonist (IVM) on NTG-induced hyperalgesia and neurochemical changes as well as on the expression of p-p38-MAPK and BDNF. We also detected the effects of a tropomyosin-related kinase B (TrkB) inhibitor (ANA-12) on the CM animal model in vivo. Then, we evaluated the effect of 5-BDBD and SB203580 (a p38-MAPK inhibitors) on the release and synthesis of BDNF in BV2 microglia cells treated with 50 μM adenosine triphosphate (ATP).
Results:
Chronic intermittent administration of NTG resulted in chronic mechanical and thermal hyperalgesia, accompanied by the upregulation of P2X4Rs and BDNF expression. 5-BDBD or ANA-12 prevented hyperalgesia induced by NTG, which was associated with a significant inhibition of the NTG-induced increase in phosphorylated extracellular regulated protein kinases (p-ERK) and calcitonin gene related peptide (CGRP) release in the TNC. Repeated administration of IVM produced sustained hyperalgesia and significantly increased the levels of p-ERK and CGRP release in the TNC. Activating P2X4Rs with ATP triggered BDNF release and increased BDNF synthesis in BV2 microglia, and these results were then reduced by 5-BDBD or SB203580.
Conclusions:
Our results indicated that the P2X4R contributes to the central sensitization of CM by releasing BDNF and promoting TNC neuronal hyper-excitability. Blocking microglia P2X4R-BDNF signalling may have an effect on the prevention of migraine chronification.
Background:
Prevalence of migraine, as a chronic neurovascular disorder, was approximately 10.3 and 23.1% among men and women, respectively, mostly in people younger than 40 years old. Migraine is prevalent in different geographic areas worldwide. The present study was designed to compare the impact of intranasal lidocaine 4% and peppermint essential oil drop 1.5% on migraine attacks.
Methods:
In this double-blind, parallel, randomized controlled trial, 120 adult patients with a diagnosis of migraine based on the International Headache Society criteria were treated with intranasal lidocaine drop 4% or peppermint essential oil drop 1.5% or placebo. Patients expressed their symptoms 5 and 15 min after dripping, and if they still had a headache after 15 min, they were given the second dose. Patients with a second dose of medication, 15 min later recorded their headache rate. All patients recorded their symptoms after 30 min. Symptoms of the patients were followed by a researcher through the phone and in-person after 2 months. Then, the questionnaires were filled.
Results:
In the present study, there was a significant difference among groups in headache intensity after treatment (P < 0.001). In 40% of the patients in the peppermint oil and lidocaine groups, the intensity of headache decreased. In the placebo group, fewer patients responded highly to the treatment, whereas 41.5% of patients in the lidocaine group and 42.1% of patients in the peppermint oil group responded to the treatment considerably.
Conclusions:
Concerning the findings of the present study, nasal application of peppermint oil caused considerable reduction in the intensity and frequency of headache and relieved majority of patients' pain similar to lidocaine. On the basis of findings of this study, it can be concluded that nasal menthol, such as lidocaine, can be used to relieve migraine headaches.
Introduction: Migraine is the most common of all neurological disorders. A breakthrough in migraine treatment emerged in the early nineties with the introduction of 5-HT1B/D receptor agonists called triptans. Triptans are used as the standard of care for acute migraine; however, they have significant limitations such as incomplete and inconsistent pain relief, high rates of headache recurrence, class- specific side effects and cardiovascular contraindications. First- and second-generation calcitonin gene-related peptide (CGRP) receptor antagonists, namely gepants, is a class of drugs primarily developed for the acute treatment of migraine. CGRP is the most evaluated target for migraine treatments that are in development.
Areas covered: This article reviews the available data for first- and second-generation CGRP receptor antagonists, the role of CGRPs in human physiology and migraine pathophysiology and the possible mechanism of action and safety of CGRP targeted drugs.
Expert opinion: Available data suggest that second generation of gepants has clinical efficacy similar to triptans and lasmiditan (5-HT1F receptor agonist) and has improved tolerability. Future studies will assess their safety, especially in specific populations such as patients with cardiovascular disease and pregnant women.
Background
Central sensitization is an important mechanism of chronic migraine (CM) and is related to the inflammatory response of microglia. The NOD-like receptor protein 3 (NLRP3) inflammasome may regulate the inflammatory process of microglia in several neurological diseases, but its role in CM is largely unknown. Therefore, the aim of this study was to identify the precise role of microglial NLRP3 in CM.
Methods
An experimental CM mouse model was established by repeated intraperitoneal (i.p) injection with nitroglycerin (NTG). We evaluated the expression levels of NLRP3 and its downstream interleukin (IL)-1β protein in the trigeminal nucleus caudalis (TNC; which is a central area relevant to migraine pain) at different time points. To further examine the effects of the NLRP3 inflammasome pathway on central sensitization of CM, we examined MCC950, an NLRP3 inflammasome-specific inhibitor, and IL-1ra, an IL-1β antagonist, whether altered NTG-induced mechanical hyperalgesia of the periorbital area and hind paw. The effect of MCC950 and IL-1ra on c-Fos, phosphorylated extracellular signal-regulated kinase (p-ERK) and calcitonin gene-related peptide (CGRP) expression in the TNC were also analyzed. The cell localization of NLRP3 and IL-1β in the TNC was evaluated by immunofluorescence staining.
Results
Repeated NTG administration induced acute and chronic mechanical hyperalgesia and increased expression of NLRP3 and IL-1β. Blockade of NLRP3 or IL-1β reduced NTG-induced hyperalgesia, and this effect was accompanied by a significant inhibition of the NTG-induced increase in p-ERK, c-Fos and CGRP levels in the TNC. Immunofluorescence staining revealed that NLRP3 and IL-1β were mainly expressed in microglia in the TNC, and the IL-1β receptor, IL-1R, was mainly expressed in neurons in the TNC.
Conclusions
These results indicate that NLRP3 activation in the TNC participates in the microglial-neuronal signal by mediating the inflammatory response. This process contributes to the central sensitization observed in CM.
Electronic supplementary material
The online version of this article (10.1186/s12974-019-1459-7) contains supplementary material, which is available to authorized users.
Neuropathic pain (NP) is associated with chronic hyperglycemia and emotional disorders such as depression in diabetic patients, complicating the course of treatment. Drugs currently used to treat NP have undesirable side effects, so research on other natural sources has been required. β-caryophyllene (BCP), a natural sesquiterpene found in some food condiments and considered an agonist to cannabinoid receptor type 2, could have potential therapeutic effects to treat conditions such as NP and emotional disorders. For this reason, we assessed whether BCP modulates nociception, anxiety, and depressive-like behavior in streptozotocin (STZ)-induced experimental diabetic BALB/c female mice. BCP was orally chronic administrated (10 mg/kg/60 μL). Pain developed with STZ was evaluated with von Frey filament test, SMALGO®, and hot plate test. Anxiety and depression-like behavior were assessed by marbles test, forced swim test, and tail suspension test. BCP significantly reduced glycemia in experimental diabetic mice. The pain was also mitigated by BCP administration. Depression-like behavior assessed with tail suspension test was attenuated with orally chronic BCP administration. Substance P and cytokines such as interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α), and interleukin-6 (IL-6) were also attenuated with BCP administration. NP was positively correlated with substance P and IL-6 and IL-1β release. Our data using an orally chronic BCP administration in the STZ challenged mice to suggest that glycemia, diabetes-related NP, and depressive-like behavior could be prevented/reduced by dietary BCP.
Transient receptor potential ankyrin 1 (TRPA1) is a key player in pain and neurogenic inflammation, and is localized in nociceptive primary sensory dorsal root ganglion (DRG) neurons. TRPA1 plays a major role in the transmission of nociceptive sensory signals. The generation of neurogenic inflammation appears to involve TRPA1-evoked release of calcitonin gene-related peptide (CGRP). However, it remains unknown whether TRPA1 or CGRP expression is affected by TRPA1 activation. Thus, in this study, we examined TRPA1 and CGRP expression in DRG neurons in vitro after treatment with the TRPA1 activator formaldehyde or the TRPA1 blocker menthol. In addition, we examined the role of extracellular signal-regulated protein kinase 1/2 (ERK1/2) in this process. DRG neurons in culture were exposed to formaldehyde, menthol, the ERK1/2 inhibitor PD98059 + formaldehyde, or PD98059 + menthol. After treatment, real-time polymerase chain reaction, western blot assay and double immunofluorescence labeling were performed to evaluate TRPA1 and CGRP expression in DRG neurons. Formaldehyde elevated mRNA and protein levels of TRPA1 and CGRP, as well as the proportion of TRPA1- and CGRP-positive neurons. In contrast, menthol reduced TRPA1 and CGRP expression. Furthermore, the effects of formaldehyde, but not menthol, on CGRP expression were blocked by pretreatment with PD98059. PD98059 pretreatment did not affect TRPA1 expression in the presence of formaldehyde or menthol.
