ArticleLiterature Review

Essential oils and its bioactive compounds modulating cytokines: A systematic review on anti-asthmatic and immunomodulatory properties

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  • Centro Universitário AGES | University Center AGES
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Abstract

Background: Asthma, the main inflammatory chronic condition affecting the respiratory system, is characterized by hyperresponsiveness and reversible airway obstruction, recruitment of inflammatory cells and excessive production of mucus. Cytokines as biochemical messengers of immune cells, play an important role in the regulation of allergic inflammatory and infectious airway processes. Essential oils of plant origin are complex mixtures of volatile and semi volatile organic compounds that determine the specific aroma of plants and are categorized by their biological activities. Purpose: We reviewed whether essential oils and their bioactive compounds of plant origin could modulate cytokines' immune responses and improve asthma therapy in experimental systems in vitro and in vivo. Methods: Electronic and manual search of articles in English available from inception up to November 2018 reporting the immunomodulatory activity of essential oils and their bioactive compounds for the management of asthma. We used PubMed, EMBASE, Scopus and Web of Science. Publications reporting preclinical experiments where cytokines were examined to evaluate the consequence of anti-asthmatic therapy were included. Results: 914 publications were identified and 13 were included in the systematic review. Four articles described the role of essential oils and their bioactive compounds on bronchial asthma using cell lines; nine in vivo studies evaluated the anti-inflammatory efficacy and immunomodulating effects of essential oil and their secondary metabolites on cytokines production and inflammatory responses. The most important immunopharmacological mechanisms reported were the regulation of cytokine production, inhibition of reactive oxygen species accumulation, inactivation of eosinophil migration and remodeling of the airways and lung tissue, modulation of FOXP3 gene expression, regulation of inflammatory cells in the airways and decreasing inflammatory mediator expression levels. Conclusion: Plant derived essential oils and related active compounds have potential therapeutic activity for the treatment of asthma by modulating the release of pro-inflammatory (TNF-α, IL-1β, IL-8), Th17 (IL-17), anti-inflammatory (IL-10), Th1 (IFN-γ, IL-2, IL-12) and Th2 (IL-4, IL-5, IL-6, IL-13) cytokines and the suppression of inflammatory cell accumulation.

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... This has resulted in the search for new therapeutic strategies, often represented by natural products. In this context, essential oils (EOs), aromatic plant secondary metabolites, are increasingly gaining attention as anti-inflammatory agents [33][34][35]. ...
... Commercially, they have a wide range of applications in the fragrance and cosmetic industries, as well as in food and pharmaceutical industries. EO use in human health is linked to their biological properties, which have numerous applications [20,21,[34][35][36][40][41][42][43]. Those of Citrus EOs have been recently reviewed [5,33], among which the anti-inflammatory action of BEO has been already reported [44], albeit without investigating the mechanism. ...
... It is known that the levels of some pro-inflammatory cytokines, such as IL-1β, IL-6, and TNF-α, increase during CAR-induced edema, playing a pivotal role in the onset and perpetuation of the inflammatory process [46], thus representing important targets for developing new antiinflammatory drugs. In line with other research demonstrating the ability of EOs to modulate these pro-inflammatory cytokines [34,47,48], in our study, BEO-FF reduced the levels of up-mentioned cytokines in the paw homogenates, thereby suggesting a possible mechanism underlying BEO-FF anti-inflammatory activity. In addition, NO and PGE2, generated by nitric oxide synthases (NOS) and cyclooxygenase (COX), respectively, are key pro-inflammatory mediators that are widely implicated in inflammatory diseases [49], hence the inhibition of NO and PGE2 release being one of the main mechanisms through which EOs exert their anti-inflammatory activity [50]. ...
Article
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Renewed interest in natural products as potential source of drugs led us to investigate on both the anti-inflammatory and anti-nociceptive activity of Citrus bergamia Risso et Poiteau (bergamot) essential oil (BEO). Carrageenan-induced paw edema in rats was used as an experimental model of inflammation. Because of the toxicity of furocoumarins, we performed our study by using the BEO fraction deprived of these compounds (BEO-FF). Treatment with BEO-FF led to a significant inhibition of paw edema induced by a sub-plantar injection of carrageenan. Moreover, histological examination of BEO-FF-treated rat paw biopsies showed a reduction of pathological changes typical of edema. Pre-treatment with BEO-FF significantly reduced interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α levels in the paw homogenates, as well as nitrite/nitrate and prostaglandin E2 (PGE2) content in exudates. In addition, BEO-FF possesses antioxidant properties, as determined by cell-free assays. Furthermore, results of the writhing test showed that BEO-FF elicited a pronounced analgesic response, as demonstrated by a significant inhibition of constrictions in mice receiving acetic acid, with respect to control animals, whereas the results of the hot plate test suggested that the supra-spinal analgesia participates in the anti-nociceptive effect of BEO-FF. Our study indicates that BEO-FF exerts anti-inflammatory and anti-nociceptive effects, and suggests its potential role as an anti-edemigen and analgesic drug.
... Anti-inflammatory drugs, antihistamines, or anti-leukotriene drugs are prescribed and used as therapeutic agents for inflammatory and allergic diseases. In addition, recent studies have been performed on anti-allergy compounds from natural substances that effectively prevent skin aging and inflammatory diseases, such as atopic dermatitis, due to the increasing interest in healthy aging due to the increase in the aging population [7][8][9]. ...
... Anti-inflammatory drugs, antihistamines, or anti-leukotriene drugs are prescribed and used as therapeutic agents for inflammatory and allergic diseases. In addition, recent studies have been performed on anti-allergy compounds from natural substances that effectively prevent skin aging and inflammatory diseases, such as atopic dermatitis, due to the increasing interest in healthy aging due to the increase in the aging population [7][8][9]. Zizania latifola (Gramineae) is a wild rice plant from Asia that belongs to the Zizania genus. Z. latifolia grains have strong biological effects, such as hyperlipidemia suppression [10], the ability to eliminate oxidative stress from cells [11], blood glucose level suppression [12], insulin resistance improvement [12], and anti-obesity [10]. ...
Article
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Tricin, a flavone belonging to the Gramineae family, has been confirmed to be the primary compound in a Zizania latifolia extract (ZLE) that prevents allergies. Various allergic reactions occur because of the unbalanced differentiation of T help cells (Th) and the consequent overproduction of IgE. Therefore, the regulation of Th1 and Th2 responses by T helper cell differentiation is essential for suppressing allergic responses. This study confirmed the immunomodulatory effects of ZLE and the major compound tricin in an OVA-sensitized mouse model. The IgE and OVA-specific production of tricin and ZLE in plasma were investigated in OVA-sensitized mice. The effects of tricin and ZLE on the amount of Th1 and Th2 cytokines and transcription factors released in splenocytes were investigated in OVA-sensitized mice. The skin roughness and the number of mast cells were confirmed by staining the skin surface with H&E and toluidine blue. Tricin and ZLE reduced the plasma IgE and OVA-specific-IgE levels significantly compared to the OVA group. On the other hand, tricin and ZLE promoted the release of the Th1 cytokines IL-12 and IFN-γ and inhibited the release of Th2 cytokines (IL-4, -10, -13, and -5) in OVA-sensitized mice. Tricin and ZLE induced T-bet and NFATc2 expression, and-down regulated GATA-3 levels. The skin roughness and the number of mast cells decreased in the OVA-immunized mice. Overall, the data indicate that tricin and ZLE may prevent allergy-related diseases through immunomodulation.
... Among all these therapeutic approaches, natural products, mainly essential oils (EOs) have drawn much interest because of their robust use as anti-inflammatory, immunomodulator, and antioxidant as well as a source of novel antimicrobial, anti-inflammatory, and immunomodulator agents (Allegra et al., 2014;Sadgrove and Jones, 2019). EOs are well recognized for their strong antiviral, anti-inflammatory, and immunomodulatory activities (de Lavor et al., 2018;Asif et al., 2020;Gandhi et al., 2020). EO displays numerous beneficial effects in different diseases and produces systemic effects, consequently, it has been proposed as a possible candidate for evaluation in prevention and treatment of COVID-19 (Agatonovic-Kustrin et al., 2019). ...
... They have been consumed via diets and recognized for potent antioxidant, antiinflammatory, immunomodulatory, and antimicrobial properties (Aziz et al., 2018). Numerous experimental studies along with some clinical trials showed that EOs could be important therapeutic agents for immune system-related diseases (de Lavor et al., 2018;Gandhi et al., 2020). EOs supplementation along with other compounds are also very well recognized for their activity against bacteria and viruses that lead to respiratory infections. ...
Article
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The recent outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) started in December 2019, resulting in the coronavirus disease-19 (COVID-19) pandemic. Coronaviruses are solely accountable for rising mortality and socioeconomic saddles. Presently, there are few repurposed drugs such as remdesivir or favipiravir approved for the treatment of COVID-19, although vaccines and plasma therapy is also subject to emergency approval. However, some potential natural treatments and cures have also been proposed. Molecules of natural origin showed therapeutic importance such as antiviral, anti-inflammatory, and antioxidant activity, and could be useful drug candidates for treating COVID-19. In recent years, essential oils have shown promising therapeutic effects against many viral diseases. Carvacrol is one of the monoterpene phenol with abundant presence in essential oils of many aromatic plants, including thyme and oregano. It is being used as food flavoring, additive, and preservatives. Carvacrol is also used as a fragrance in cosmetic products. A number of research studies have shown biological actions of carvacrol with its therapeutic potential is of clinical significance. The in vitro and in vivo studies have shown multiple pharmacological properties such as anticancer, anti-fungal, anti-bacterial, anti-oxidant, anti-inflammatory, vasorelaxant, hepatoprotective, and spasmolytic. This review highlights the various biological and pharmacological properties of carvacrol within the scope of COVID-19.
... While both classes comprise phenolic compounds, their primary metabolic precursors and biosynthesis pathways are different. Specifically, terpenoids are synthesized via the mevalonate and mevalonate-independent pathways, while phenylpropanoids involve the shikimate pathways [28,38,46]. Furthermore, the volatile compounds found in EOs can be categorized based on their chemical classes, namely phenols, aldehydes, ketones, amines, amides, alcohols, and esters [25]. ...
... The therapeutic effects of EOs are manifested through the composition and concentration of these compounds. Therefore, they can exhibit a plethora of bioactive properties, including cardioprotective, hepatoprotective, neuroprotective, anxiolytic, antioxidant, anti-inflammatory, anticancer, anti-diabetic, anti-hyperpigmentation, antiviral, antifungal, antibacterial, antibiofilm, and acaricidal ( Figure 1) [26,38,46,47]. activity of EOs are illustrated in Figure 2 [25,42]. ...
