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Chemical composition and antinociceptive activity of California sagebrush (Artemisia californica)
Abstract
Artemisia californica, California sagebrush, has been reported to have pain relieving activity and is a traditional medicine of the Chumash Indians of California. Pain relieving activity of a traditional sagebrush preparation was examined in patients suffering from arthritis and other pain. The preparation was examined by gas chromatography-mass spectrometry (GC-MS) and high performance liquid chromatography-mass spectrometry (HPLC-MS) to identify the compounds present. A traditional tincture of sagebrush was produced and used on 42 patients with moderate to severe pain. All patients reported pain relief within 10 to 20 min. Sagebrush was examined by GC-MS and HPLC-MS and was found to contain monoterpenoids, lipids, flavonoids and sesquiterpenes. The major monoterpenoid found is eucalyptol. Of the monoterpenoids, camphor and eucalyptol have reported pain relieving activity. They interact with transient receptor potential cation channel vanilloid 3 (TRPV3), transient receptor potential ankyrin-repeat 1 (TRPA1) and transient receptor potential melastatin 8 (TRPM8) receptors to produce pain relief that lasts for several hours.
... There are reports of many pain patients who were effectively and safely treated (Table 1) with A. californica liniment [17]. Several patients were cured of chronic pain such as fibromyalgia, whiplash and chronic back pain with the liniment [5]. ...
... Many patients make the liniment themselves, for free, in order to treat their arthritis, rheumatoid arthritis, gout, peripheral neuropathy and other conditions. A. californica liniment is also anti-inflammatory by inhibition of neurogenic inflammation and other mechanisms [6,[17][18][19]. Table 1: Patients treated with A. californica as reported in [5,17,20]. ...
... A. californica liniment is also anti-inflammatory by inhibition of neurogenic inflammation and other mechanisms [6,[17][18][19]. Table 1: Patients treated with A. californica as reported in [5,17,20]. Chronic pain is pain of more than 1 month duration. Acute pain is from an injury or other acute event. ...
... Powder of its dried leaves, when taken orally, cures diarrhea [4]. Another crucial member Chrysoplenol, Jaceidin and Jaceosidin [30] Camphor and Eucalyptol [31] α-thujone, artemisia ketone, Camphor, Isothujone and 1,8-cineole [32] A. campestris L. ...
... Limonene, Trans-anethole and Trans-ocimene [34] Trans-ocimene [21] Artemisinin [25] Chavicol, Limonene, Cis-and trans-ocimene, Methyl chavicol and Trans-ocimene [35] α-copaene, α-pinene, α-thujene, 1,8-cineole, Camphene, (E)-β-ocimene, Elemicin, Myrecene, Terpenolene, Trans-Anethole and (Z)-βocimene [36] Camphor, 1,8-cineole [21] 4 Adil Hussain Chrysoplenol, Jaceidin and Jaceosidin [30] Camphor and Eucalyptol [31] α-thujone, artemisia ketone, Camphor, Isothujone and 1,8-cineole [32] A. campestris L. ...
... Artemone, Aromadendrene, α-Pinene, α-Terpinene, α-Terpinyl acetate, Bornyl acetate, β-Pinene, Chrysanthenyl propionate, Camphene, Cis-Davanone, Elixene, 2,3-Dehydro-1,8-cineole, and Santolina alcohol [39] Bornyl acetate, Borneol, Camphor, Eucalyptol and Germacrene-D [42] Camphor and 1,8-cineole [43] 2,2-Dimethyl-6-isopropenyl-2H-pyran, 2,3-dimethyl-6-isopropyl-4H-pyran, 2-isopropenyl-5-methylhexatrans-3,5-diene-1-ol [54] A. verlotiorum Lamotte. α-thujone and Camphor [55] A. vulgaris L. Chrysoplenol, Jaceidin and Jaceosidin [30] Camphor and Eucalyptol [31] α-thujone, artemisia ketone, Camphor, Isothujone and 1,8-cineole [32] A. campestris L. ...