Neuropathic pain is an intractable disease with few definitive therapeutic options. Anethole (AN) has been confirmed to possess potent anti-inflammatory and neuroprotective properties, but its effect on neuropathic pain has not been reported. The present study was designed to investigate the antinociceptive effect of AN on chronic constriction injury (CCI)-induced neuropathic pain in mice. AN (125, 250, and 500 mg/kg) and pregabalin (40 mg/kg) were intragastric administered for 8 consecutive days from the 7th day post-surgery. Behavioral parameters were measured on different days, namely, 0, 7, 8, 10, 12, and 14, from CCI operation. Additionally, electrophysiological and histopathological changes were analyzed on the 14th day. Afterward, immunofluorescence and Western blot were utilized to examine the activation of glial cells and the expression of inflammatory cytokines, respectively. AN treatment of CCI mice considerably alleviated hyperalgesia and allodynia, ameliorated abnormal sciatic nerve conduction, and restored injured sciatic nerves in a dose-dependent manner. Furthermore, AN suppressed the activation of glial cells, down-regulated pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-α), interleukin (IL-6, and IL-1β), and up-regulated the anti-inflammatory cytokine (IL-10). These assays first indicated that AN exerted an antinociceptive effect on CCI-induced neuropathic pain, and might be attributed to the anti-inflammatory and neuroprotective activities of AN.
Background:
Diallyl trisulfide (DATS), a garlic-derived organosulfuric compound, has been documented for potential anti-inflammatory effects. However, the mechanism in microglia remains unknown. In this study, we investigated the anti-inflammatory effects of DATS in lipopolysaccharide (LPS)-stimulated BV2 microglial cells.
Methods:
The effects of DATS on LPS-induced pro-inflammatory mediators such as nitric oxide (NO) and prostaglandin E2 (PGE2) were assessed under conditions not in the cytotoxicity of DATS. The protein expression of inflammation regulatory genes was measured by Western blot analysis.
Results:
DATS significantly inhibited the LPS-induced secretion of NO and PGE2, which was associated with the suppression of their regulatory genes, inducible NO synthase and COX-2. DATS had been shown to inhibit nuclear translocation of NF-κB by destroying the degradation and phosphorylation of IκB-α inhibitors in the cytoplasm. In addition, DATS effectively inhibited the expression of LPS-induced toll-like receptor 4 (TLR4) and myeloid differentiation factor 88. Furthermore, DATS markedly reduced the LPS-induced expression of chemokine (CXC motif) ligand (CXCL) 12 and CXC receptor (CXCR) 4, demonstrating its capacity to block chemo-attractive activity.
Conclusions:
These results indicate that DATS inhibits the activation of the CXCL12/CXCR4 axis associated with antagonizing effect on TLR4 and blocks NF-κB signaling, thus demonstrating anti-inflammatory effects against LPS stimulation.
Background/aims:
Spinal cord injury (SCI) is a serious global problem that leads to permanent motor and sensory deficits. This study explores the anti-apoptotic and neuroprotective effects of the natural extract β-elemene in vitro and in a rat model of SCI.
Methods:
CCK-8 assay was used to evaluate cell viability and lactate dehydrogenase assay was used to evaluate cytotoxicity. A model of cell injury was established using cobalt chloride. Apoptosis was evaluated using a fluorescence-activated cell sorting assay of annexin V-FITC and propidium iodide staining. A rat SCI model was created via the modified Allen's method and Basso, Beattie, and Bresnahan (BBB) scores were used to assess locomotor function. Inflammatory responses were assessed via enzyme-linked immunosorbent assay (ELISA). Apoptotic and surviving neurons in the ventral horn were respectively observed via terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and Nissl staining. Western blotting was used to measure protein expression.
Results:
β-elemene (20 μg/ml) promoted cell viability by activating phosphorylation of the PI3K-AKT-mTOR pathway. β-elemene reduced CoCl2-induced cellular death and apoptosis by suppressing the expression levels of CHOP, cleaved-caspase 12, 78-kilodalton glucose-regulated protein, cleaved-caspase 3, and the Bax/Bcl-2 ratio. In the rat model of SCI, Nissl and TUNEL staining showed that β-elemene promoted motor neuron survival and reduced neuronal apoptosis in the spinal cord ventral horn. BBB scores showed that β-elemene significantly promoted locomotor behavioral recovery after SCI. In addition, β-elemene reduced the ELISA-detected secretion of interleukin (IL)-6 and IL-1β.
Conclusion:
β-elemene reduces neuronal apoptosis by alleviating endoplasmic reticulum stress in vitro and in vivo. In addition, β-elemene promotes locomotor function recovery and tissue repair in SCI rats. Thus, our study provides a novel encouraging strategy for the potential treatment of β-elemene in SCI patients.
The current study investigated the action of β‐caryophyllene, the major constituent of copaiba oil, on the systemic inflammation, oxidative status, and liver cell metabolism of rats with adjuvant‐induced arthritis, a model for rheumatoid arthritis. This study also compared the actions of β‐caryophyllene with those previously reported for copaiba oil on arthritic rats. For this purpose, Holtzman healthy and arthritic rats received 215 and 430 mg·kg⁻¹ β‐caryophyllene orally once a day during 18 days. Both doses of β‐caryophyllene reduced the adjuvant‐induced paw edema, swollen of lymph nodes, and number of circulating and articular leukocytes. β‐Caryophyllene, at the dose of 430 mg·kg ⁻¹, abolished the increases of protein carbonyl groups and myeloperoxidase activity in the liver and plasma of arthritic rats and, at both doses, it restored the increased levels of reactive oxygen species and reduced glutathione in the arthritic liver. These beneficial actions were of the same extension as those of copaiba oil ( Copaifera reticulata) and, therefore, β‐caryophyllene is possibly responsible for the anti‐inflammatory and antioxidant actions of the oil. Hepatic gluconeogenesis was 40% lower in arthritic rats, which also presented a reduced number of hepatocytes per liver area (−23%) associated with increased hepatocyte area (+18%) and liver weight (+50%). None of these hepatic alterations were improved by β‐caryophyllene, but not even by ibuprofen. However, unlike copaiba oil, β‐caryophyllene did not modify the hepatic morphology and metabolism of healthy rats. These results reveal that β‐caryophyllene improves the systemic inflammation and oxidative status of arthritic rats and, in addition, it was not associated with hepatotoxicity.
Background:
Cinnamomum camphora has been cultivated as an economically important tree for its medicinal and aromatic properties. Selective breeding has produced Cinnamomum plants for special uses, including spice strains with characteristic flavors and aromas and high-potency medicinal cultivars. The molecular biology underlying terpenoid biosynthesis is still unexplored.
Results:
Gas chromatography-mass spectrometry was used to analyze the differences in contents and compositions of essential oil terpenoids in linalool- and borneol-type chemotypes of C. camphora. The data revealed that the essential oils consist primarily of monoterpenes with only very minor quantities of sesquiterpenes and diterpenes and that the essential oil differs in different chemotypes of C. camphora, with higher yields of (-)-borneol from the borneol-type than from the linalool-type. To study the terpenoid biosynthesis of signature compounds of the major monoterpenes, we performed RNA sequencing to profile the leaf transcriptomes of the two chemotypes of C. camphora. A total of 23.76 Gb clean data was generated from two chemotypes and assembled into 156,184 unigenes. The total length, average length, N50 and GC content of unigenes were 155,645,929 bp, 997 bp, 1430 bp, and 46.5%, respectively. Among them, 76,421 unigenes were annotated by publicly available databases, of which 67 candidate unigenes were identified to be involved in terpenoid biosynthesis in C. camphora. A total of 2863 unigenes were identified to be differentially expression between borneol-type and linalool-type, including 1714 up-regulated and 1149 down-regulated unigenes. Most genes encoding proteins involved in terpenoid precursor MVA and MEP pathways were expressed in similar levels in both chemotypes of C. camphora. In addition, 10 and 17 DEGs were significantly enriched in the terpene synthase activity and oxidoreductase activity terms of their directed acyclic graphs (DAG), respectively. Three monoterpene synthase genes, TPS14-like1, TPS14-like2 and TPS14-like3 were up-regulated in the borneol-type compared to the linalool-type, and their expression levels were further verified using quantitative real-time PCR.