Article
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Essential oils (EOs) have attracted considerable interest in the past few years, with increasing evidence of their antibacterial, antiviral, antifungal, and insecticidal effects. However, as they are highly volatile, the administration of EOs to achieve the desired effects is challenging. Therefore, nanotechnology-based strategies for developing nanoscaled carriers for their efficient delivery might offer potential solutions. Owing to their biocompatibility, biodegradability, low toxicity, ability to target a tissue specifically, and primary structures that allow for the attachment of various therapeutics, magnetite nanoparticles (MNPs) are an example of such nanocarriers that could be used for the efficient delivery of EOs for antimicrobial therapies. The aim of this paper is to provide an overview of the use of EOs as antibacterial agents when coupled with magnetite nanoparticles (NPs), emphasizing the synthesis, properties and functionalization of such NPs to enhance their efficiency. In this manner, systems comprising EOs and MNPs could offer potential solutions that could overcome the challenges associated with biofilm formation on prosthetic devices and antibiotic-resistant bacteria by ensuring a controlled and sustained release of the antibacterial agents.
... It would be opportune to note that the USA remains the leading country in terms of corona-related deaths (104,383), even overtaking China (4,638). Other countries reporting significant deaths include the UK (38,489), Italy (33,415), Brazil (29,314), France (28,802), Spain (27,127), Mexico (9,930), Belgian (9,467), Germany (8,511), Iran (7,797), India (5,394), Turkey (4,540), Peru (4,506), and Russia (4,693) (Fig. 3). ...
... pyramidalis EO SARS-CoV Antiviral efficacy [122] Juniperus oxycedrus ssp. oxycedrus EO SARS-CoV High antiviral efficacy [122] Laura nobilis EO SARS-CoV High antiviral efficacy [122] Nigella sativa EO CoV Good viral load decrease [123] Found in Rosmarinus officinalis, Syzygium aromaticum and other EO Betulinic acid SARS-CoV Inhibits SARS-CoV 3CL protease [138] Salvia officinalis EO SARS-CoV Antiviral efficacy [122] Thuja orientalis EO SARS-CoV High antiviral efficacy [122] cell accumulation [127]. EOs have also proven to be successful in clinical practice with inflammatory respiratory illness and have an important role in clinical therapy [126]. ...
Article
The World Health Organisation (WHO) announced on the 11th March 2020, a pandemic caused by a novel beta-coronavirus SARS-CoV-2, designated COVID-19. The virus emerged in December 2019 in Wuhan, China has spread across the world to be classed as a global pandemic. The traditional use of medicines from plants can be traced back to 60,000 years. Global interest in development of drugs from natural products has increased greatly during the last few decades. Essential oils (EOs) have been studied through the centuries and are known to possess various pharmaceutical properties. In the present review, we have highlighted the current biology, epidemiology, various clinical aspects, different diagnostic techniques, clinical symptoms, and management of COVID-19. An overview of the antiviral action of EOs along with their proposed mechanism of action and in silico studies conducted, are described. The reported studies of EOs antiviral activity highlight the baseline data about the additive, and/or synergistic effects among primary or secondary phytoconstituents found in individual oils, combinations or blends of oils and between EOs and antiviral drugs. It is hoped that further research will provide better insights of EOs potential to limit viral infection and aids in providing a solutions through natural, therapeutically active agents. lupus erythematosus; SKP2, s-phase kinase-associated protein 2; TNF-, tumour necrosis factor alpha; TPA, Tetradecanoyl-phorbol acetate; WHO, The World Health Organisation.
... Furthermore, the promising antimicrobial activity of EOs has led researchers to use them in association with antimicrobial drugs in order to reduce toxicity, side effects, and microbial resistance. Several EOs are generally recognized as safe, do not accumulate in the liver or kidneys, can stimulate the immune system [3][4][5], and cause no resistance, since microbes are unable to adapt to their heterogeneous structures [6]. Mentha x piperita L. (peppermint) EO is one of the most widely produced and consumed EOs. ...
... In this study, "Mentha of Pancalieri" EO exhibited higher antimicrobial activity towards C. neoformans, S. cerevisiae, and P. carsonii and displayed good antimicrobial activity towards C. krusei and C. glabrata-species that are often resistant to conventional drugs. This antifungal activity towards yeast strains is probably consistent with that of Mentha x piperita L. EO that is able to carry out anticandidal activity with consequent cell "death" by decreasing the amount of ergosterol and producing intracellular acidification following PM-ATPase inhibition [4]. Recent studies have shown that Mentha x piperita L. EO inactivates S. cerevisiae, a species that deteriorates fruit juices through the disorder of several physiological functions, i.e., enzymatic activity, efflux pump activity, and early apoptosis [20]. ...
Article
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The promising antimicrobial activity of essential oils (EOs) has led researchers to use them in combination with antimicrobial drugs in order to reduce drug toxicity, side effects, and resistance to single agents. Mentha x piperita, known worldwide as “Mentha of Pancalieri”, is produced locally at Pancalieri (Turin, Italy). The EO from this Mentha species is considered as one of the best mint EOs in the world. In our research, we assessed the antifungal activity of “Mentha of Pancalieri” EO, either alone or in combination with azole drugs (fluconazole, itraconazole, ketoconazole) against a wide panel of yeast and dermatophyte clinical isolates. The EO was analyzed by GC-MS, and its antifungal properties were evaluated by minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) parameters, in accordance with the CLSI guidelines, with some modifications. The interaction of EO with azoles was evaluated through the chequerboard and isobologram methods. The results suggest that this EO exerts a fungicidal activity against yeasts and a fungistatic activity against dermatophytes. Interaction studies with azoles indicated mainly synergistic profiles between itraconazole and EO vs. Candida spp., Cryptococcus neoformans, and Trichophyton mentagrophytes. Thus, the “Mentha of Pancalieri” EO may act as a potential antifungal agent and could serve as a natural adjuvant for fungal infection treatment.
... Immunomodulatory agents modify the response of the immune system by either increasing (immunostimulators) or decreasing (immunosuppressives) immune response [17][18][19]. The immunomodulatory agents have a broad range of biological effects, having applications and use in several fields of medicine among which are allergic eye diseases [17][18][19]. ...
... Immunomodulatory agents modify the response of the immune system by either increasing (immunostimulators) or decreasing (immunosuppressives) immune response [17][18][19]. The immunomodulatory agents have a broad range of biological effects, having applications and use in several fields of medicine among which are allergic eye diseases [17][18][19]. Immunomodulatory agents have changed the treatment protocols for many diseases where immune functions play a central role. ...
Article
PURPOSE OF REVIEW: The spectrum of allergic eye diseases includes a variety of conditions, each characterized by complex immunopathologies.Antiallergic drugs, such as antihistamines and mast cell stabilizers, are often insufficient without concomitant topical corticosteroid treatment. The chronic course of the more severe allergic eye diseases, such as vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC), limits the treatment with topical corticosteroids to short courses. In addition, topical corticosteroid treatment puts patients at high risk of developing severe ocular complications, particularly during childhood when VKC most frequently occurs.The immunopathology of chronic diseases, such as VKC and AKC, involves predominantly T lymphocytes, and as such, immunomodulators that inhibit T-cell activation seem to be the appropriate treatment for these chronic diseases. In the past years, there is an increased incidence of managing chronic allergic eye diseases with the immunomodulator tacrolimus. The current review presents an update of the recent clinical experience with topical tacrolimus for the management of chronic allergic eye diseases. RECENT FINDINGS: Topical tacrolimus significantly improves the symptoms and signs of the various forms of chronic allergic eye disease. Recent studies also demonstrate the efficacy of low concentrations of topical tacrolimus for VKC.Early medical treatment with topical tacrolimus can also prevent the development of serious ocular complications of VKC, such as shield ulcers or limbal stem cell deficiency. SUMMARY: Topical tacrolimus has significantly changed the management approaches in severe and chronic allergic eye diseases and has minimized the need for topical corticosteroids.
... Aromatherapy is a branch of CAM that introduces essential oils into the body to prevent and manage illnesses by means of numerous methods of administration: commonly massage, local application or breathing in of fragrant oils (Ali et al., 2015). Several pharmacological activities of essential oils have been investigated and reported; these activities include antioxidant, antibacterial, anticarcinogenic, anti-inflammatory, anxiety alleviating, analgesic, antidiabetic and antidepressant (Bakkali et al., 2008;Bhalla et al., 2013;de Lavor et al., 2018;de Sousa et al., 2015;Edris, 2007;Gandhi et al., 2020;Horváth & Ács, 2015). Clinical validation on the immunomodulatory effects of essential oils is relatively incomplete; however, there seems to be a possibility for certain essential oils to be capable of increasing the number of immune functions. ...
Chapter
Aromatherapy or essential oil therapy is an organic and botanical way of treating an individual’s body, mind and soul. Numerous prehistoric civilisations such as China, India and Egypt utilised this famous modality under CAM for around 6,000 years. It has proven to be effective for the management of lots of diseases and their complications. A survey of various research studies shows that aromatherapy has attained great attention in the last part of the 20th century and got quite famous in the 21st century because of its beneficial effects. The specialists of psychoneuroimmunology established that anxiety, stress and depression distress the immune system’s defensive and balancing functions, whereas healing with these oils is acknowledged to alleviate stress, invigorate and revive the person; not only this but these oils have well-established antiviral, antifungal, antimicrobial, antiseptic and anti-inflammatory properties. These days, there is an amplified tendency to utilise this healing mode to manage sleep disorders and cancer. This chapter will illuminate the history of aromatherapy and its application in different traditional systems of medicine, how this therapy affects psychoneuroimmunological systems of the body, types of aromatherapy, the role of essential oils in infectious diseases and for enhancing immunity and the role of aroma science healing in reducing stress, anxiety, depression and insomnia.
... Plant-derived essential oils and their associated active compounds are involved in immune modulation by modulating the release of proinflammatory, antiinflammatory, Th1 and Th2 cytokines, and suppression of inflammatory cell accumulation (Gandhi et al., 2020). Bioactive peptides in soybeans show immune-stimulating, antihypertensive, anti-amnestic, antithrombotic, and antioxidant activities. ...
Chapter
The immune system protects the organism against infections, cleans damaged cells and tissue, and eyes malignant cells that can occur in the body under constant surveillance. With age, an unstable state of immune response (immunosenescence) and chronic, low-grade inflammation (inflammaging) contribute to the pathogenesis of many age-related diseases. Immune system modulation is the process that involves modification of the immune response and/or the functioning of the immune system by the action of immunomodulators to prevent cell and tissue damage resulting from an excessive response. Recent studies have shown that plant bioactive molecules may play an important role in antiaging interventions by protecting or improving immune functions. This chapter focuses on the role of plant-derived bioactive molecules in immune modulation and their role in antiaging.