Artemisia is the largest genus in the tribe Anthemideae having ecologically, morphologically, and chemically diverse species. These species are found mostly in the Northern hemisphere, with the distribution of fewer taxa in the Southern hemisphere of the world. Species of this genus have great therapeutic potential and constitute a remarkable natural asset and are still utilized as folk remedies against different health-related problems all over the world. The taxonomy of Artemisia has long been problematic essentially due to the morphological complexities within its species. The recent classification divides the genus into six major groups like Absinthium DC., Artemisia L., Dracunculus Besser, Pacifica, Seriphidium Besser, and Tridantatae (Rydb.) McArthur. However, its infrageneric classification is still indistinguishable. The current review comprehensively enlightens the ethnomedicinal significance and recent advancements in the taxonomy based on foliar anatomy, pollen features, morphology, and molecular phylogeny of Artemisia to understand the classification of this economically significant genus.
... The dilemma with topical pain medicines is to find potent medicines that can treat even severe pain, yet do not have toxicity problems. Sagebrush liniment contains cineole, which is more powerful than morphine [11] and is used by topical application to treat broken bones, gunshot wounds, cancer pain and other severe pain [11,12]. Sagebrush liniment can also provide long-term relief from chronic pain. ...
... The dilemma with topical pain medicines is to find potent medicines that can treat even severe pain, yet do not have toxicity problems. Sagebrush liniment contains cineole, which is more powerful than morphine [11] and is used by topical application to treat broken bones, gunshot wounds, cancer pain and other severe pain [11,12]. Sagebrush liniment can also provide long-term relief from chronic pain. ...
... Chemokines attract macrophages to the skin and induce cyclooxygenase-2 (COX-2) in macrophages, which release prostaglandins. Prostaglandins cause pain by binding to prostaglandin receptors and prolong pain by inducing the phosphorylation of TRP channels [11]. This activates TRP channels and makes them more sensitive to stimuli. ...
Black sage, Salvia mellifera, can be made into a sun tea that is used as a foot soak to treat pain patients. The monoterpenoids and diterpenoids in the preparation penetrate the skin of the feet and stop the pain chemokine cycle, which may be the basis of chronic pain. Several chronic pain patients have reported long-term improvements in their pain after treatment with the preparation.
... The A. californica liniment has been successfully used on patients suffering from broken bones, pain from large abrasions, bruises, sprains, strains, spinal stenosis, osteoarthritis, rheumatoid arthritis, cancer pain, bursitis, muscle pain from over exertion, gout, hip replacement, knee replacement, headaches, migraine headaches, basilar migraines, diabetic neuropathy, shingles, bee stings, a gunshot wound to the abdomen and other conditions [6][7][8]. The S. mellifera sun tea has been successfully used to treat pain from abrasions, bruises, sprains, strains, osteoarthritis, rheumatoid arthritis, bursitis, muscle pain from over exertion, headaches and other conditions [6,9]. ...
... The liniment was made as follows: 86 g of leaves and branches of A. californica, 1 leaf of Salvia apiana, one Persea americana seed and 500 ml of 70% isopropanol were put into a brown glass jar for 6 weeks [7]. The plant material was removed leaving a dark green liniment. ...
... The current report treated pain only in the skin, and provides evidence of improvements in chronic pain. The current report confirms that the safest and most effective way to treat pain is in the skin (2)(3)(4)(5)(6)(7)(8). Of course, the brain and brain stem are involved in processing pain. ...
... The liniment is used by application of small amounts to the skin in the areas where the pain is greatest. A. californica liniment has been used anecdotally in many patients with successful pain relief in every patient [3]. These pain patients suffered from various ailments such as arthritis, muscle and ligament strains, bruises, broken bones, low back pain and cancer. ...
... A recent study [3] of the chemistry of A. californica found 15 monoterpenoids: camphene, mentha-diene, β-pinene, eucalyptol, isopropenylmethylcyclohexanol, trimethylheptadienol, isopropylmethyl-bicyclohexanol, thujanone, thujone, chrysanthenone, camphor, borneol, carene, menthenol and menthadienol [3]. These products were identified by the molecular ions and fragmentation ions obtained by gas chromatography/mass spectrometry. ...