Conclusions:
This study provides a global overview of gene expression patterns related to terpenoid biosynthesis in C. camphora, and could contribute to a better understanding of the differential accumulation of terpenoids in different C. camphora chemotypes.
The present study used isometric tension recording to investigate the vasorelaxant effect of limonene (LM), carveol (CV), and perillyl alcohol (POH) on contractility parameters of the rat aorta, focusing in particular on the structure-activity relationship. LM, CV, and POH showed a reversible inhibitory effect on the contraction induced by electromechanical and pharmacomechanical coupling. In the case of LM, but not CV and POH, this effect was influenced by preservation of the endothelium. POH and CV but not LM exhibited greater pharmacological potency on BayK-8644-induced contraction and on electromechanical coupling than on pharmacomechanical coupling. In endothelium-denuded preparations, the order of pharmacological potency on electrochemical coupling was LM < CV < POH. These compounds inhibited also, with grossly similar pharmacological potency, the contraction induced by phorbol ester dibutyrate. The present results suggest that LM, CV and POH induced relaxant effect on vascular smooth muscle by means of different mechanisms likely to include inhibition of PKC and IP3 pathway. For CV and POH, hydroxylated compounds, it was in electromechanical coupling that the greater pharmacological potency was observed, thus suggesting a relative specificity for a mechanism likely to be important in electromechanical coupling, for example, blockade of voltage-dependent calcium channel.
Purpose of review:
Vasoactive peptides play a key role in the attack-initiating cascade of migraine. Recent studies have highlighted a potentially important role for endothelin-1, a potent vasoconstrictor peptide, in migraine pathophysiology. Here, we review the current data on endothelin's involvement in migraine.
Recent findings:
We identified 23 articles. Nine studies reported on endothelin-1 plasma concentrations in patients with migraine, eight studies investigated relevant genetic associations, five studies investigated endothelin-1 and spreading depression in animals, and one randomized controlled clinical trial tested the efficacy of an endothelin antagonist in the acute treatment of migraine in patients both with and without aura. Elevated endothelin-1 plasma levels have been reported in the early phase of migraine attacks. Genetic abnormalities related to the endothelin type A receptor have been reported in migraineurs. Endothelin-1 potently induces spreading depression in animals, which may explain the connection between endothelial irritation and migraine aura. Endothelin-1 could be a primary factor in the attack-triggering cascade of migraine attacks with and without aura. Additional studies in humans and animal models are needed to further elucidate the role of endothelin-1 in migraine.
The Treatment Guideline Subcommittee of the Taiwan Headache Society evaluated the medications currently used for migraine prevention in Taiwan. We assessed the results of new published drug trials, information from medical database and referred to the latest guidelines published. After comprehensive discussion, we proposed Taiwanese consensus about the preventive treatment for migraine including recommendation levels, strength of evidences, and related prescription information regarding dosage and adverse effects. This guideline is updated from earlier version published in 2008. Migraine preventive medications currently available in Taiwan can be categorized into ß-blockers, antidepressants, calcium channel blockers, anticonvulsants, nonsteroid anti-inflammatory drugs, OnabotulinumtoxinA and miscellaneous medications. Propranolol has the best level of evidence and fewer side-effects, and is recommended as the first-line medication for episodic migraine prevention. Valproic acid, topiramate, flunarizine and amitriptyline are suggested as the second-line medications. The rest medications are used when the above medications fail. OnabotulinumtoxinA and topiramate are recommended for chronic migraine prevention. Those other medications used for episodic migraine could also be used as a second-line option. It is not recommended to use migraine preventive medication during pregnancy or lactation. For those women with menstrual migraine, nonsteroid anti-inflammatory drugs and triptans can be used for prevention during the menstrual period. The levels of evidences for migraine preventive medications in children/adolescents and elderly are low. The preventive medications should follow the “start low and go slow” doctrine to reach an effective dosage. This can prevent adverse events and improve tolerance. The efficacy of preventive medications cannot be evaluated until 3 to 4 weeks after treatment. If the improvement of migraine maintains for 6 months, physicians can gradually taper the medications. Physicians should notify the patients not to overuse acute medications during migraine prevention treatment. © 2017, Neurological Society R.O.C (Taiwan). All rights reserved.
Background
Hypercholesterolemia is a major risk factor for development of atherosclerosis. The present study was conducted to evaluate the potential effect of ginger oil alone or combined with rosemary oil as hypocholesterolemic agent in rats fed high fat diet.
Materials and methods
Healthy female albino rats (n=80) weighting about (150-180 g) were included in this study divided into two equal groups; Group (I): were fed on the basal diet. Group (I) were divided into 4 subgroups each 10: Group (Ia): negative control. Group (Ib): Rats received i.p 2.5 g/Kg b.w of ginger oil. Group (Ic): rats received i.p 2.5 g/Kg b.w of rosemary oil. Group (Id): Rats received i.p 5 g/Kg b.w mixture of ginger oil and rosemary oil (1:1). The second main groups; Group (II): high fat diet (HFD) were fed on the basal diet plus cholesterol (1%), bile salt (0.25%) and animal fat (15%) to induce hypercholesterolemia for six weeks. Group (II) was divided into 4subgroups: Group (IIa): HFD. Group (IIb): HFD were treated with i.p 2.5 g/Kg b.w ginger oil. Group (IIc): (n=10) HFD were treated with i.p 2.5 g/Kg b.w rosemary oil. Group (IId): (n=10) HFD were treated with i.p 5 g/Kg b.w mixture of oils.
Results
It was found that HFD rats showed a significant elevation in glucose, total cholesterol, triglyceride, GOT, GPT, alkaline phosphatase and a reduction in serum HDL-c compared with negative control. Treatment with ginger oil, rosemary oil and their mixture modulated the elevation of these parameters. Histopathological examination of the liver tissue of HFD rats showed a lipid deposition and macrophage infiltration and stenosis of hepatic vein. Treatment with mixture oils preserves normal structure of liver.
Conclusion
It was concluded that, hypocholesterolemic effect was related to the active oil content as Rosemary oil contain - α-pinene, Camphor, cineole, borneol and Ginger oil contain Linalool, Terpineol, Borneol, Eucalyptol.
Magnoliae Flos is a commonly used traditional medicinal material in Asia. It is used to treat sinusitis, nasal congestion, and hypersensitive skin. Because Magonlia Flos was described as an aromatic material in ancient Chinese texts, we hypothesized that its essential oil may be used to treat immune disorders. Dendritic cells (DCs), regarded as a major target of immunomodulators to control immune responses, play a critical role in the adaptive immune response. In this study, Magnoliae Flos essential oil (MFEO) decreased the production of the cytokines TNF-
α
, IL-6, and IL-12p70 in lipopolysaccharide (LPS)-stimulated DCs. It also suppressed the surface markers MHC II, CD80, and CD86 in LPS-stimulated DCs. Animal models demonstrated that the 2,4-Dinitro-1-fluorobenzene (DNFB) inducing a contact hypersensitivity response was inhibited following treatment with MFEO. In addition, MFEO inhibited the infiltration of T cells in the ears of DNFB-induced mice. To explore its bioactive compounds, the components of MFEO were analyzed using gas chromatography (GC) and GC-mass spectrometry. The results revealed that the major compounds in MFEO are camphor and 1,8-cineole. Additional DC bioassays confirmed that these compounds substantially suppressed cytokine production in LPS-induced DCs. Therefore, we demonstrated that MFEO exhibits an immunosuppressive effect both in vivo and in vitro, and camphor and 1,8-cineole may be the major components responsible for its immunosuppressive ability. The findings indicate that MFEO has the potential to be developed as a new immunosuppressant for excessive diseases.
Ethnopharmacological relevance: The objective of traditional Chinese medicine (TCM) combination theory is to "reduce toxicity and increase efficiency", especially to solve the liver toxicity of many TCMs. Fructus Meliae Toosendan (CLZ)‐Fructus Foeniculi (XHX) is a typical traditional Chinese herb pair that decreases the toxicity and increases the efficiency of the herbs. Fructus Meliae Toosendan (CLZ, cold‐natured) has significant liver toxicity. However, it has been widely used in combination with Fructus Foeniculi (XHX, hot‐natured) for thousands of years in TCM, which shows no hepatotoxicity, indicating that the combined use of XHX and CLZ can reduce the hepatotoxicity of CLZ. Herb‐herb interactions (HHIs) could affect herb pharmacokinetics and its in vivo efficacy. The HHIs between CLZ and XHX are still unknown.