... Therefore, the EOs of thyme are widely applied in hygiene and skincare products such as cologne water, toothpaste, mouthwashes, deodorants, shampoos, soaps, bathing essences, shower gels and hair lotions. Gandhi et al. (2019) reviewed the scientific literature to determine whether plant-derived EOs and their bioactive compounds could relieve asthma through regulating cytokine immune responses under in vivo and in vitro conditions. After a systematic review of the most relevant articles (13 out of 914), it was concluded that these materials had sustained therapeutic effects for asthma treatment by regulating the release of anti-inflammatory (IL-10), Th1 (IFN-γ, IL-2, IL-12), Th2 (IL-4, IL-5, IL-6, IL-13), and pro-inflammatory (TNF-α, IL-1β, IL-8), Th17 (IL-17) cytokines and inflammatory responses through modulation of inflammatory cells in lungs and airways. ...
Article
Introduction Mint (Mentha spp.) and thyme (Thymus spp.) are two of the foremost aromatic herbs used in food and beverage products for their flavor, aromatic and medicinal qualities. These species belong to the tribe Mentheae, part of the mint family (Lamiaceae), which comprises many genera of well-known culinary and medicinal herbs. This review examines the phenolics in mint and thyme as natural health-promoting phytochemicals and potential antimicrobial drugs. Compounds examined here include carvacrol, thymol, p-cymene, carvone, menthol, menthone, pulegone, limonene, 1,8-cineole and cinnamaldehyde. Methods Literature searches were performed using nine databases to obtain peer-reviewed studies on the phytochemical complements of mint and thyme and the properties of individual bioactive compounds. Results The medicinal benefits of mint and thyme include their digestive, antiseptic, antispasmodic, antirheumatic, expectorant, antiallergic, antitussive, antioxidant and antimicrobial activities. Essential oils of these aromatic plants are utilized for a wide variety of applications, such as to impart fragrance and flavoring to cosmetics and spice mixtures, and as components of repellents and pesticides. Phenolic compounds, comprising phenols and polyphenols, are the most abundant secondary metabolites in the extracts and essential oils of mint and thyme. Discussion/Conclusions It was concluded from the literature that only a limited number of the phytochemical activities of mint and thyme have been explored, and that further interdisciplinary research efforts into the biological and molecular mechanisms of these compounds is likely to yield important findings in herbal medicine.
... A study reported by Gandhi et al. found that carvacrol also regulates cytokine production, inhibits ROS accumulations, and inactivates eosinophils migration lungs. EO suppressed cytokine production, pro-inflammatory and anti-inflammatory mediators formation, and accumulation (Gandhi et al., 2020). ...
Article
Full-text available
Carvacrol is a major natural constituent and is significantly present as an essential oil in aromatic plants and is well known for its numerous biological activities. Therapeutic properties of carvacrol have been demonstrated as anti-oxidant, anticancer, diabetes prevention, cardioprotective, anti-obesity, hepatoprotective and reproductive role, antiaging, antimicrobial, and immunomodulatory properties. The carvacrol biosynthesis has been mediated through mevalonate pathway. Carvacrol has the anticancer ability against malignant cells via decreasing the expressions of matrix metalloprotease 2 and 9, inducing apoptosis, enhancing the expression of pro-apoptotic proteins, disrupting mitochondrial membrane, suppressing extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase signal transduction, and also decreasing the phosphoinositide 3-kinase/protein kinase B. It also decreased the concentrations of alanine aminotransferase, alkaline phosphatase and aspartate aminotransferase, and gamma-glutamyl transpeptidase as well as also restored liver function, insulin level, and plasma glucose level. Carvacrol also has been found to exert antimicrobial activity against Staphylococcus aureus, Pseudomonas aeruginosa, Coagulase-negative staphylococcus, Salmonella spp., Enterococcus sp. Shigella, and Escherichia coli. The current review article summarizes the health-promoting perspectives of carvacrol through various pathways.
... A study reported by Gandhi et al. found that carvacrol also regulates cytokine production, inhibits ROS accumulations, and inactivates eosinophils migration lungs. EO suppressed cytokine production, pro-inflammatory and anti-inflammatory mediators formation, and accumulation (Gandhi et al., 2020). ...
Article
Full-text available
Carvacrol is a major natural constituent and is significantly present as an essential oil in aromatic plants and is well known for its numerous biological activities. Therapeutic properties of carvacrol have been demonstrated as anti‐oxidant, anticancer, diabetes prevention, cardioprotective, anti‐obesity, hepatoprotective and reproductive role, antiaging, antimicrobial, and immunomodulatory properties. The carvacrol biosynthesis has been mediated through mevalonate pathway. Carvacrol has the anticancer ability against malignant cells via decreasing the expressions of matrix metalloprotease 2 and 9, inducing apoptosis, enhancing the expression of pro‐apoptotic proteins, disrupting mitochondrial membrane, suppressing extracellular signal‐regulated kinase 1/2 mitogen‐activated protein kinase signal transduction, and also decreasing the phosphoinositide 3‐kinase/protein kinase B. It also decreased the concentrations of alanine aminotransferase, alkaline phosphatase and aspartate aminotransferase, and gamma‐glutamyl transpeptidase as well as also restored liver function, insulin level, and plasma glucose level. Carvacrol also has been found to exert antimicrobial activity against Staphylococcus aureus, Pseudomonas aeruginosa, Coagulase‐negative staphylococcus, Salmonella spp., Enterococcus sp. Shigella, and Escherichia coli. The current review article summarizes the health‐promoting perspectives of carvacrol through various pathways. Carvacrol is a major natural constituent in applauded for their nutraceutical potential ranging from antioxidant to anticancer
... These compounds have protective effects, bioactive, anticancer, antioxidant, anti-inflammatory properties, antiviral and antibacterial activities. In addition, QS inhibitory properties have been reported in some Gramnegative microorganisms, such as P. aeruginosa [12][13][14][15][16] . ...
Article
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Search inhibitors of Quorum Sensing (QS) in Pseudomonas aeruginosa are challenging to find therapies due to the broad antibiotic resistance. Therefore, this study aimed to probe ten aromatic compounds as inhibitors of three transcriptional regulators of QS in P. aeruginosa. The methodology consisted in determining the Binding Gibbs Energy (BGE) with software Chimera (tool vina) and Mcule, comparing the averages by the Tukey method (p≤0.05) to find inhibitors of QS. Subsequently, the LD50 in the mice model was evaluated by three QSAR models, and the in silico pharmacokinetic values were obtained from the ADME (the absorption distribution metabolism excretion) and PubChem databases. Found three potential inhibitors of RhlR with the lower BGE values in the range -6.70±0.21 to -7.43±0.35 kcal/mol. On the other side, all compounds were acceptable for Lipinski's rule of fives and the in silico oral mice LD50 and ADME values. Concluding, the ferulic acid and eugenol showed the best total BGE values (-75.07±0.892 and -70.36±1.022 kcal/mol), proposing them as a new therapy against the virulence of P. aeruginosa. Finally, the in silico studies have demonstrated are reproducible and valuable for putative QS inhibitors predicting and obtaining new studies derivatives from the results obtained in the present study. • The key benefits of this methodology are: Use free, licensed, flexible, and efficient software for in silico molecular docking. • Validation and comparison of BGE employing two molecular docking software in three different proteins. • Use classical molecular dynamics to define the stability and the total BGE of interaction protein-ligand and find the best inhibitor of a protein for proposing them as a possible therapy against the virulence of specific pathogens.
... Essential oils are used mainly through diffusion through the medium of aromatherapy lamps or are applied topically, by massage, diluted in a vegetable oil. There are studies [19] done on their effectiveness in various respiratory diseases, especially in adults, the pediatric bibliography being poorer. We should mention here a case [20] of a 3-year-old child under oxygen therapy for a respiratory syncytial virus pneumonia who benefited from aromatherapy. ...
Article
Herbal medicine is a mild and well-tolerated alternative treatment method that could be used to treat pediatric respiratory ailments. Medicinal plants such as captalan, geranium, turmeric or echinacea have been shown in numerous studies to have the ability to significantly improve the respiratory function of pediatric patients and may thus be a viable alternative to conventional treatments in acute and chronic respiratory diseases.
... EOs are applied in different industries due to their multi-activity properties (viz. anti-platelet activity (Dib et al., 2017), antimicrobial (Calo, Crandall, O'Bryan, & Ricke, 2015;Swamy, Akhtar, & Sinniah, 2016), antioxidant (Khodaei, Nguyen, Mdimagh, Bayen, & Karboune, 2021; Valdivieso-Ugarte, Gomez-Llorente, Plaza-Díaz, & Gil, 2019), anti-inflammatory (Pérez, Zavala, Arias, & Ramos, 2011;Zuo et al., 2020), immunomodulatory properties (Gandhi et al., 2020;Sandner, Heckmann, & Weghuber, 2020), insecticidal (Marques, Rocha, de Almeida, & Mota, 2021; Soares de Oliveira, Melo Coutinho, Jardelino de Lacerda Neto, Castro de Oliveira, & Bezerra da Cunha, 2020) and herbicidal effects (Travlos et al., 2020;Tworkoski, 2002). ...
Article
Essential oils (EOs) contain different types of chemical compounds such as alkaloids, isoflavones, flavonoids, monoterpenes, carotenoids, phenolic acids, and aldehydes with biological properties. However, when exposed to harsh environmental conditions, these compounds can become chemically unstable and susceptible to degradation, volatilization, and oxidation. Encapsulation technology has been largely employed to maintain the biological activities of EOs during the processing and development of novelty-enriched food products for industrial application. In this review, a brief description of EOs is presented and the main encapsulation methods used to protect them are highlighted. In addition, the structural characteristics and stability of encapsulated EOs were evaluated based on the rheological behavior, such as flow behavior, viscosity, and viscoelastic properties determined by two types of tests: oscillatory dynamic measurements (e.g., strain/stress sweep, time, temperature, and frequency sweep, including determination of storage modulus (G′), loss modulus (G″), complex modulus (G*), and complex viscosity (η*)), and static tests (creep and recovery). This work also contains information about fundamentals, principles, and importance of rheology for the evaluation of stability, strength, and structural characteristics of encapsulated EOs before the drying process to obtain nano(micro)particles. The knowledge of rheological behavior revealed to be important for large-scale industrial production, and application of encapsulated EOs, since during the processing and production, food products are submitted to high stress, temperature, and long-time operations.
... Researches show that the levels of IL-17, IL-1b, TNF-a, IL-6, and IL-4 significantly increase in COVID-19 patients compared with non-COVID-19 patients or healthy people, and IL-17, IL-1, and TNF have great dependence on Th17 adaptive immune response triggering the inflammation cascades in COVID-19 (26,94,97,98). Asthma is characterized by chronic inflammatory infiltration caused by inflammatory cells and immune cells, and inhibition of TNF-a, IL-1b, IL-17, IL-4, and IL-6 contributes to improving asthma (99). Furthermore, biomarkers of MAPK family members and JAK/ STAT signaling pathways show a significant upward trend in asthma patients (100). ...