... A recent study [3] of the chemistry of A. californica found 15 monoterpenoids: camphene, mentha-diene, β-pinene, eucalyptol, isopropenylmethylcyclohexanol, trimethylheptadienol, isopropylmethyl-bicyclohexanol, thujanone, thujone, chrysanthenone, camphor, borneol, carene, menthenol and menthadienol [3]. These products were identified by the molecular ions and fragmentation ions obtained by gas chromatography/mass spectrometry. ...
... For instance, if a menthol liniment is applied to the skin, it may not inhibit all of the neuronal terminals in the area, and may not adequately relieve pain. It is important to use a liniment that inhibits as many skin TRPs as possible in order to get pain relief, which may involve multiple monoterpenoids [7][8][9]. ...
... These oral or injected agents do not penetrate adequately into the skin to inhibit skin COX2 [2]. On the other hand, topical sesquiterpenes are known to penetrate the skin and may inhibit COX2 or decrease the expression of COX2 in the skin [7,8]. Topical preparations can be superior to oral or injected preparations for pain treatment. ...
... In contrast, acupuncture is a safe treatment. Various liniments are available to treat pain by topical application [7][8][9]. These liniments are applied where they are needed, work quickly, and are very effective and safe. ...
The most effective and safe treatment site for pain is in the skin. This chapter discusses the reasons to treat pain in the skin. Pain is sensed in the skin through transient receptor potential cation channels and other receptors. These receptors have endogenous agonists (yang) and antagonists (yin) that help the body control pain. Acupuncture works through modulation of these receptor activities (qi) in the skin; as do moxibustion and liniments. The treatment of pain in the skin has the potential to save many lives and improve pain therapy in most patients.
... The liniment also contains the sesquiterpenes leucodin, pestalodiopsolide A, echinolactone B, tanapartholide A and secogorgonolide [26]. These are small, lipophilic compounds that in general can cross the skin. ...
... This provides another way for the liniment to benefit chronic pain patients. The liniment also contains flavonoids and alkaloids that are antiinflammatory [26]. Some flavonoids and alkaloids are known to penetrate the skin and down regulate cyclooxygenase-2. ...
... These compounds add to the analgesic and anti-inflammatory effects of the liniment. The liniment has been used in several hundred patients with success [26]. Patients suffering from broken bones, large abrasions and bruises, spinal stenosis, chronic back pain, fibromyalgia, osteoarthritis, rheumatoid arthritis, cancer pain, bursitis, muscle pain from over exertion, diabetic neuropathy and shingles have been successfully treated. ...
Pain is normally treated with oral nonsteroidal anti-inflammatory agents and opioids. These drugs are dangerous and are responsible for many hospitalizations and deaths. It is much safer to use topical preparations made from plants to treat pain, even severe pain. Topical preparations must contain compounds that penetrate the skin, inhibit pain receptors such as transient receptor potential cation channels and cyclooxygenase-2, to relieve pain. Inhibition of pain in the skin disrupts the pain cycle and avoids exposure of internal organs to large amounts of toxic compounds. Use of topical pain relievers has the potential to save many lives, decrease medical costs and improve therapy.
... Artemisia species are found in many traditional preparations and are frequently used for the treatment of diseases such as malaria, hepatitis, cancer, inflammation, and infections by fungi, bacteria, and viruses [3]. Additionally, Artemisia species are commonly used for their antispasmodic, carminative, and anthelmintic properties [3][4][5][6]. ...
... Artemisia species are found in many traditional preparations and are frequently used for the treatment of diseases such as malaria, hepatitis, cancer, inflammation, and infections by fungi, bacteria, and viruses [3]. Additionally, Artemisia species are commonly used for their antispasmodic, carminative, and anthelmintic properties [3][4][5][6]. ...
... A. judaica contains artemisinic acid, methyl wormwood, artemisinic alcohol, and other essential oils, particularly eucalyptol, artemisia ketone, camphor, caryophyllene, and piperitone [2,14]. Interestingly, it has been suggested that the characteristic composition of its essential oil endorsed Artemisia species such as assorted biological activity [3][4][5][6]. ...