Materials and methods: This study used Liquid Chromatography tandem Mass Spectrometry (LC‐MS) and Gas Chromatography tandem Mass Spectrometry (GC‐MS) to establish methods for detecting toosendanin and trans‐anethole, the main active substances of CLZ and XHX, respectively. Additionally, we investigated their herb‐herb interactions via pharmacokinetic and pharmacodynamic studies.
Results: The results indicate that the established analytical methods are suitable for detecting toosendanin and trans‐anethole, and the methodology meets the requirements of biological sample testing methods. Compared to the CLZ group, the pharmacokinetic parameters Cmax, AUC(0‐t), AUC(0‐∞), MRT(0‐t) and MRT(0‐∞) of toosendanin in the CLZ‐XHX group notably decreased, the values of Vz/F remarkably increased. Compared to the XHX group, the pharmacokinetic parameters Cmax, AUC0‐t, AUC0‐∞, Tmax and t1/2z of trans‐anethole notably increased in the CLZ‐XHX group, the values of CLz/F and Vz/F obviously decrease.
Conclusion: The pharmacokinetic results indicate that XHX can significantly decrease the absorption and bioavailability and accelerate the elimination process of toosendanin in CLZ. XHX could decrease the risk of in vivo accumulation of the toxic constituent of CLZ, toosendanin, thus decreasing its toxicity. It has also been shown that CLZ can significantly increase absorption and bioavailability and attenuate the elimination process of trans‐anethole in XHX, thus enhancing its efficacy. Hepatotoxicity studies indicate that CLZ has significant hepatotoxicity, and its combined use with XHX can decrease its liver damaging properties.
Objective:
Complementary therapies have been increasingly used for the prevention and treatment of migraine so that there is a need for studies in this setting. This study sought to determine the effects of basil essential oil on the severity and frequency of migraine attack headaches.
Methods:
A triple-blind clinical trial study was performed on 144 patients diagnosed with migraine. Patients were randomly allocated by a stratified method to four groups of 36 titled basil essential oil 2, 4, 6%, and placebo groups. Medications were used topically every 8 h for 3 successive months. In addition, each individual received 325 mg of acetaminophen every 12 h. The severity and frequency of migraine attacks were measured prior to the study, at weeks 2, 4, 8, and 12. The visual analog scale was used to measure pain intensity. The marginal model and generalized estimation equations were used to compare changes in the intensity and frequency of pain over time.
Results:
The interaction of the dose and time factors was significant on both pain intensity (p < 0.001) and frequency of attack (p < 0.001). The odds ratio of higher pain intensity and rate ratio of higher frequency of attack in the intervention groups compared to the placebo group were decreased over the study time.
Conclusion:
Time lapse and higher doses of basil essential oil would reduce both the intensity and frequency of migraine attacks.
Microglia are the innate immune cells in the nervous system. In the resting state, they display a ramified morphology, while upon disease stimulation their processes would be retracted, along with pro-inflammatory cytokine overproduction. Reversing microglial process retraction may help reduce pro-inflammatory cytokine production and restore microglia's ability to scan surrounding environments, rendering brain function regulation to be more effective. We found that diallyl disulfide (DADS), a major organosulfur compound in garlic oil, administered at different doses and time points, promoted microglial process elongation in both cultured systems and prefrontal cortexes in mice in a reversible manner. Lipopolysaccharide (LPS), a classical activator of microglia, did not affect this pro-elongation effect of DADS at conditions in vitro and in vivo. Functional studies revealed that DADS pre-treatment attenuated LPS-induced decreases in levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) mRNA as well as LPS-induced increases in levels of IL-10 and CD206 mRNA in both cultured microglia and prefrontal cortexes in mice. Protein kinase B (Akt) inhibition attenuated the pro-elongation effect of DADS on microglial process and blocked the regulatory effects of DADS on LPS-induced inflammatory responses in both cultured microglia and prefrontal cortexes in mice. In an in vivo model of neuroinflammation, DADS pre-treatment prevented LPS-induced retraction of microglial process in the prefrontal cortex in mice, and attenuated LPS-induced increase in immobility time in the tail suspension test and forced swim test. These results indicate that DADS induces an Akt-dependent elongation of microglia process, along with the induction of an anti-inflammatory phenotype.
Migraine headaches are among the most common and potentially debilitating disorders encountered by primary healthcare providers. In the treatment of acute migraine and the prevention of recurrent attacks, there are prescription drugs of proven benefit. However, for those without health insurance or high co-pays, these drugs may be neither available nor affordable and, for all patients, they may be either poorly tolerated or contraindicated.
The totality of evidence, which includes data from randomized trials, suggests that high-dose aspirin, in doses from 900 to 1300 mg, taken at the onset of symptoms, is an effective and safe treatment option for acute migraine headaches. In addition, the totality of evidence, including some, but not all, randomized trials, suggests the possibility that daily aspirin, in doses from 81 to 325 mg, may be an effective and safe treatment option for the prevention of recurrent migraine headaches.
The relatively favorable side effect profile of aspirin and extremely low costs compared with other prescription drug therapies may provide additional options for primary healthcare providers in the treatment of both acute and recurrent migraine headaches.
Objectives:
Oxidative stress and inflammation have a critical role in the pathogenesis of ischaemic stroke. Alpha-pinene is a monoterpenoid molecule with anti-inflammatory and antioxidant properties. The nobility of the present study was to evaluate the neuroprotective effect of α-pinene in ischaemic stroke.
Methods:
Ischaemic stroke was induced by transient middle cerebral artery occlusion followed by 24 h reperfusion in male Wistar rats. Alpha-pinene (25, 50 and 100 mg/kg, i.p.) was administered in the beginning of reperfusion. Then, the neurobehavioural function, infarct volume, brain oedema, antioxidant enzyme activity and the concentration of malondialdehyde (MDA), nitric oxide (NO) and interleukin-6 (IL-6) were evaluated by different methods in the brain.
Key findings:
Alpha-pinene (50 and 100 mg/kg) elicited a significant decrease in the brain oedema and infarct size as well as an improvement in the neurobehavioural function. Besides, α-pinene (100 mg/kg) restored the function of superoxide dismutase, catalase and glutathione peroxidase and reduced the concentration of MDA, NO and IL-6 in the hippocampus, cortex and striatum.
Conclusions:
It was ultimately attainted that α-pinene exerts neuroprotective effect in ischaemic stroke in rat through the restoration of antioxidant enzymes activity, attenuation of lipid peroxidation and reduction of inflammation in the ischaemic brains.
Frankincense, an oleoresin produced by Boswellia species, has historical medicinal and religious significance, and is today used extensively for its essential oil. Boswellia dalzielii, a species found in West Africa, is one of the few frankincense species for which there is no information on the oleoresin essential oil. In order to correct this deficiency, the chemical compositions of the essential oil hydrodistilled from 21 samples of oleoresin taken directly from B. dalzielii trees in northern Nigeria, were analyzed by gas chromatography – mass spectrometry as well as chiral gas chromatography. In addition, a hierarchical cluster analysis was performed on the essential oil compositions from the 21 oleoresin samples from northern Nigeria as well as two samples from Ghana. The essential oil fractions obtained by hydrodistillation of B. dalzielii oleoresins were dominated by α-pinene (21.7–76.6%), followed by α-thujene (2.0–17.6%), myrcene (up to 35.2%), p-cymene (0.3–15.6%), and limonene (1.1–32.9%). The levorotatory enantiomers predominated for the monoterpenes with 98.1 ± 1.5% (−)-α-thujene, 99.2 ± 0.5% (−)-α-pinene, and 96.8 ± 1.4% (−)-β-pinene. Limonene showed the largest variation in enantiomeric distribution [67.3 ± 12.1% (−)-limonene]. The cluster analysis revealed two major chemotypes, one dominated by α-pinene and one much rarer chemotype rich in myrcene.
The stress-induced hormone corticosterone initiates oxidative stress and inflammatory responses, culminating in cell apoptosis and neurological changes. We assessed the effects of D-Limonene on a PC12 cellular model of corticosterone-induced neurotoxicity, and whether these effects involved the AMP-activated protein kinase (AMPKα) pathway. PC12 cells were treated with corticosterone with or without D-limonene for 24 h. Western blots were performed to measure activation of AMPK pathway members [Silent mating type information regulation 2 homolog-1 (SIRT1), AMPKα, and nuclear factor (NFκB)], reactive oxygen species, inflammatory cytokines, and markers of apoptosis. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) was used to measure cell death after treatment. D-Limonene reversed the effects of corticosterone on PC12 cells: it decreased the levels of malondialdehyde (MDA) and nitric oxide (NO), activities of NADPH oxidase (p67-phox and p47-phox), expression of pro-inflammatory markers [inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin 6 (IL-6), interleukin 1β (IL-1β), and tumor necrosis factor α (TNF-α)], and expression of pro-apoptotic proteins [Bcl2 associated with X protein (Bax) and cleaved caspase-3)]. D-Limonene also increased levels of the antioxidant enzymes superoxide dismutase 1 (SOD1) and heme oxygenase 1 (HO-1) and the anti-apoptotic protein Bcl-2 while decreasing the number of TUNEL-positive cells. D-limonene significantly activated AMPKα and suppressed NF-κB nuclear translocation through up-regulation of SIRT1. Addition of compound C, an AMPK inhibitor, severely weakened these neuroprotective effects of D-limonene. D-Limonene has a neuroprotective effect on corticosterone-induced PC12 cell injury induced by activating the AMPKα signaling pathway, and thereby inhibiting reactive oxygen species and inflammatory factors. These data suggest that D-limonene might protect against neuronal death to improve depressive symptoms.