Article
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Asthma patients may increase their susceptibility to SARS-CoV-2 infection and the poor prognosis of coronavirus disease 2019 (COVID-19). However, anti-COVID-19/asthma comorbidity approaches are restricted on condition. Existing evidence indicates that luteolin has antiviral, anti-inflammatory, and immune regulation capabilities. We aimed to evaluate the possibility of luteolin evolving into an ideal drug and explore the underlying molecular mechanisms of luteolin against COVID-19/asthma comorbidity. We used system pharmacology and bioinformatics analysis to assess the physicochemical properties and biological activities of luteolin and further analyze the binding activities, targets, biological functions, and mechanisms of luteolin against COVID-19/asthma comorbidity. We found that luteolin may exert ideal physicochemical properties and bioactivity, and molecular docking analysis confirmed that luteolin performed effective binding activities in COVID-19/asthma comorbidity. Furthermore, a protein–protein interaction network of 538 common targets between drug and disease was constructed and 264 hub targets were obtained. Then, the top 6 hub targets of luteolin against COVID-19/asthma comorbidity were identified, namely, TP53, AKT1, ALB, IL-6, TNF, and VEGFA. Furthermore, the enrichment analysis suggested that luteolin may exert effects on virus defense, regulation of inflammation, cell growth and cell replication, and immune responses, reducing oxidative stress and regulating blood circulation through the Toll-like receptor; MAPK, TNF, AGE/RAGE, EGFR, ErbB, HIF-1, and PI3K–AKT signaling pathways; PD-L1 expression; and PD-1 checkpoint pathway in cancer. The possible “dangerous liaison” between COVID-19 and asthma is still a potential threat to world health. This research is the first to explore whether luteolin could evolve into a drug candidate for COVID-19/asthma comorbidity. This study indicated that luteolin with superior drug likeness and bioactivity has great potential to be used for treating COVID-19/asthma comorbidity, but the predicted results still need to be rigorously verified by experiments.
... The structure and concentration of essential oils (EOs) determine their therapeutic effects. As a result, a broad range of bioactive properties can be seen, as well as neuroprotective, hepatoprotective, cardioprotective, antioxidant, anxiolytic, anti-cancer, anti-bacterial, antiinflammatory, anti-diabetic, antiviral, anti-hyperpigmentation, antibiotic, and acaricidal Figure 2 [11,[36][37][38]. ...
Article
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Essential oils (EOs) are complex mixtures of volatile compounds with different biological properties. Essential oils and their ability to resist the production of biofilms by pathogenic microorganisms have been linked to antimicrobial activity. After adherence of these pathogenic microorganisms to surfaces leads primarily to antibiotic resistance, it is vital to look for compounds or methodologies with this capacity. Essential oils have gained a lot of attention in recent years due to studies of their anti-bacterial, antiviral, anti-fungal, and insecticidal properties. Due to their low toxicity, biocompatibility, biodegradability, capability to precisely target tissue, and initial structures that enable various therapeutics to be attached, MNPs (magnetite nanoparticles) are one kind of nanocarrier that could be used to deliver EOs for antimicrobial therapies effectively.
... Aromatherapy has been explicitly and/or implicitly part of CIM worldwide, particularly in the field of botanical medicine, where such properties are used to achieve specific therapeutic goals (118)(119)(120), for example to reduce anxiety (121). Due to their anti-microbial portfolio, several of these substances are of interest for the prevention of (respiratory) infections, the supportive treatment of conventional treatments, or a stand-alone CIM therapy in the case of a mild course of respiratory tract infections (122). ...
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Background: During the COVID-19 pandemic people are facing risks of adverse health effects due to the restrictions implemented such as quarantine measures, reduced social contact, and self-isolation. In this qualitative review, we collected data on potential preventive and therapeutic health benefits of Complementary and Integrative Medicine (CIM) that might be useful during the COVID-19 pandemic. We have reviewed the scientific literature to summarize CIM practices that could be beneficial for improving physical and mental health and well-being of the population under the current pandemic circumstances. It must be noted that this review is not SARS-CoV-2 specific and we explicitly do not intend to make any SARS-CoV-2 specific health claims in this article. Methods and Findings: A qualitative, non-systematic literature review was conducted in Medline to identify literature describing preventive and therapeutic CIM approaches for strengthening mental and physical health. For a variety of CIM approaches clinical evidence was identified, indicating beneficial effects. CIM approaches include specific dietary measures and selected micronutrients, physical activity, techniques from Mind-Body Medicine, single botanicals or botanical compounds, and spending time in nature among others. The effects of CIM measures on conditions like obesity and hypertension are of special relevance here, as these conditions are considered as risk factors for a severe course of COVID-19. Moreover, a possibly direct effect of CIM approaches on immune functions and clinical parameters in respiratory tract infections, such as influenza, were identified. The findings of this review could be helpful for clinicians, patients, and the general population during the current pandemic when discussing and/or considering CIM options. Conclusions: CIM offers a variety of preventive and therapeutic options for strengthening physical and mental resilience, which could also be useful in the current COVID-19 pandemic. The evidence of CIM approaches with a potential benefit in the COVID-19 pandemic in different areas is worth to be analyzed. While this qualitative review has several obvious limitations, it might serve as useful starting point for further research on this topic.
... Traditionally, ginger and ginger volatile oils, curcumin, Panax L. (Araliaceae) and garlic are recommended and used to strengthen immunity and reduce the likelihood of inflammatory respiratory diseases [2,17,18]. In an in vitro study [19], Allium sativum L. (Amaryllidaceae) extract inhibited influenza A (H 1 N 1 ) virus by inhibiting the synthesis of viral nucleoproteins and polymerase activity. ...
Article
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The development of new effective anti-coronavirus drugs and therapies is important, but it requires significant human, financial and, most importantly, time expenditures. The current pandemic is neither the first nor the last. Humanity has already accumulated considerable survival experience. We cannot do without prevention and epidemiological protection measures. This study reviews medicinal plants that grow in Northeast Asia and whose antioxidant, antiviral, anti-inflammatory and immunomodulatory characteristics are already known, also in the framework of the prevention and treatment of pneumonia of various etiologies. The need for a comprehensive approach to maintaining immunodefences, including functional foods and positive emotions, is emphasized. In the period of pandemics, it is important to research various areas that allow to us accumulate a critical mass of information and cope with the next global disease.
... Allergic asthma represents a worldwide public health problem affecting more than 350 million people worldwide [1,2]. This is a chronic inflammatory disease of the lower airways, characterized by overproduction of mucus, airway hyperresponsiveness, tissue remodeling and recruitment of inflammatory cells, with a predominance of eosinophilic inflammation [3]. Symptoms vary over time in terms of occurrence, frequency and intensity and generally include chest tightness, wheezing, coughing, shortness of breath and reduced lung function [4]. ...
... Another factor associated with the development of NP is the increasement of TNF-α, IL-1β and IL-6 levels in the dorsal root and spinal cord ganglia (Chen et al., 2018;Wei et al., 2012;Zang et al., 2015). Natural products are strong pro-inflammatory cytokine modulators (Quintans et al., 2019;Gandhi et al., 2020). Study performed by Huang et al. (2010) showed that the suppression of NF-κB activation by quercetin in LPS-stimulated dendritic cells is related to the inhibition of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6). ...
Article
Medicinal plants remain an invaluable source for therapeutics of diseases that affect humanity. Sideritis bilgeriana (Lamiaceae) is medicinal plant used in Turkey folk medicine to reduce inflammation and pain, but few studies scientific corroborates its medicinal use so creating a gap between popular use and scientific evidence. Thus, we aimed to evaluate the pharmacological effects of the methanolic extract of S. bilgeriana (MESB) in rodents nociception models and also performed its phytochemical analysis. Firstly, a screening was carried out that enabled the identification of the presence of phenolic compounds and flavonoids. In view of this, a chromatographic method by HPLC-DAD-UV was developed that made it possible to identify chlorogenic acid and its quantification in MESB. MESB-treated mice (MESB 50, 100 and 200 mg/kg, p.o.) reduced mechanical hyperalgesia and myeloperoxidase activity (p<0.01), and also showed a reduced pain behavior in capsaicin test. In the carrageenan-induced pleurisy test, MESB (100 mg/kg p.o.) significantly reduced the leukocyte (polymorphonuclear) count in the pleural cavity and equally decreased the TNF-α and IL-1β levels (p<0.001). In the PSNL model, mechanical hyperalgesia was reduced on the first evaluation day and during the 7 days of evaluation compared to the vehicle group (p<0.001). Thermal hyperalgesia was also reduced 1 hour after treatment compared to the vehicle group (p<0.001) and reversed the loss of force initially displayed by the animals, thus inferring an analgesic effect in the muscle strength test. Analysis of the marrow of these animals showed a decrease in the level of pro-inflammatory cytokine IL-6 (p<0.001) and factor NF-κB, in relation to the control group (p <0.05). Moreover, the MESB treatment produced no noticeable side effects, no disturb in motor performance and no signs of gastric or hepatic injury. Together, the results suggests that MESB could be useful to management of inflammation and neuropathic pain mainly by the management of pro-inflammatory mediators (NF-κB, TNF-α, IL-1β and IL-6), so reinforcing its use in popular medicine and corroborating the need for further chemical and pharmacological studies for the species..
... The essential oils or their constituents can act as immune-modulating of the inflammatory process under macrophages, natural killer cells (NK) and T and B lymphocytes, production of cytokines, chemokines and interleukins, among other mechanisms, becoming potential sources of new compounds treatments for regulation of persistent stimuli that can lead to autoimmune diseases, allergies, arthritis, cancers and atherosclerosis (Gandhi et al., 2019;Anastasiou and Buchbauer, 2017;Han et al., 2017). ...