Artemisia judaica L. is a medicinal plant that is traditionally used to relieve abdominal pains through its carminative activity. In this study, spectroscopic analysis was employed to investigate the carminative activity associated with A. judaica. Using infrared spectroscopy, the carminative activity was evaluated based on the first derivative of IR-characteristic stretching signal of CO2. Our results indicate that A. judaica oil effectively reduced the response of CO2 signal equivalent to thymol standard. Additionally, (1)H-NMR spectroscopy was utilized to assess surface activity of A. judaica crude oil through the reduction of interfacial tension in a D2O/CDCl3 system. Apparently, 10 mg of the oil was able to solubilize water in a chloroform layer up to 4.3% (w/w). In order to correlate the observed surface activity of the oil to its actual composition, GC-MS and GC-FID structural analysis were undertaken. The results revealed that the oil composition consists of oxygenated terpenes which might be responsible for the carminative effect. Furthermore, owing to its sensitivity, our model provides a fundamental basis for the pharmacological assessment of trace amounts of oils with high precision and accuracy.
... The liniment is used by application of small amounts to the skin in the areas where the pain is greatest. A. californica liniment has been used anecdotally in many patients with successful pain relief in every patient [3]. These pain patients suffered from various ailments such as arthritis, muscle and ligament strains, bruises, broken bones, low back pain and cancer. ...
... A recent study [3] of the chemistry of A. californica found 15 monoterpenoids: camphene, mentha-diene, β-pinene, eucalyptol, isopropenylmethylcyclohexanol, trimethylheptadienol, isopropylmethyl-bicyclohexanol, thujanone, thujone, chrysanthenone, camphor, borneol, carene, menthenol and menthadienol [3]. These products were identified by the molecular ions and fragmentation ions obtained by gas chromatography/mass spectrometry. ...
... A recent study [3] of the chemistry of A. californica found 15 monoterpenoids: camphene, mentha-diene, β-pinene, eucalyptol, isopropenylmethylcyclohexanol, trimethylheptadienol, isopropylmethyl-bicyclohexanol, thujanone, thujone, chrysanthenone, camphor, borneol, carene, menthenol and menthadienol [3]. These products were identified by the molecular ions and fragmentation ions obtained by gas chromatography/mass spectrometry. ...
The incidence of arthritis is increasing every year, as does the need for pain medication. The current work reviews an American Indian liniment that is traditionally used for pain therapy. The chemistry, therapeutic use and safety of the liniment are reviewed. The liniment contains monoterpenoids, sesquiterpenes, flavonoids, alkaloids and other compounds.
... Topical preparations based on natural products have a long tradition of being applied in the treatment of several conditions, especially pain, in many cultures [7][8][9]. It is very interesting how J 2020, 3 197 many of these traditional remedies against pain seem to contain an abundance of monoterpenoids in their extracts. ...
... It is very interesting how J 2020, 3 197 many of these traditional remedies against pain seem to contain an abundance of monoterpenoids in their extracts. The Chumash Native Americans of California have traditional medicines containing monoterpenoids that are used to cure chronic pain [7][8][9]. There are several mechanisms involved in the actions of monoterpenoids in chronic pain. ...
Ointments and lotions from natural extracts have a long tradition of being used in folk medicines against pain conditions. Monoterpenoids are among the major constituents of several natural topical remedies. The field of chronic pain is one of the most investigated for new active molecular entities. This review will discuss several molecular mechanisms against which monoterpenoids have been proven to be good candidates for the topical treatment of chronic pain.
... The smell comes from the 15 monoterpenoids in the plant. (Adams, 2012b;Fontaine et al., 2013) A. californica is used to make a liniment that is a powerful pain reliever (Adams, 2012b;Fontaine et al., 2013). The monoterpenoids in the plant interact with transient receptor potential cation channels to relieve pain. ...
... The smell comes from the 15 monoterpenoids in the plant. (Adams, 2012b;Fontaine et al., 2013) A. californica is used to make a liniment that is a powerful pain reliever (Adams, 2012b;Fontaine et al., 2013). The monoterpenoids in the plant interact with transient receptor potential cation channels to relieve pain. ...
Modern society suffers from a disease burden that is caused by out of balance patients. Obesity causes patients to be out of balance and develop diseases such as heart disease, diabetes, and arthritis. Obesity also promotes cancer. Traditional medicine can help people learn how to live in balance. When a person is in balance, the body heals itself. This article teaches the advantages of traditional healing in the modern world.