Seyed Hamdollah Mosavat has made substantial contributions in conception, designing, acquisition of data and preformed clinical trial., Amin Moayedfard and Abbas Rahimi Jaberi had contribution in designing and preformed clinical trial. Zahra Sobhani and Maryam Mosaffa-Jahromi designed and prepared drugs of study. Aida Iraji has made drug biochemical assay. Seyed Hamdollah Mosavat had contribution in designing and revised the manuscript critically for important intellectual content and had contribution in designing and analyzing of data. Seyed Hamdollah Mosavat, Amin Moayedfard and Abbas Rahimi Jaberi had contribution in conception and designing and revised the manuscript critically for important intellectual content. All authors read and approved the final manuscript.
The aim of this study was to evaluate the antibacterial activity of coriander essential oil and its major constituent, linalool, in combination with antibiotics against Gram‐positive (methicillin‐susceptible and methicillin‐resistant Staphylococcus aureus, Staph. epidermidis) and Gram‐negative bacteria (Pseudomonas aeruginosa, Escherichia coli). The chemical composition of coriander essential oil was analyzed by gas chromatography with flame ionization and mass spectrometry detection. The antibacterial activity of coriander essential oil, linalool and their combinations with antibiotics were assessed by the broth microdilution and checkerboard assays, respectively. Thirty‐four compounds were identified in coriander essential oil, linalool (70.11%) being predominant. Coriander essential oil and linalool showed synergistic interactions with antibiotics (oxacillin, amoxicillin, gentamicin, ciprofloxacin, tetracycline) against both Gram‐positive and Gram‐negative bacteria. In these synergistic combinations, minimum inhibitory concentrations of antibiotics were markedly reduced; even antibiotic resistance reversal activity was recorded. These findings are very promising for the development of new therapeutic options for bacterial infections.
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Beta-caryophyllene (BCP) is a phytocannabinoid possessing selective agonistic activity to cannabinoid type-2 receptors (CB2R) and peroxisome proliferator-activated receptors-α (PPAR-α). However, few studies reported the contribution of PPAR-γ receptors in BCP effects. The aim of this study was to investigate the BCP effects on diet-induced dyslipidemia and vascular inflammation as well as the involvement of CB2R and PPAR-γ receptors. Wistar rats were fed a high-fat diet and administered 10% fructose for 12 weeks. Treatment with pioglitazone, BCP, BCP + CB2R antagonist, AM630, or BCP + PPAR-γ antagonist, BADGE was started from the 9th week and continued till the 12th week. BCP significantly ameliorated all diet-induced alterations in a CB2R-dependant manner as it improved glycemic parameters, dyslipidemia, and vascular oxidative stress and inflammation. It also downregulated proatherogenic adhesion molecule (VCAM-1) and restored vascular eNOS/iNOS expression balance. PPAR-γ was involved in BCP-evoked suppression of vascular inflammation, VCAM-1 and restoration of normal vascular eNOS/iNOS balance thus normal NO level. Furthermore, part of BCP hypolipidemic effects (lowering total cholesterol, LDL, VLDL) involved both CB2R and PPAR-γ receptors. BCP treatment was superior to pioglitazone in anti-inflammatory and anti-atherosclerotic measures. BCP may represent a more potent alternate to pioglitazone avoiding its side effects in the treatment of insulin resistance and vascular inflammation.
Background:
Intracerebral hemorrhage (ICH) is a common neurological emergency with higher mortality and disability rate than cerebral ischemia. Although diverse therapeutic interventions have been explored for potential neuroprotection from ICH, no effective drugs until now are available for improvement of survival rate or the life quality of survivors after ICH. Just like cerebral ischemia, inflammatory mechanism is highly thought to play a vital role in hemorrhagic brain injury. Ligustilide (LIG) has potent anti-inflammatory effects, which were shown to be closely related to its neuroprotective effects against ischemic brain injury. Senkyunolide H (SH) and senkyunolide I (SI) are natural degradation products of LIG, which contain the mother nucleus structure of LIG as that of phthalide. However, no reports have been retrieved about the neuroprotective effects of the three phthalide compounds on ICH, especially from the perspectives of inflammatory pathways. Accordingly, this study investigated the neuroprotective potentials and mechanisms of LIG, SH and SI on experimental ICH in mice.
Methods:
ICH was induced in adult male CD-1 mice by intracerebral injection of autologous blood. LIG, SH and SI, respectively, was administrated after ICH induction. Neurological deficits, brain edema, injury volume, the number of surviving/dying neurons and inflammatory gene expression were evaluated at 3 days after ICH.
Results:
Neurological deficits, brain edema, neuronal injury, microglia and astrocytes activation as well as peripheral immune cells infiltration were all significantly improved by LIG and SH, yet SI not. Moreover, the expression of TLR4, p-NF-kB p65, TNF-α and IL-6, was significantly downregulated by LIG and SH treatment. So was Prx1 expression and release.
Conclusions:
LIG and SH provide the potent neuroprotective effects against hemorrhagic stroke by inhibiting Prx1/TLR4/NF-kB signaling and the subsequent immune and neuroinflammation lesions.
The exact mechanism of the migraine pathophysiology remained unclear. Although there are some reports showing low-grade inflammation in migraineurs, further studies are needed in this field. Thus, we designed a study to evaluate the serum levels of two main proinflammatory markers in migraine patients. In this case-control research, 43 migraine patients (23 chronic and 20 episodic migraineurs) and 40 age-sex-matched headache-free controls were studied. Demographic, dietary, and anthropometric data, headache characteristics, and serum C-reactive proteins (CRP) and tumor necrosis factor-alpha (TNF-α) assessments were collected. The mean ± SD age of the case and control groups were 36.98 ± 9.91 and 34.84 ± 9.75 years respectively. Compared to control subjects, both episodic and chronic migraineurs had significantly higher median levels of TNF-α (0.24, 0.95, and 1.90 pg/ml, respectively; P value < 0.001). Also, we observed a positive association between the TNF-α levels and the odds of having migraine after considering gender, age, body mass index, and dietary intakes of energy, carbohydrate, protein, fat, and mono and poly unsaturated fatty acids in the multivariable regression models (OR = 2.15; 95% CI 1.31–3.52; P value < 0.001). However, no significant association was demonstrated between migraine and serum CRP (OR = 2.91; 95% CI 0.87–9.78; P value = 0.08). These findings supported that inflammatory state could be related to the pathogenesis of migraine and it can thus be suggested that this effect might be beyond migraine progression. Further detailed studies are needed to investigate the importance of these findings in the pathogenesis of migraine headache.
Phytotherapy is a source of finding new remedies for migraine. Traditional chamomile oil (chamomile extraction in sesame oil) is a formulation in Persian medicine (PM) for pain relief in migraine. An oleogel preparation of reformulated traditional chamomile oil was prepared and then standardized based on chamazulene (as a marker in essential oil) and apigenin via gas chromatography (GC) and high-performance liquid chromatography (HPLC) methods, respectively. A crossover double-blind clinical trial was performed with 100 patients. Each patient took two tubes of drug and two tubes of placebo during the study. Visual analog scale (VAS) questionnaires were filled in by the patients and scores were given, ranging from 0 to 10 (based on the severity of pain) during 24 h. Other complications like nausea, vomiting, photophobia, and phonophobia were also monitored. There was 4.48 ± 0.01 μl/ml of chamazulene and 0.233 mg/g of apigenin in the preparation (by correcting the amount with extraction ratio). Thirty-eight patients in the drug-placebo and 34 patients in the placebo-drug groups (a total number of 72 patients as per protocol) completed the process in the randomized controlled trial (RCT). Adapted results from the questionnaires showed that pain, nausea, vomiting, photophobia, and phonophobia significantly (p < 0.001) decreased by using chamomile oleogel on the patients after 30 min. Results supported the efficacy of chamomile oleogel as a pain relief in migraine without aura.