Article
Ethnopharmacological relevance Verbesina macrophylla (Cass.) S.F.Blake is a medicinal plant from South America, popularly known as "asa de peixe", "asa de peixe branco", "cambará branco" or "cambará guaçu", being used by traditional communities for its healing powers in the form of teas, infusions, liqueurs and extracts, for the treatment of bacterial and fungal infections of the urinary and respiratory tracts, such as kidney problems, bronchitis, inflammation and fever. However, none of the ethnopharmacological properties has been scientifically evaluated. Aim of the study Based on the ethnopharmacological use of the species, this study investigated the chemical composition, and for the first time acute toxicity, hemolytic, antimicrobial, anti-inflammatory and antipyretic activities of the essential oil from leaves of V. macrophylla (EOVm). Material and methods The EOVm were obtained from the leaves by hydrodistillation (HD), being characterized by gas chromatography coupled to mass spectrometry (GC-MS) and gas chromatography coupled to flame ionization detection (GC-FID). The antimicrobial activity was evaluated by the broth microdilution technique in bacteria and fungi that cause infections of the respiratory and urinary tract, and toxicological safety regarding hemolytic activity on human red blood cells (hRBCs), and acute toxicity in mice. The anti-inflammatory activity was evaluated by the model carrageenan-induced peritonitis with quantification of the levels of TNF-α and IL-1β in the intraperitoneal fluid, and ear edema induced by croton oil. The antipyretic activity evaluated in mice with pyrexia induced by yeast. Results The extraction of EOVm by hydrodistillation (HD) showed a yield of 0.33 ± 0.04%, with its composition constituted mainly by sesquiterpenes of hydrocarbons (94.00%). The essential oil demonstrated antibacterial and antifungal activity, with a low rate of hemolysis in human red blood cells (hRBCs) and no clinical signs of toxicity were observed in animals after acute treatment, which suggested that the LD50 is greater than 5,000 mg/kg; p.o. The EOVm demonstrated anti-inflammatory activity reducing levels of pro-inflammatory cytokines TNF-α (38.83, 72.42 and 73.52%) and IL-1β (37.70, 75.92 and 87.71%), and ear edema by 49.53, 85.04 and 94.39% at concentrations of 4, 40 and 400 mg/kg, respectively. The antipyretic activity presented by the EOVm is statistically similar to dipyrone. Conclusion The set of results obtained, validates the main activities attributed to the traditional use of Verbesina macrophylla (Cass.) S.F.Blake. These data add industrial value to the species, considering that the antimicrobial, anti-inflammatory and antipyretic activities present results similar to the drugs already used also presenting safety. The results suggest that EOVm may be used by industry for the development of drugs with natural antimicrobial, anti-inflammatory and antipyretic effect.
... Currently, many studies have hypothesized that the olfactory system influences the immune system 48 . Accordingly, essential oils are also used in aromatherapy given their antimicrobial, anti-inflammatory, and immune system-enhancing properties [49][50][51] . Garlic is one agent that boosts the functioning of the immune system in such a way 44 . ...
Article
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Background Pandemics of infectious diseases have long been regarded as societal challenges. This study aimed to summarize the theories of Persian medicine for controlling respiratory disease-related pandemics and to compare these theories with the findings of modern medicine. Methods We searched the classic medical reference books of the 9th to 19th centuries for the terms ‘polluted air’ and ‘pandemic’, and we searched 4 databases (PubMed, Google Scholar, Science Direct, and Scopus) with the keywords ‘COVID-19’, ‘pandemic’, ‘history’, and ‘prevention programs’. The results were collected and subjected to content analysis. Results From the point of view of traditional Iranian physicians, disease prevention is primarily possible by avoiding pathogenic factors. As a secondary solution, reducing one's susceptibility to the disease is crucial; this can be achieved through cleansing the body and strengthening the mood, reducing food intake, decreasing the internal humidity, disinfecting the house with herbal fumigation, and making use of pleasant aromas. Some of these recommendations are reaffirmed by modern research. Conclusion Persian medicine techniques may be preventive during respiratory, influenza-like disease pandemics. However, rigorous studies are needed to confirm this hypothesis.
... Another factor associated with the development of NP is the increasement of TNF-α, IL-1β and IL-6 levels in the dorsal root and spinal cord ganglia (Chen et al., 2018;Wei et al., 2012;Zang et al., 2015). Natural products are strong pro-inflammatory cytokine modulators (Quintans et al., 2019;Gandhi et al., 2020). Study performed by Huang et al. (2010) showed that the suppression of NF-κB activation by quercetin in LPS-stimulated dendritic cells is related to the inhibition of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6). ...
Article
Ethnopharmacological relevance: Miconia albicans (Sw) Triana (Melastomataceae), a medicinal plant widely used by practitioners of folk medicine in the northeast of Brazil, has been used to treat chronic inflammatory disorders, such as rheumatoid arthritis (RA) and other joint conditions. Oddly, there is little research on the species. Aim of the study: We aimed to evaluate the anti-arthritic and anti-inflammatory profile of the ethanolic leaf extract of M. albicans (EEMA), as well as to perform dereplication and quantification by HPLC-DAD-ESI-/MS/MS. Materials and methods: The compounds present in the extracts were identified by HPLC-DAD-ESI-MS/MS. The possible anti-inflammatory effect of EEMA (50 and 100mg/kg, p.o) was evaluated using the pleurisy model induced by carrageenan and its action on IL-1β and TNF-α levels was also evaluated. The RA model was induced through the intra-articular injection of complete Freund's adjuvant (CFA). Results: HPLC-DAD-ESI-MS/MS analysis identified 23 compounds, with glycoside flavonoids mainly derived from quercetin, and rutin being the main compounds. EEMA significantly reduced (p< 0.001) leukocyte migration in the pleurisy model and reduced TNF-α and IL-1β levels in pleural lavage (p<0.001). In the CFA animal model, EEMA significantly reduced the nociceptive and hyperalgesic behaviors demonstrated by the rearing test (p<0.01 or p<0.05) and decreased mechanical hyperalgesia (p<0.001). EEMA produced a significant improvement in mobility in the open-field test (only at the higher dose, p <0.05). EEMA significantly (p<0.01) increased hindpaw grip strength. The diameter of CFA-induced ipsilateral knee edema was significantly reduced (p<0.001) by EEMA, which was related to reduced levels of IL-6 and TNF-α in the joint knee (p<0.01). No indication of hepatic injury after chronic treatment was found. Conclusion: Taken together, these results contribute to the chemical and pharmacological knowledge of M. albicans and demonstrated that this medicinal plant appears to be able to mitigate deleterious symptoms of RA, which supports its use in folk medicine.
... These oils exert antifungal, antibacterial, gastroprotective, anticancer and many other therapeutically effects. 1 Several studies have focused on the benefits of these phytochemicals and their effect on human health. For example, the minimum inhibitory concentration of oregano essential oil against multiple drug-resistant Escherichia coli was 0.5μl ml -1 . ...
... The anti-inflammatory and immune-modulating activities of essential oils and their bioactive compounds was also linked to cytokine expression showing their potential therapeutic activity for the treatment of asthma. [361] Specifically, for our five essential oils, the anti-inflammatory activity has been recently reported for oregano essential oil on lipopolysaccharide (LPS)-treated murine macrophage cells. Oregano EO protects against the LPS-induced cell inflammatory response through the NADPH oxidase/ROS pathway. ...
Article
Lamiaceae is one of the largest families of flowering plants comprising about 250 genera and over 7,000 species. The majority of the plants of this family are aromatic and therefore important source of essential oils. Lamiaceae are widely used as culinary herbs and reported as medicinal plants in several folk traditions. In the Mediterranean area oregano, sage, rosemary, thyme and lavender stand out for geographical diffusion and variety of uses. The aim of this review is to provide recent data dealing with the phytochemical and pharmacological studies, and the more recent applications of the essential oils and the non‐volatile phytocomplexes. This literature survey suggests how the deeper understanding of biomolecular processes in the health and food sectors as per as pest control bioremediation of cultural heritage, or interaction with human microbiome, fields, leads to the rediscovery and new potential applications of well‐known plants.
... Aromatherapy is a field of complementary medicine that uses EOs to treat and prevent diseases via several routes of administration: Usually topical, massage, inhalation, or oral [13]. Antimicrobial, anti-inflammatory, antioxidant, anticancer, anxiolytic, antidepressant, analgesic, and antidiabetic activities of EOs have been studied and reported recently [14][15][16][17][18][19][20]. Scientific evidence on the immunostimulatory effects of EOs is rather fragmentary, but there seems to be a potential for certain EOs to be able to enhance some immune functions. ...
Article
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The augmenting acceptance and application of herbal medicine in prevention and treatment of diseases also involve the use of plant essential oils (EOs) through different routes of administration (aromatherapy). Scientific data supporting the efficacy of certain herbal products are continuously growing; however, the cumulative evidence is not always sufficient. The anti-inflammatory properties of EOs have been investigated more extensively and also reviewed in different settings, but so far, our review is the first to summarize the immune-supporting properties of EOs. Our aim here is to synthesize the currently available data on the immune function enhancing effects of EOs. An online search was conducted in the PubMed database, which was terminated at the end of July 2019. Other articles were found in the reference lists of the preselected papers. Studies that applied whole EOs with known components, or single EO constituents under in vitro or in vivo laboratory conditions, or in human studies, and de facto measured parameters related to immune function as outcome measures were included. Two specific fields, EO dietary supplementation for livestock and fish, and forest bathing are also explored. Some EOs, particularly eucalyptus and ginger, seem to have immune function enhancing properties in multiple studies.
... Essential oils (EOs) are usually extracted from plants and are used for aromatherapy, which is an alternative medicine that demonstrates the healing effect to the aromatic compounds presented in the oil [1,2]. Although its therapeutic potential remains controversial, the usage of essential oil has been increasingly popular in the general population [3]. ...
Article
Essential oils have been advertised endlessly to be very beneficial for the health of humans, and an extensive amount of research examines the validity of such claims. In contribution, the current study evaluates the neuroprotective properties of Citronellol and Geraniol essential oils (EOs). In relationship to the biophysical gating properties of different the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunits, the EOs were administered to HEK293 (Human embryonic kidney 293) cells and examined for any inhibition and effect on desensitization or deactivation rates, using whole-cell patch-clamp electrophysiology. Our results demonstrated the highest levels of inhibition from Citronellol oil by four-fold on all AMPARs subunits. Likewise, Geraniol oil had a similar inhibiting impact on the receptors, and both oils decreased the desensitization and deactivation rates of the inhibited receptors. Thus, the examined EOs of this study portray neuroprotective qualities by targeting AMPARs activation and reducing desensitization and deactivation rates. Finally, the results of the current study entail a better understanding of AMPARs, provides a natural template for future drug synthesis to treat neurological diseases associated with excessive AMPAR activation, and offers a possible mechanism by which these essential oils deploy their ‘calming’ effect.
... Uncited references [97] ...
Article
Neuropathic pain (NP) is a difficult condition to treat because of the modest efficacy of available drugs. New treatments are required. In the study we aimed to investigate the effects of the essential oil from Lippia grata alone or complexed in β-cyclodextrin (LG or LG-βCD) on persistent inflammatory and neuropathic pain in a mouse model. We also investigated Ca2+ currents in rat dorsal root ganglion (DRG) neurons. Male Swiss mice were treated with LG or LG/β-CD (24 mg/kg, i.g.) and their effect was evaluated using an acute inflammatory pleurisy model and nociception triggered by intraplantar injection of an agonist of the TRPs channels. We also tested their effect in chronic pain models: injection of Freund's Complete Adjuvant and partial sciatic nerve ligation (PSNL). In the pleurisy model, LG reduced the number of leukocytes and the levels of TNF-α and IL-1β. It also inhibited cinnamaldehyde and menthol-induced nociceptive behavior. The pain threshold in mechanical and thermal hyperalgesia was increased and paw edema was decreased in models of inflammatory and neuropathic pain. PSNL increased inflammatory protein contents and LG and LG-βCD restored the protein contents of TNF-α, NF-κB, and PKA, but not IL-1β and IL-10. LG inhibited voltage gated Ca2+ channels from DRG neurons. Our results suggested that LG or LG-βCD produce anti-hyperalgesic effect in chronic pain models through reductions in TNF-α levels and PKA, and inhibited voltage-gated calcium channels and may be innovative therapeutic agents for the management of NP.
Article
The essential oil of Citrus sudachi (sudachi oil) is extracted from the peel of sudachi, a citrus plant. We investigated the effect of sudachi oil on immune function in both in vitro antigen (Ag) induced lymphocyte activation and in vivo Ag-specific immune response. In the in vitro study, the proliferative activity of splenocytes upon Ag-specific and non-specific stimulation was suppressed by treatment with sudachi oil in a dose-dependent manner. In addition, the expression level of Ag-presentation-related molecules and their Ag-presenting function on dendritic cells were suppressed by sudachi oil. To examine how sudachi oil regulates an Ag-specific immune response in vivo, mice were immunized with ovalbumin and the immune response of the mice was investigated. Ag-specific proliferation response of splenocytes from mice treated with sudachi essential oil was significantly suppressed. The results indicate that sudachi oil suppresses T cell and dendritic cell functions in vitro and Ag-specific T cell induction in vivo.
Article
Ethnopharmacological relevance: Essential oils (EOs) are concentrated hydrophobic liquids with volatility and a unique aroma. Formed by aromatic plants as secondary metabolites, EOs have been used as traditional medicines to treat various health problems worldwide. Historical records show that herbs rich in EOs have been widely used to treat respiratory diseases in China, Europe, and many other regions. Aim of the review: This review summarizes the traditional applications and modern pharmacological mechanisms of EOs derived from aromatic herbs and their active ingredients in respiratory diseases in preclinical and clinical trials through multitarget synergy. Materials and methods: Information about EOs and respiratory diseases was collected from electronic databases, such as ScienceDirect, Web of Science, PubMed, Google Scholar, Baidu Scholar, and the China National Knowledge Infrastructure (CNKI). Results: This review presents the preventive and therapeutic effects of EOs on respiratory diseases, including chronic obstructive pulmonary disease, bronchial asthma, acute lung injury, pulmonary infection, and pulmonary fibrosis. The molecular mechanisms of EOs in treating different lung diseases are summarized, including anti-inflammation, anti-oxidation, mucolytic, and immune regulatory mechanisms. Conclusions: EOs show potential as supplements or substitutes for treating lung diseases.
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Propolis is a resinous mixture of substances collected and processed from various botanical sources by honeybees. Black poplar (Populus balsamifera L.) buds are one of the primary sources of propolis. Despite their reported therapeutic properties, little is known about the innate immunomodulatory activity of essential oils from P. balsamifera and propolis. In the present studies, essential oils were isolated from the buds of P. balsamifera and propolis collected in Montana. The main components of the essential oil from P. balsamifera were E-nerolidol (64.0%), 1,8-cineole (10.8%), benzyl benzoate (3.7%), α-terpinyl acetate (2.7%), α-pinene (1.8%), o-methyl anisol (1.8%), salicylaldehyde (1.8%), and benzyl salicylate (1.6%). Likewise, the essential oil from propolis was enriched with E-nerolidol (14.4%), cabreuva oxide-VI (7.9%), α-bisabolol (7.1%), benzyl benzoate (6.1%), β-eudesmol (3.6%), T-cadinol (3.1%), 2-methyl-3-buten-2-ol (3.1%), α-eudesmol (3.0%), fokienol (2.2%), nerolidol oxide derivative (1.9%), decanal (1.8%), 3-butenyl benzene (1.5%), 1,4-dihydronaphthalene (1.5%), selina-4,11-diene (1.5%), α-cadinol (1.5%), linalool (1.4%), γ-cadinene (1.4%), 2-phenylethyl-2-methyl butyrate (1.4%), 2-methyl-2-butenol (1.3%), octanal (1.1%), benzylacetone (1.1%), and eremoligenol (1.1%). A comparison between P. balsamifera and propolis essential oils demonstrated that 22 compounds were found in both essential oil samples. Both were enriched in E-nerolidol and its derivatives, including cabreuva oxide VI and nerolidol oxides. P. balsamifera and propolis essential oils and pure nerolidol activated Ca2+ influx in human neutrophils. Since these treatments activated neutrophils, the essential oil samples were also evaluated for their ability to down-regulate the neutrophil responses to subsequent agonist activation. Indeed, treatment with P. balsamifera and propolis essential oils inhibited subsequent activation of these cells by the N-formyl peptide receptor 1 (FPR1) agonist fMLF and the FPR2 agonist WKYMVM. Likewise, nerolidol inhibited human neutrophil activation induced by fMLF (IC50 = 4.0 μM) and WKYMVM (IC50 = 3.7 μM). Pretreatment with the essential oils and nerolidol also inhibited human neutrophil chemotaxis induced by fMLF, again suggesting that these treatments down-regulated human neutrophil responses to inflammatory chemoattractants. Finally, reverse pharmacophore mapping predicted several potential kinase targets for nerolidol. Thus, our studies have identified nerolidol as a potential anti-inflammatory modulator of human neutrophils.
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In the present study, Monarda didyma L. essential oil (isolated from the flowering aerial parts of the plant) was examined to characterize its chemotype and to evaluate, in addition to the quali-quantitative chemical analysis, the associated antioxidant and anti-inflammatory activities. The plants were grown in central Italy, Urbino (PU), Marche region. Different analyses (TLC, GC-FID, GC-MS and ¹ H-NMR) allowed the identification of twenty compounds among which carvacrol, p-cymene and thymol were the most abundant. On this basis, the chemotype examined in the present study was indicated as Monarda didyma ct. carvacrol. The antioxidant effect was assessed by DPPH assay. Moreover, this chemotype was investigated for the anti-inflammatory effect in an in vitro setting ( i.e ., LPS-stimulated U937 cells). The decreased expression of pro-inflammatory cytokine IL-6 and the increased expression of miR-146a are suggestive of the involvement of the Toll-like receptor-4 signaling pathway. Although further studies are needed to better investigate the action mechanism/s underlying the results observed in the experimental setting, our findings show that M. didyma essential oil is rich in bioactive compounds (mainly aromatic monoterpenes and phenolic monoterpenes) which are most likely responsible for its beneficial effect.
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Grindelia squarrosa (Pursh) Dunal is used in traditional medicine for treating various diseases; however, little is known about the immunomodulatory activity of essential oils from this plant. Thus, we isolated essential oils from the flowers (GEOFl) and leaves (GEOLv) of G. squarrosa and evaluated the chemical composition and innate immunomodulatory activity of these essential oils. Compositional analysis of these essential oils revealed that the main components were α-pinene (24.7 and 23.2% in GEOFl and GEOLv, respectively), limonene (10.0 and 14.7%), borneol (23.4 and 16.6%), p-cymen-8-ol (6.1 and 5.8%), β-pinene (4.0 and 3.8%), bornyl acetate (3.0 and 5.1%), trans-pinocarveol (4.2 and 3.7%), spathulenol (3.0 and 2.0%), myrtenol (2.5 and 1.7%), and terpinolene (1.7 and 2.0%). Enantiomer analysis showed that α-pinene, β-pinene, and borneol were present primarily as (−)-enantiomers (100% enantiomeric excess (ee) for (−)-α-pinene and (−)-borneol in both GEOFl and GEOLv; 82 and 78% ee for (−)-β-pinene in GEOFl and GEOLv), while limonene was present primarily as the (+)-enantiomer (94 and 96 ee in GEOFl and GEOLv). Grindelia essential oils activated human neutrophils, resulting in increased [Ca2+]i (EC50 = 22.3 µg/mL for GEOFl and 19.4 µg/mL for GEOLv). In addition, one of the major enantiomeric components, (−)-borneol, activated human neutrophil [Ca2+]i (EC50 = 28.7 ± 2.6), whereas (+)-borneol was inactive. Since these treatments activated neutrophils, we also evaluated if they were able to down-regulate neutrophil responses to subsequent agonist activation and found that treatment with Grindelia essential oils inhibited activation of these cells by the N-formyl peptide receptor 1 (FPR1) agonist fMLF and the FPR2 agonist WKYMVM. Likewise, (−)-borneol inhibited FPR-agonist-induced Ca2+ influx in neutrophils. Grindelia leaf and flower essential oils, as well as (−)-borneol, also inhibited fMLF-induced chemotaxis of human neutrophils (IC50 = 4.1 ± 0.8 µg/mL, 5.0 ± 1.6 µg/mL, and 5.8 ± 1.4 µM, respectively). Thus, we identified (−)-borneol as a novel modulator of human neutrophil function.
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Mast cells (MCs) are hematopoietic immune cells commonly found in adjacent to blood vessels in the lamina propria of airway mucosa. They are important in allergic reactions since the cross-linking of their surface high affinity receptor FceRI induces activation of these cells, and provokes the synthesis, degranulation and release of inflammatory mediators including arachidonic acid-derived eicosanoids (de novo synthesized), stored enzyme mediators, and inflammatory TH1 and TH2 cytokines, and chemokines. Interleukin (IL)-33 participates in innate and adaptive immunity and inflammation and, acting on CD34+ cells, causes MC differentiation and maturation. IL-33 is generated by activated immune cells, and activates MCs which degranulate and release pro-inflammatory mediators. IL-33 is very important in mediating allergic inflammation and can be induced by IL-1 beta. It is also called “alarmin” and is an inflammatory cytokine IL-1 family member, expressed from mocytes and MCs, which binds its receptor ST2, provoking its release after cell damage. MC-derived allergic compounds in response to IL-33 is critical to innate type 2 immunity. IL-37 is expressed by immune and non-immune cells after pro-inflammatory stimulus. IL-37, an anti-inflammatory cytokine, binds IL-18Ra and suppresses pro-inflammatory IL-1 beta released by activated immune cells such as macrophages. Here, we hypothesize that pro-inflammatory IL-1 family member cytokines released by activated MCs, mediating inflammatory allergic phenomenon, can be suppressed by IL-37.