Background:
Illness perception is significantly related to several outcome measures in different medical conditions. However, little is known about headache-related causal attributions and cognitive and emotional representations in patients with migraine.
Objective:
To examine perceived causes of headache and demographic, clinical, and psychological correlates and predictors of illness perception in patients with migraine attending a tertiary care headache centre.
Methods:
A sample of 143 patients with migraine (85.3% women, mean age 44.0 ± 12.1 years) completed the Brief Illness Perception Questionnaire (Brief IPQ), the Symptom Questionnaire (SQ), and the Migraine Disability Assessment (MIDAS) Questionnaire. A set of demographic and clinical characteristics was also collected.
Results:
Stress, heredity, and nervousness were the most frequent perceived causes of headache. Female gender was significantly related to higher Brief IPQ "consequences" and "emotional response" scores. Increased psychological distress and a poorer clinical course were significantly associated with more negative illness representations. In multiple regression analysis, a longer illness duration, increased depressive symptoms, and higher levels of headache-related disability and painfulness of headache attacks independently predicted a worse illness perception.
Conclusions:
In patients with migraine, depressive symptoms and a worse disease status, characterized by a longer history of suffering, higher disability and more painful headache attacks, may negatively affect illness perception. It could also be that dysfunctional illness representations lead to depressive symptoms and decrease patients' motivation to adhere to treatments, resulting in a worse outcome. Future studies should examine whether the improvement of illness perception through specific psychological interventions may promote a better adaptation to migraine.
Parkinson's disease (PD) is one of the most common neurodegenerative diseases resulting from the continuous death of dopaminergic neurons in substantia nigra. MPP+ (1-methyl-4-phenylpyridinium) has been reported to be a major neurotoxin causing neurotoxic insults on dopaminergic neurons in humans. β-Caryophyllene (BCP), an important cannabinoid derived from the essential oils of different species, has displayed pharmacological properties in different kinds of tissues and cells. However, neuroprotective effects of BCP in PD haven't been reported before. Our results indicate that treatment with MPP+ in SH-SY5Y cells led to a significant decrease in cell viability, which was restored by BCP. Additionally, BCP suppressed MPP+-induced release of lactic dehydrogenase (LDH) and the generation of reactive oxygen species (ROS). In contrast, BCP treatment restored the reduction in mitochondrial membrane potential (MMP) induced by MPP+. BCP treatment increased intracellular GSH and GPx activity. Also, we found that the antioxidant effects of BCP against MPP+- induced neurotoxicity are dependent on cannabinoid receptor type 2 (CB2R). Moreover, our results indicated that BCP prevented MPP+-induced apoptosis of SH-SY5Y through inhibiting the up-regulation of cleaved Caspase-3, Bax, and restoring the expression of Bcl-2. Besides, BCP markedly suppressed HO-1 activation and c-Jun N-terminal Kinase (JNK) phosphorylation. We conclude that BCP might act as a promising therapeutic agent against MPP+ toxicity in neuronal cells.
Nitric oxide (NO) is a small gaseous signaling molecule that has important biological effects. It has been heavily implicated in migraine; and the NO donor, nitroglycerin, has been used extensively as a human migraine trigger. Correspondingly, a number of components of the NO signaling cascade have been shown to be upregulated in migraine patients. NO is endogenously produced in the body by NO synthase (NOS), of which there are three isoforms: neuronal NOS (nNOS), endothelial NOS (eNOS), and inducible NOS (iNOS). Based on the accumulating evidence that endogenous NO regulation is altered in migraine pathogenesis, global and isoform-selective inhibitors of NOS have been targeted for migraine drug development. This review highlights the evidence for the role of NO in migraine and focuses on the use of NOS inhibitors for the treatment of this disorder. In addition, we discuss other molecules within the NO signaling pathway that may be promising therapeutic targets for migraine.
Although stress is one of the risk factors of diabetes, few studies have assessed the effects of stress on diabetic rats. This study therefore analyzed differences in cardiovascular-related factors among control, non-stressed diabetic, and stressed diabetic rats, as well as assessed the effects of linalyl acetate (LA) on stressed diabetic rats. Male Sprague-Dawley rats were subjected to immobilization stress throughout the entire experimental period, and diabetes was induced on day 15 by a single injection of streptozotocin. After confirming the induction of diabetes, stressed diabetic rats were administered LA (10 mg/kg or 100 mg/kg) or metformin (500 mg/kg) for the last 7 days. Compared with non-stressed diabetic rats, stressed diabetic rats had significantly lower body weight, body fat percentage, ACh-induced vasorelaxation, systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and NF-κB expression, as well as increased serum nitrite concentration. Although metformin increased serum insulin concentration significantly, LA 100 mg/kg showed only an increasing tendency. However, treatment with LA 100 mg/kg not only reduced serum glucose and NF-κB expression, but restored ACh-induced vasorelaxation, SBP, DBP, HR, AMP-activated protein kinase (AMPK) expression and serum nitrite almost to control levels. Importantly, LA 100 mg/kg was more effective than metformin in ameliorating serum glucose, eNOS expression, HR, and serum nitrite. These findings suggest that chronic stress can aggravate endothelial dysfunction and hemodynamic alterations in diabetes and that LA may have potent therapeutic efficacy in diabetic patients with cardiovascular disease complications or chronic stress.
Lavender essential oil (Lvn) has anti-inflammatory effects in an ovalbumin-sensitized murine model of asthma, and inhibits inflammatory cell infiltration into the lungs. The anti-inflammatory effects of Lvn on cell adhesion molecules are not clear. Here we evaluated the effects of Lvn and its main constituents, linalyl acetate (LA) and linalool (LO), on the expression of tumor necrosis factor-alpha (TNF-α)-induced cell adhesion molecules in murine brain endothelial bEnd.3 cells and human umbilical vein endothelial cells (HUVECs). The bEnd.3 cells were treated with Lvn, LA, or LO and subsequently stimulated with TNF-α. The mRNA expression levels of cell adhesion molecules were detected using RT-PCR. E-selectin and P-selectin protein and phosphorylated-NF-κB p65 were detected by western blotting. The effects of Lvn on HUVECs were measured by RT-PCR. In bEnd.3 cells, Lvn and LA suppressed TNF-α-induced E-selectin, P-selectin, vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and phosphorylated-NF-κB p65 in the nucleus; LO did not suppress P-selectin or phosphorylated-NF-κB p65. Lvn inhibited TNF-α-induced E-selectin mRNA in HUVECs. These results indicate that Lvn and LA inhibit TNF-α-induced cell adhesion molecules in endothelial cells through the suppression of NF-κB activation. Consequently, Lvn or other essential oils including LA may be useful as alternative anti-inflammatory medicines.
Air pollution is linked to increased emergency room visits for headache and migraine patients frequently cite chemicals or odors as headache triggers, but the association between air pollutants and headache is not well-understood. We previously reported that chronic environmental irritant exposure sensitizes the trigeminovascular system response to nasal administration of environmental irritants. Here, we examine whether chronic environmental irritant exposure induces migraine behavioral phenotypes. Male rats were exposed to acrolein, a TRPA1 agonist, or room air by inhalation for 4 days prior to meningeal blood flow measurements, periorbital cutaneous sensory testing or other behavioral testing. Touch-induced c-Fos expression in trigeminal nucleus caudalis was compared in animals exposed to room air or acrolein. Spontaneous behavior and olfactory discrimination was examined in open field testing. Acrolein inhalation exposure produced long-lasting potentiation of blood flow responses to a subsequent TRPA1 agonist and sensitized cutaneous responses to mechanical stimulation. C-Fos expression in response to touch was increased in trigeminal nucleus caudalis in animals exposed to acrolein compared to room air. Spontaneous activity in an open field and scent preference behavior were different in acrolein exposed compared to room-air exposed animals. Sumatriptan, an acute migraine treatment, blocked acute blood flow changes in response to TRPA1 or TRPV1 agonists. Pretreatment with valproic acid, a prophylactic migraine treatment, attenuated the enhanced blood flow responses observed after acrolein inhalation exposures. Environmental irritant exposure yields an animal model of chronic migraine in which to study mechanisms for enhanced headache susceptibility after chemical exposure.