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Objective This study summarized asthma literature indexed in the Medical Literature Analysis and Retrieval System Online (MEDLINE) and explored the history and present trends of asthma cell research by stem frequency ranking to forecast the prospect of future work. Methods Literature was obtained from MEDLINE for the past 30 years and divided into three groups by decade as the retrieval time. The frequency of stemmed words in each group was calculated using Python with Apache Spark and the Natural Language Tool Kit for ranking. The unique stems or shared stems of 3 decades were summarized. Results A total of 1331, 4393, and 7215 records were retrieved from 3 decades chronologically, and the stem ranking of the top 50 were listed by frequency. The number of stems shared with 3 decades was 26 and with the first and last 2 decades was 5 and 13. Conclusions The number of cell research studies of asthma has increased rapidly, and scholars have paid more attentions on experimental research, especially on mechanistic research. Eosinophils, mast cells, and T cells are the hot spots of immunocyte research, while epithelia and smooth muscle cells are the hot spots of structural cell research. The research trend is closely linked with the development of experimental technology, including animal models. Early studies featured basic research, but immunity research has dominated in recent decades. The distinct definition of asthma phenotypes associated with genetic characteristics, immunity research, and the introduction of new cells will be the hot spots in future work.
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Background/aims: Thymic stromal lymphopoietin (TSLP) is a cytokine that plays diverse roles in the regulation of immune responses. However, a detailed understanding of the TSLP signaling pathway in asthma remains elusive. In this study, we aimed to investigate the role of the TSLP signaling pathway in asthma and its effect on airway inflammation and remodeling. Methods: Forty Sprague Dawley (SD) rats were evenly classified into control, asthma, IgG2a mAb and anti-TSLP mAb groups. Ovalbumin (OVA)-induced asthma models were successfully established. Blood, bronchoalveolar lavage fluid (BALF) and lung tissue samples were prepared. Total BALF leukocytes were counted, and the proportions of different leukocyte types were determined. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry were performed to determine the mRNA and protein levels of TSLP, OX40L, α-smooth muscle actin (α-SMA, a marker of airway remodeling in asthma) and collagen I in the plasma. Enzyme-linked immunosorbent assay (ELISA) was carried out to measure the concentrations of TSLP, OX40L, and other inflammatory factors, such as interferon (IFN)-γ, interleukin (IL)-4, IL-5 and IL-13, in the plasma. Results: Compared with the control group, there were more leukocytes, increased EOS and LYM proportions, higher Underwood and PAS scores, increased WTt, WTm, WAt/A0, WAm/WAt, WTt/R0, WTm/WTt, TSLP, OX40L, a-SMA and collagen I mRNA and protein levels, and higher SLP, OX40L, IL-4, IL-5 and IL-13 levels, but lower MON proportions and IFN-γ levels in the asthma and IgG2a mAb groups. Compared with the asthma and IgG2a mAb groups, there were less leukocytes, decreased EOS and LYM proportions, lower Underwood and PAS scores, decreased WTt, WTm, WAt/A0, WAm/WAt, WTt/R0, WTm/WTt, TSLP, OX40L, a-SMA and Collagen I mRNA and protein levels, and lower levels of SLP, OX40L, IL-4, IL-5 and IL-13, but higher MON proportions and IFN-γ levels in the anti-TSLP mAb group. WTm and WTt were positively associated with the TSLP, OX40L, α-SMA and collagen-I levels in the rat lung tissues. Conclusion: The results indicate that TSLP may be an important contributor for asthma development as TSLP signaling blockade attenuates airway inflammation and remodeling in asthmatic rats.
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Objective The preventive effect of Zataria multiflora in animal models of asthma has been reported. In the present study, its effect on wheezing, forced expiratory volume in 1 second, and plasma nitrite (NO²⁻) in asthmatic patients was studied. Materials and Methods In this study, forty asthmatic patients including 15 males and 25 females (aged 45.8±6.21 years) were randomly allocated in four groups including placebo group (P), and three treatment groups which received two doses of Z. multiflora (groups Z low and Z high that received 5 and 10 mg/kg/day, respectively) and carvacrol (group C treated with 1.2 mg/kg/day). All patients were treated for two months in a double-blind manner. At three time points (before starting the treatment (pretreatment), and one and two month after treatment), wheezing during day and exercise, forced expiratory volume in 1 second and NO²⁻ were measured. Results Day wheeze and exercise wheeze were significantly reduced in treated groups with carvacrol and both doses of Z. multiflora compared to pretreatment (p<0.05 to p<0.01). However, FEV1% was significantly increased in treated groups with carvacrol and both doses of Z. multiflora (p<0.05 to p<0.001). Plasma level of NO²⁻ was also significantly decreased in Z high and carvacrol groups after two months of treatment (p<0.01 to p<0.001). However, most of evaluated parameters in placebo group did not show significant changes during the study. Conclusion Z. multiflora and its constituent, carvacrol, improved FEV1% while reduced wheezing and plasma level of NO²⁻ in asthmatic patients. Therefore, a possible therapeutic potential for this plant and its constituent, carvacrol could be suggested to be used against asthma.
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The relaxant effects of carvacrol, a phenolic monoterpene, on tracheal smooth muscle and its preventive effect on asthmatic animals were reported. The effect of carvacrol in asthmatic patients was examined in the placebo group (Group P, n = 11) receiving placebo and treatment group (Group C, n = 12), which received carvacrol capsule (1.2 mg/kg/day) for 2 months in a double-blind manner. Pulmonary function tests, respiratory symptoms, hematological indices, and high-sensitivity C-reactive protein (hs-CRP) were measured before, 1 and 2 months after starting treatment. At the end of treatment period, Pulmonary function tests values in Group C were significantly increased (p < .05 to p < .001). Most respiratory symptoms were also significantly reduced in Group C at the end of 2-month treatment (p < .05 to p < .001). Total and differential white blood cell (p < .05 to p < .001), as well as serum levels of hs-CRP in Group C were also significantly reduced after 2-month treatment with carvacrol (p < .001). Mean corpuscular hemoglobin concentration and hematocrit were changed in Group C (p < .05 and p < .01, respectively). However, in Group P, there was no significant changes in the evaluated parameters. Pulmonary function tests were increased but respiratory symptoms, inflammatory cells, and hs-CRP were reduced in asthmatic patients who received carvacrol that indicates its therapeutic effect on asthma.
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Chitin is produced in large amounts by fungi, insects, and other organisms and has been implicated in the pathogenesis of asthma. Airway epithelial cells are in direct contact with environmental particles and serve as the first line of defense against inhaled allergens and pathogens. The potential contributions of airway epithelial cells to chitin-induced asthma remain poorly understood. We hypothesized that chitin directly stimulates airway epithelial cells to release cytokines that promote type 2 immune responses and to induce expression of molecules which are important in innate immune responses. We found that chitin exposure rapidly induced the expression of three key type 2-promoting cytokines, IL-25, IL-33 and TSLP, in BEAS-2B transformed human bronchial epithelial cells and in A549 and H292 lung carcinoma cells. Chitin also induced the expression of the key pattern recognition receptors TLR2 and TLR4. Chitin induced the expression of miR-155, miR-146a and miR-21, each of which is known to up-regulate the expression of pro-inflammatory cytokines. Also the expression of SOCS1 and SHIP1 which are known targets of miR-155 was repressed by chitin treatment. The monoterpene phenol carvacrol (Car) and its isomer thymol (Thy) are found in herbal essential oils and have been shown to inhibit allergic inflammation in asthma models. We found that Car/Thy inhibited the effects of chitin on type 2-promoting cytokine release and on the expression of TLRs, SOCS1, SHIP1, and miRNAs. Car/Thy could also efficiently reduce the protein levels of TLR4, inhibit the increase in TLR2 protein levels in chitin plus Car/Thy-treated cells and increase the protein levels of SHIP1 and SOCS1, which are negative regulators of TLR-mediated inflammatory responses. We conclude that direct effects of chitin on airway epithelial cells are likely to contribute to allergic airway diseases like asthma, and that Car/Thy directly inhibits epithelial cell pro-inflammatory responses to chitin.
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Background: In a murine model for house dust mite (HDM)-induced asthma, dietary galacto-oligosaccharides have been shown to suppress allergic symptoms. Previously, CD25(+) regulatory T cells (Tregs) induced by nondigestible oligosaccharides were found to protect against allergy development. Objective: The aim of the current study was to examine the effect of anti-CD25-induced Treg depletion in a murine HDM-induced asthma model and to study the contribution of Tregs in the protective effect of dietary intervention with galacto-oligosaccharides. Methods: Male BALB/c mice (aged 6-8 wk) were intranasally sensitized and challenged with phosphate-buffered saline (PBS) or HDM. Two weeks before sensitization and throughout the whole experiment, mice were fed a control or 1% w/w galacto-oligosaccharide diet. Tregs were depleted by anti-mouse CD25 antibody (intraperitoneally injected). On day 14, T helper cell subtypes in lung and spleen were analyzed and cytokines were measured. Leukocyte subtypes were analyzed in the bronchoalveolar lavage fluid, and interleukin (IL)-33 and chemokines were measured in lung homogenate supernatants. Results: Anti-CD25 treatment depleted CD25(+) Forkhead box P3(+) Tregs in the lung and spleen of control and HDM-allergic mice (P < 0.0001) by >70% while increasing the percentage of activated T helper cells (P < 0.05) and type 2 T helper cells (P < 0.05). This was associated with increased IL-10, IL-4, and IL-13 concentrations in supernatants of ex vivo restimulated lung cells (P < 0.01). Bronchoalveolar lavage fluid leukocyte numbers and percentages of eosinophils and lymphocytes were greater in HDM-allergic mice compared with PBS mice (P < 0.01) but remained unaffected by the anti-CD25 treatment. Galacto-oligosaccharides decreased airway eosinophilia compared with HDM-allergic mice fed the control diet (from 47.8% ± 6.7% to 26.6% ± 8.5%, P < 0.01). This protective effect was lost in anti-CD25-treated mice (P < 0.05). In lung homogenates of HDM-allergic mice, IL-33 was increased compared with PBS mice (from 2.8 ± 0.3 to 5.4 ± 0.6 ng protein/mg, P < 0.01). Galacto-oligosaccharides abrogated the increase in IL-33 compared with HDM-allergic mice fed the control diet (3.0 ± 0.6 ng protein/mg, P < 0.05), which was abolished by the anti-CD25 treatment (P < 0.01). Conclusions: Treg depletion enhances pulmonary type 2 T helper cell frequency and cytokine release in HDM-induced asthma in mice. Galacto-oligosaccharides decreased airway eosinophilia and IL-33 concentrations in the lung, which was abrogated by Treg depletion. This indicates that galacto-oligosaccharides have a beneficial effect in the prevention of HDM-induced allergic asthma by supporting pulmonary Treg function.