Rhizoma Curcumae (RC) is perennial herbaceous plant mainly present in China, India and Malaysiabelong, which is belong to the family Zingiberaceae. The rhizomes of RC have been used as a famous traditional Chinese medicine for the treatment of syndrome of blood stasis. A selective, sensitive and accurate gas chromatography-mass spectroscopy (GC-MS) method was developed and validated in this paper for the simultaneous determination and pharmacokinetic study of α-Pinene, 1,8-Cineole, Borneol, β-Elemene, Curcumol, Germacrone, and Curdione in rat plasma. The GC-MS system was operated under selected ion monitoring (SIM) mode using a DB-5 (30m×0.25mm (ID)×0.25μm (film thickness)) column. Linearity, intra-day and inter-day precisions, accuracy, extraction recovery and stability were used to validate the current GC/MS assay. The lowest limit of quantifications (LLOQ) of α-Pinene, 1,8-Cineole, Borneol, β-Elemene, Curcumol, Germacrone, Curdione were 2.71ng/mL, 7.76ng/mL, 3.37ng/mL, 21.68ng/mL, 40.21ng/mL, 24.84ng/mL and 47.78ng/mL respectively. After oral administration 1.0g/kg of RC rhizomes to the rats, the maximum plasma concentration (Cmax) was 34.72±9.97ng/mL for α-Pinene, 99.86±5.54ng/mL for 1,8-Cineole, 16.10±3.37ng/mL for Borneol, 248.98±86.19ng/mL for β-Elemene, 673.75±104.15ng/mL for Curcumol, 2353.64±637.83ng/mL for Germacrone and 2420.04±708.51ng/mL for Curdione. The time to reach the maximum plasma concentration (Tmax) was 2.33±0.29h for α-Pinene, 0.67±0.29h for 1,8-Cineole, 1.33±0.58h for Borneol, 1.83±0.76h for β-Elemene, 0.83±0.29h for Curcumol, 0.89±0.98h for Germacrone and 1.17±0.76h for Curdione. In this study, a validated GC-MS method for simultaneous determination of seven volatile oil compounds in rat plasma after oral administration of the extract of RC rhizomes and research on their pharmacokinetics was validated. The recovery and stability results were satisfactory in this study.
β-elemene, extracted from Rhizoma zedoariae, has been widely used as a traditional medicine for its antitumor activity against a broad range of cancers. However, the effect of β-elemene in inflammation disorders has yet to be determined. The present study was designed to investigate the anti-inflammatory effects and potential molecular mechanisms of β-elemene in lipopolysaccharide (LPS)-induced murine macrophage cells RAW264.7. We found that the production of pro-inflammatory mediators, including interleukin-6(IL-6), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), induced by LPS was significantly suppressed by β-elemene in a dose-dependent manner in RAW264.7 macrophage cell line. Also, β-elemene inhibited LPS-induced nitric oxide synthase (iNOS) and interleukin-10 (IL-10) expression by RAW264.7, which was related to the down-regulation of Wnt/β-catenin signaling pathway. Importantly, this study demonstrates that β-catenin was significantly inhibited by β-elemene, which appeared to be largely responsible for the down-regulation of Wnt/β-catenin signaling pathway. Accordingly, the deletion of β-catenin in primary macrophages reversed β-catenin-elicited inhibition of immune response. Furthermore, β-catenin expression and Wnt/β-catenin signaling pathway induced by LPS in RAW264.7 was also significantly inhibited by α-humulene, one isomeric sesquiterpene of β-elemene. α-humulene was also found to significantly inhibit LPS-induced production of proinflammatory cytokines. However, α-humulene showed more cytotoxic ability than β-elemene. Collectively, our data illustrated that β-elemene exerted a potent inhibitory effect on pro-inflammatory meditator and cytokines production via the inactivation of β-catenin, and also demonstrated the protective functions of β-elemene in endotoxin-induced inflammation. β-elemene may serve as potential nontoxic modulatory agents for the prevention and treatment of inflammatory diseases.
The essential oil of Nepeta menthoides Boiss. & Bohse., from Iran, was analysed by GC/MS. Two types of multivariate analyses were done based on the chemical composition of the investigated sample in this study and 12 other samples reported in the literature to show the chemodiversity in essential oil composition. Antimicrobial, acetylcholinesterase inhibitory and cytotoxic activities of the essential oil and its major component were assessed. Twenty-one compounds were identified, representing 96.81% of the total oil and the major constituent was 1,8-cineole (70.06%). Multivariate analyses revealed two chemotypes, i.e. nepetalactone and 1,8-cineole. The essential oil of the sample investigated in this study which was a 1,8-cineole chemotype and 1,8-cineole showed moderate antimicrobial activity and significantly inhibited the activity of acetylcholinesterase enzyme. Cytotoxicity evaluation against three breast cancer cell lines showed a potent inhibitory activity. Further investigations are necessary to confirm the variety in several populations of N. menthoides.
Amyloid β (Aβ) is the major component of senile plaques (SP) in the brains of Alzheimer's disease (AD) patients, and serves as an inflammatory stimulus for microglia. Trans-caryophyllene (TC), a major component in the essential oils derived from various species of medicinal plants, has displayed its neuro-protective effects in previous studies. However, whether TC has a protective role in AD remains unknown. In this study, the effects of TC on Aβ1-42-induced neuro-inflammation were investigated. We found that TC reduced the release of LDH in BV-2 microglial cells treated with Aβ1-42. In addition, pretreatment of BV2 microglia with TC at concentrations of 10, 25, and 50μM prior to Aβ stimulation led to significant inhibition of nitric oxide (NO) and prostaglandin E2 (PGE2) production, expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and secretion of pro-inflammatory cytokines. Notably, our results indicate that TC remarkably attenuated Aβ1-42-activated overexpression of toll-like receptor 4 (TLR4). We further demonstrated that TC markedly reversed Aβ1-42-induced phosphorylation and degradation of IκBα, nuclear translocation of p65, and NF-κB transcriptional activity. These findings suggest that TC may have therapeutic potential for the treatment of AD.
Aim
To evaluate the effect of topical formulation of Rosa damascena Mill. (R. damascena) oil on migraine headache, applying syndrome diffrentiation model.
Methods and materials
Forty patients with migraine headache were randomly assigned to 2 groups of this double-blind, placebo-controlled cross-over trial. The patients were treated for the first 2 consecutive migraine headache attacks by topical R. damascena oil or placebo. Then, after one week of washout period, cross-over was done. Pain intensity of the patients' migraine headache was recorded at the beginnig and ten-sequence time schadule of attacks up to 24 h. In addition, photophobia, phonophobia, and nausea and/or vomitting (N/V) of the patients were recorded as secondary outcomes. Finally, gathered data were analysed in a syndrome differentiation manner to assess the effect of R. damascena oil on Hot- and Cold-type migraine headache.
Results
Mean pain intensity of the patients' migraine headache in the different time-points after R. damascena oil or placebo use, was not significantly different. Additionally, regarding mean scores of N/V, photophobia, and phonophobia severity of the patients, no significant differences between the two groups were observed. Finally, applying syndrome differentiation model, the mean score of migraine headache pain intensity turned out to be significantly lower in patients with “hot” type migraine syndrome at in 30, 45, 60, 90, and 120 min after R. damascena oil application compared to “cold” types (P values: 0.001, 0.001, <0.001, <0.001, and 0.02; respectively).
Conclusion
It seems that syndrome differentiation can help in selection of patients who may benefit from the topical R. damascena oil in short-term relief of pain intensity in migraine headache. Further studies of longer follow-up and larger study population, however, are necessitated for more scientifically rigorous judgment on efficacy of R. damascena oil for patients with migraine headache.
The aim of this study was to explore the chemical composition and the effect of essential oil of Angelicae dahuricae radix on a nitroglycerin (NTG)-induced rat model of migraine. The CO2 supercritical fluid extraction method was optimized for the extraction of essential oil of A. dahuricae radix (EOAD) and its chemical composition was determined. The migraine model was established by subcutaneous injection of NTG (10 mg/kg) 1 h after the last administration of EOAD. The therapeutic effect of EOAD and its underlying mechanism were assessed by monitoring behavioral changes, levels of nitric oxide (NO) in serum and brain tissues, plasma levels of calcitonin gene-related peptide (CGRP) and endothelin (ET), and ET/NO ratio. The optimal conditions for CO2 supercritical fluid extraction of EOAD, as determined by orthogonal test [L9(3(4))], were as follows: 2 h extraction time, 20 MPa pressure, 40°C temperature, and 30 mesh. The yield of EOAD was 1.8%. On gas chromatography-mass spectrometry, 45 peaks were found in EOAD, and 22 compounds were identified and quantified. The main constituents of EOAD were 1-dodecanol (13.71%), elemene (7.54%), palmitic acid ethyl ester (7.32%), α-pinene (6.25%), and 1-pentadecanol (6.08%). Compared with rat migraine model controls, EOAD (35, 70, and 140 mg/kg) significantly reduced the number of head shaking, head scratching, and hind leg shooting events, decreased serum and brain NO levels, decreased plasma CGRP, and increased ET levels in rats. ET/NO ratio was elevated to 28.68 in the EOAD high-dose group. EOAD ameliorates NTG-induced migraine in rats likely by modulating the levels of vasoactive substances.
Painful peripheral neuropathy is a common side effect of paclitaxel (PTX). The use of analgesics is an important component for management of PTX-induced peripheral neuropathy (PINP). However, currently employed analgesics have several side effects and are poorly effective. β-caryophyllene (BCP), a dietary selective CB2 agonist, has shown analgesic effect in neuropathic pain models, but its role in chemotherapy-induced neuropathic pain has not yet been investigated. Herein, we used the mouse model of PINP to show the therapeutic effects of BCP in this neuropathy. Male Swiss mice receiving PTX (2 mg kg⁻¹, ip, four alternate days) were treated with BCP (25 mg kg⁻¹, po, twice a day) either during or after PTX administration. Some groups were also pretreated with AM630 (CB2 antagonist, 3 mg kg⁻¹, ip) or AM251 (CB1 antagonist, 1 mg kg⁻¹, ip). Spinal cord samples were collected in different time points to perform immunohistochemical analysis. BCP attenuated the established mechanical allodynia induced by PTX (p < 0.0001) in a CB2-dependent manner. Of note, when given concomitantly with PTX, BCP was able to attenuate the development of PINP (p < 0.0001). Spinal cord immunohistochemistry revealed that preventive treatment with BCP reduced p38 MAPK and NF-κB activation, as well as the increased Iba-1 and IL-1β immunoreactivity promoted by PTX. Our findings show that BCP effectively attenuated PINP, possibly through CB2-activation in the CNS and posterior inhibition of p38 MAPK/NF-κB activation and cytokine release. Taken together, our results suggest that BCP could be used to attenuate the establishment and/or treat PINP.
Alpha-pinene is a key compound of the essential oils extracted from many species of coniferous trees. It is known for its biological activities. The aim of the present study was to determine the preventive effect of alpha-pinene on aspirin-induced toxicity in vitro, using IEC-6 cells, and to investigate its antioxidant activities. The antioxidant activities were determined by 1,1-diphenyl-2-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP). The cytotoxicity and oxidative stress were detected by cell viability, antioxidant enzyme activity, malondialdehyde (MDA) and GSH production, and the activation of MAPK pathways.
The results indicated that alpha-pinene revealed an important antioxidant activity. It was evaluated by DPPH test (EC50 = 310 ± 10 μg/mL) and FRAP test (EC50 = 238 ± 18.92 μg/mL). The co-exposure of alpha-pinene with aspirin on cells significantly increased the survival of cells and the level of GSH, and decreased the levels of MDA and total SOD and the activity of Mn-SOD. In addition, the activation of p38 and JNK was blocked by alpha-pinene. Therefore, these findings suggest that alpha-pinene can protect IEC-6 cells against aspirin-induced oxidative stress.
In this work, the anti-tumor constituent β-elemene was selectively separated from the volatile oil of the Curcumae Rhizoma by countercurrent chromatography with silver nitrate as selective reagent based on the formation of coordination complexes. A biphasic solvent system composed of n-hexane/methanol/water (2:1.5:0.5, v/v/v) was selected, in which 0.15 mol L(-1) of silver nitrate was added to the aqueous phase. The aqueous phase was used as the stationary phase for separation of β-elemene by countercurrent chromatography after it was partially purified from the volatile oil by silica gel column chromatography. An enriched β-elemene fraction was obtained by silica gel column chromatography to improve the percentage of β-elemene from 16.5 to 46.1%. Subsequently, β-elemene was further purified from 445 mg of the partially purified sample of volatile oil by countercurrent chromatography with silver nitrate as a selective reagent, yielding 145 mg of β-elemene with greater than 99% purity, as determined by gas chromatography-mass spectrometry. The recovery of β-elemene from the crude volatile oil through two steps was around 63.6%. This article is protected by copyright. All rights reserved.
Rationale:
Large-conductance calcium-activated potassium channels (BK) are composed of pore-forming BKα and auxiliary β1 subunits in arterial smooth muscle cells (myocytes). Vasoconstrictors, including endothelin-1 (ET-1), inhibit myocyte BK channels, leading to contraction, but mechanisms involved are unclear. Recent evidence indicates that BKα is primarily plasma membrane localized, whereas the cellular location of β1 can be rapidly altered by Rab11A-positive recycling endosomes. Whether vasoconstrictors regulate the multisubunit composition of surface BK channels to stimulate contraction is unclear.
Objective:
Test the hypothesis that ET-1 inhibits BK channels by altering BKα and β1 surface trafficking in myocytes, identify mechanisms involved, and determine functional significance in myocytes of small cerebral arteries.
Methods and results:
ET-1, through activation of PKC (protein kinase C), reduced surface β1 abundance and the proximity of β1 to surface BKα in myocytes. In contrast, ET-1 did not alter surface BKα, total β1, or total BKα proteins. ET-1 stimulated Rab11A phosphorylation, which reduced Rab11A activity. Rab11A serine 177 was identified as a high-probability PKC phosphorylation site. Expression of a phosphorylation-incapable Rab11A construct (Rab11A S177A) blocked the ET-1-induced Rab11A phosphorylation, reduction in Rab11A activity, and decrease in surface β1 protein. ET-1 inhibited single BK channels and transient BK currents in myocytes and stimulated vasoconstriction via a PKC-dependent mechanism that required Rab11A S177. In contrast, NO-induced Rab11A activation, surface trafficking of β1 subunits, BK channel and transient BK current activation, and vasodilation did not involve Rab11A S177.
Conclusions:
ET-1 stimulates PKC-mediated phosphorylation of Rab11A at serine 177, which inhibits Rab11A and Rab11A-dependent surface trafficking of β1 subunits. The decrease in surface β1 subunits leads to a reduction in BK channel calcium-sensitivity, inhibition of transient BK currents, and vasoconstriction. We describe a unique mechanism by which a vasoconstrictor inhibits BK channels and identify Rab11A serine 177 as a modulator of arterial contractility.
Cancer is a major problem in public health and is one of the leading causes of mortality worldwide. Many types of cancer cells exhibit aberrant cellular signal transduction in response to stress, which often leads to oncogenesis. Mitogen-activated protein kinase (MAPK) signal cascades are one of the important intracellular stress signaling pathways closely related to cancer. The key molecules in MAPK signal cascades that respond to various types of stressors are apoptosis signal-regulating kinase (ASK) family members; ASK1, ASK2 and ASK3. ASK family members are activated by a wide variety of stressors, and they regulate various cellular responses, such as cell proliferation, inflammation and apoptosis. In this review, we will discuss both the oncogenic and anti-oncogenic roles of the ASK family members in various contexts of cancer development with deeper insights into the involvement of ASK family members in cancer pathology.
Multiple sclerosis is the most common autoimmune inflammatory and demyelinating disease of the central nervous system. The experimental autoimmune encephalomyelitis (EAE) is an appropriate and a well-establish model for studying the pathogenesis of MS. β-caryophyllene (BCP), a natural sesquiterpene found in many plant species, is a potent anti-inflammatory compound. Herein we investigated the in vitro and in vivo immunomodulatory effects of BCP on C57BL/6 mice induced with EAE. BCP was in vitro evaluated (4, 20, and 40 μM) on splenocytes obtained from EAE-induced C57BL/6 mice, and in vivo (25 or 50 mg/kg/day) orally administered on EAE-mice. The clinical course, body weight, cytokines and oxygen radicals production were investigated in C57BL/6 EAE-mice. In vitro and in vivo immunological responses were evaluated by ELISA, and CNS sections were stained by hematoxylin and eosin methods The in vitro production of H2O2, NO, IFN-γ, and TNF- α was inhibited by BCP (20 and 40 μM) in cultured cells from EAE-mice. BCP (25 and 50 mg/kg/day) reduced clinical score and severity of EAE and inhibited H2O2, NO, TNF-α, IFN-γ and, IL-17 production. EAE-mice, orally treated with BCP (mainly at 50 mg/kg/day), displayed levels of cytokines and clinical signs similar to animals with no EAE disease, demonstrating the therapeutic action of BCP on EAE animals. Histopathological and histomorphometric analysis confirmed that BCP treatment significantly reduced the numbers of inflammatory infiltrates and attenuated neurological damages in the CNS of EAE-mice.