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Purpose: Thymol and carvacrol, two main components of thyme, have shown anti-inflammatory effects. The aim of this study was to assess the effects of these components on Jurkat leukemia cells as an in vitro T cell model and their molecular mechanisms of activity. Methods: Cells were cultured in the presence of components and subsequently stimulated with phorbol-12-myristate-13-acetate (PMA)/calcium ionophore for evaluating interleukin (IL)-2 and interferon (IFN)-γ production. The activation of T cell transcription factors that included nuclear factors of activated T cells (NFATs), activator protein-1 (AP-1; c-Jun/c-Fos), and nuclear factor (NF)-κB were examined by Western blot analysis. Results: Thymol and carvacrol at 25 µg/ml significantly reduced IL-2 levels from 119.4 ± 8pg/ml in control cells treated only with PMA/Calcium ionophore and the solvent to 66.9 ± 6.4pg/ml (thymol) and 32.3 ± 3.6pg/ml (carvacrol) and IFN-γ from 423.7 ± 19.7pg/ml in control cells to 311.9 ± 11.6pg/ml (thymol) and 293.5 ± 16.7pg/ml (carvacrol). Western blot analyses of nuclear extracts showed that the same concentrations of components significantly reduced NFAT-2 to 44.2 ± 2.7% (thymol) and 91.4 ± 2.3% (carvacrol) of the control (p<0.05), and c-Fos to 31.2 ± 6.2% (thymol) and 27.6 ± 3.1% (carvacrol) of the control (p<0.01). No effects on NFAT-1, c-Jun and phospho-NF-κBp65 levels were observed. Conclusion: Thymol and carvacrol could contribute to modulation of T cell activity by reducing IL-2 and IFN-γ production possibly through down regulation of AP-1 and NFAT-2 transcription factors suggesting their potential usefulness for reduction of T cell overactivity in immune-mediated diseases.
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To investigate the effect of farnesol on allergic asthma, three farnesol doses were extra-added into AIN-76 feed consumed by ovalbumin- (OVA-) sensitized and -challenged mice continuously for 5 weeks, at approximately 5, 25, and 100 mg farnesol/kg, BW/day. The results showed that there were no significant differences in body weight, feed intake, and visceral organ weights between the farnesol supplementation and dietary control groups. Farnesol supplementation decreased interleukin (IL)-6/IL-10 level ratios in bronchoalveolar lavage fluid (BALF). Farnesol supplementation significantly () restored the cytokine secretion ability of peritoneal macrophages that was suppressed as a result of OVA sensitization and challenge and slightly decreased tumor necrosis factor (TNF-α)/IL-10 cytokine secretion ratios. Farnesol supplementation slightly () decreased IL-4 but significantly () increased IL-2 levels secreted by the splenocytes in the presence of OVA, implying that farnesol might have a systemic antiallergic effect on allergic asthmatic mice. Farnesol supplementation significantly () increased IL-10 levels secreted by the splenocytes in the presence of OVA, suggesting that farnesol might have an anti-inflammatory potential to allergic asthmatic mice. Overall, our results suggest that farnesol supplementation may be beneficial to improve the Th2-skewed allergic asthmatic inflammation.
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Inflammation is a crucial factor in the pathogenesis of numerous diseases. This study sought to evaluate the effects of thymol and carvacrol, the main components of Thymus vulgaris (thyme) essential oil, on transcription factors regulating inflammation. Lipopolysaccharide (LPS)-stimulated J774.1 mouse macrophages were examined by real time-PCR for interleukin (IL)-1β and tumor necrosis factor (TNF)-α gene expression in the presence of these compounds. Levels of inducible phospho-nuclear factor-κB (pNF-κB) p65, activator protein-1 [AP-1(c-Fos/c-Jun)], and nuclear factors of activated T-cells (NFATs) were also measured using Western blots. Levels of phosphorylation of stress-activated protein kinases (SAPKs)/c-Jun N-terminal kinase (SAPK/JNK), signal transducer, and activator of transcription (STAT-3), p38, IκBα, and NF-κB p65, as well as total levels of IL-1β and TNFα were determined. The results indicated carvacrol significantly reduced both IL-1β and TNFα at the protein and mRNA levels; thymol also significantly reduced IL-1β expression. Western blot analyses of nuclear cell extracts revealed both agents caused significantly decreased expression of c-Fos, NFAT-1, and NFAT-2; decreased expression of c-Jun was only caused by carvacrol. Neither agent inhibited p-NF-κB p65 expression. At the protein level, carvacrol and thymol each caused decreases in inducible phospho-SAPK/JNK and phospho-STAT3 levels, whereas only carvacrol resulted in increased p-p38 levels in the total cell extract. Despite the reduction of phospho-IκBα caused by both agents, p-NF-κB p65 still increased in the presence of carvacrol. Based on these findings, it is concluded that carvacrol and thymol could contribute to reduction of inflammatory responses through modulation of the expression of JNK, STAT-3, AP-1, and NFATs.
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We have studied the actions of helper T lymphocyte-1 and -2 (Th1 and Th2) cells in an acute model of eosinophilic airway inflammation by infusing chicken ovalbumin-specific (OVA-specific) Th1 cells, Th2 cells, or both into unsensitized mice and challenging the mice with an OVA aerosol. OVA challenge after infusion of Th1 cells alone resulted in airway inflammation with lymphocytes and monocytes. Challenge after the infusion of Th2 cells alone resulted in minimal inflammation. In contrast, when Th1 and Th2 cells were transferred together, they cooperated to promote a robust eosinophil-predominant inflammatory response. Th1 cells alone were readily recruited to the airways after challenge, but in the absence of Th1 cells, Th2 cells did not accumulate in the airways. When transferred together, both Th1 and Th2 cells, as well as endogenous eosinophils, were effectively recruited. This recruitment was correlated with increased VCAM-1 expression in the medium- and large-sized vessels of the lung and could be inhibited by treating the mice with neutralizing antibodies to TNF-alpha or VCAM-1. These data indicate that Th2 cells require signals in addition to antigen for their effective recruitment to the airways. Th1 cells can provide these signals.
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Background: Essential oils are volatile compounds of plant origin increasingly used by allergic and/or asthmatic subjects to purify indoor air. The active compounds of essential oils belong to terpenes, the most widespread biogenic volatile organic compounds (VOC). Although there is substantial literature showing associations between exposure to chemical VOCs and asthmatic symptoms and impaired respiratory function, the impact of essential oils in patients with asthma has never been studied. Objectives: To evaluate the safety of a purifying air spray containing 41 essential oils (PPAS) in patientswith mild or moderate allergic asthma. Methods: This was a prospective open study in which 25 mild (19) and moderate (6) asthmatics were exposed to PPAS, one spray twice a day at 8 am and 8 pm in two different corners of a given subjects bedroom for 4 weeks. Before and after 4 weeks of exposure, fractional exhaled nitric oxide (FeNO), lung function, and methacholine challenge (PD20) were performed and asthma control was assessed by the 5 questions of the Asthma Control Test (ACT). The spray was weighed after the 4-week exposure to assess compliance. Results: FeNO was the primary endpoint and was thus analyzed in all (N = 25) subjects irrespective of the level of airflow obstruction. The results apply to all (N = 25) subjects in which FeNO could be measured at D1 and D30 (17 subjects). Mean (SD) FeNO amounted to 37.4 (16.6) and to 33.1 (18.7) ppm before and after PPAS exposure, respectively (p = 0.09). No significant change in lung function and methacholine responsiveness was noted after PPAS exposure, the mean PD20 amounting to 1179 (1124.42) μg (range 100-3200) before and to 1226 (1189.8) μg (p = 0.06) after. The mean ACT before and after PPAS exposure amounted to 20.9 (4.2) and 21 (5.15), respectively (p = 0.80). The mean weight of the PPAS bottles was 211.4 g (DS:0) before the first use and 171.41g (DS: 29.8) at the end of the study. The average amount of PPAS used was 40.0 gr (29.8). In the subgroup of subjects who used the highest quantities of essential oils (>40 gr), as assessed by the mean weight of the bottle at the end of the study, FeNO after 30 days of exposure decreased more than in the entire group: 7.9 ppm vs 4.2ppm (p = 0.07). Conclusion: No difference was noted on airway inflammation, lung function or asthma control in mild and moderate allergic asthmatics after exposure twice a day for one month, to a spray containing a mixture of 41 essential oils.
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Allergic inflammation is a response of the body against pathogens by cytokine release and leucocyte recruitment. Recently, there was an increase in morbimortality associated with allergic inflammation, especially asthma. The treatment has many adverse effects, requiring the search for new therapies. Monoterpenes are natural products with anti-inflammatory activity demonstrated in several studies and can be an option to inflammation management. Thus, we investigated the effects of citronellol, α-terpineol and carvacrol on allergic inflammation. The model of asthma was established by OVA induction in male Swiss mice. The monoterpenes were administered (25, 50 or 100 mg/kg, i.p.) 1 h before induction. After 24hs, the animals were sacrificed to leucocytes and TNF-α quantification. Monoterpenes significantly decrease leucocyte migration and TNF-α levels, possibly by modulation of COX, PGE2 and H1 receptor, as demonstrated by molecular docking. These findings indicate that alcoholic monoterpenes can be an alternative for treatment of allergic inflammation and asthma.
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Background: Allergic asthma is characterized by inflammation and airway remodelling. Airway remodelling with excessive deposition of extracellular matrix (ECM) and larger smooth muscle mass are correlated with increased airway responsiveness and asthma severity. Calpain is a family of calcium-dependent endopeptidases, which plays an important role in ECM remodelling. However, the role of calpain in airway smooth muscle remodelling remains unknown. Objective: To investigate the role of calpain in asthmatic airway remodelling as well as the underlying mechanism. Methods: The mouse asthma model was made by ovalbumin sensitization and challenge. Calpain conditional knockout mice were studied in the model. Airway smooth muscle cells (ASMCs) were isolated from smooth muscle bundles in airway of rats. Cytokines IL-4, IL-5, TNF-α, and TGF-β1, and serum from patients with asthma were selected to treated ASMCs. Collagen-I synthesis, cell proliferation, and phosphorylation of Akt in ASMCs were analysed. Results: Inhibition of calpain using calpain knockout mice attenuated airway smooth muscle remodelling in mouse asthma models. Cytokines IL-4, IL-5, TNF-α, and TGF-β1, and serum from patients with asthma increased collagen-I synthesis, cell proliferation, and phosphorylation of Akt in ASMCs, which were blocked by the calpain inhibitor MDL28170. Moreover, MDL28170 reduced cytokine-induced increases in Rictor protein, which is the most important component of mammalian target of rapamycin complex 2 (mTORC2). Blockage of the mTORC2 signal pathway prevented cytokine-induced phosphorylation of Akt, collagen-I synthesis, and cell proliferation of ASMCs and attenuated airway smooth muscle remodelling in mouse asthma models. Conclusions and clinical relevance: Our results indicate that calpain mediates cytokine-induced collagen-I synthesis and proliferation of ASMCs via the mTORC2/Akt signalling pathway, thereby regulating airway smooth muscle remodelling in asthma.