... Two cures for chronic pain have been reported, a liniment made from Artemisia californica and a foot bath made from Salvia mellifera [8][9][10]. The liniment has been shown to be superior to placebo [11]. ...
The brain stem and brain are involved in chronic pain processing and sensation. This may involve changes in gene expression through epigenetic alterations [1]. Chronic pain is also a learned experience which involves the brain [2]. In chronic pain, thresholds to pain sensation decrease such that pain may be produced by nonpainful stimuli.
... 1. Leucodin, a-santonin and sclareolide structures. Fontaine et al., 2013) is part of the pseudoguaianolides group. It is characterized by a cyclopentadienone rigid ring system. ...
Plants of the Asteraceae family have been used in traditional medicine for centuries due to their main antimicrobial and analgesic activities. A liniment from Artemisia californica has recently been tested on patients affected by either acute pain or chronic pain conditions with great success.
The aim of this study was to evaluate the anti-inflammatory activity of sesquiterpene lactones (SLs), representing the majority in the Asteraceae family. Leucodin, α-santonin and sclareolide (three SLs) were chosen to undergo chemical modifications. This pool of molecules underwent molecular modeling experiments using an in-house program, WATGEN, predicting the water network and its contribution to the overall affinity of the enzyme-ligand complex. The anti-inflammatory activity and the ability of compounds to modulate COX-2 expression have been evaluated in LPS-stimulated RAW 264.7 cells and in RIF-1 cells treated according to the Photodynamic Therapy (PDT) protocols using Photoprin (PH) as photosensitizer. Furthermore, commercially available assay kits were used to evaluate the concentration of PGE-2 and the direct inhibition of COX-2. All the tested molecules fit well in the enzyme binding pocket, but to get a substantial inhibition of the expression and activity of the enzyme as well as a reduction in the PGE2 concentration, high concentrations of the compounds are needed. The only exceptions being leucodin itself and FP6, one of the α-santonin derivatives, presenting a CF3 functional group. We believe that this class of compounds has some interesting potential in the treatment of pain and inflammation. Although, the activity seems to be due to a mechanism related to the expression of the COX enzymes rather than on a direct inhibition.
... Costanoan Indians applied leaves to wounds or aching teeth for pain reduction, used a decoction to bathe patients with colds, coughs and rheumatism, or consumed leaves and used them as a poultice for treatment of asthma (Bocek 1984). California sagebrush contains a variety of monoterpenoids, flavonoids, and sesquiterpenes, some of which have medicinal value; of the monoterpenoid compounds, camphor and eucalyptol react with pain receptors to reduce pain (Fontaine et al. 2013). ...
... As other Artemisia species, A. judaica is found in many traditional preparations to treat inflammation and infections caused by fungi, bacteria, and viruses (Fontaine et al., 2013;Alzweiri et al.,2014). ...
Ethnopharmacologic relevance:
Artemisia judaica L. (Arabic name: Beithran), is a medicinal and aromatic plant growing in the valley bottoms of desert areas, particularly in the southern desert of Jordan nearest to the Jordan-Saudi Arabia borders and in Wadi Araba in the Southern Badia. In Jordan, A. judaica is widely used in traditional medicine being recommended by aboriginal Bedouins in the North Badia region of Jordan as calmative. Furthermore, it is used for the treatment of stomach ache, heart diseases, sexual weakness, diabetes, gastro-intestinal disorders and external wounding. Additionally, other folk medicines of the Arabic region commonly use this aromatic plant for the treatment of inflammatory-related diseases, for instance fungal infections, diabetes, atherosclerosis, cancer and arthritis.
Aim of the study:
Considering the traditional medicinal uses and the lack of scientific studies addressing the cellular and molecular mechanisms behind A. judaica claimed activities, the present study was designed to validate some of the traditional uses ascribed to this species, specifically the antifungal and anti-inflammatory activities of A. judaica essential oil at doses devoid of cytotoxicity to mammalian cells.
Materials and methods:
Chemical analysis of A. judaica essential oil isolated by hydrodistillation from aerial parts was carried out by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). The antifungal activity (minimal inhibitory concentrations and minimal lethal concentrations) was evaluated against yeasts, dermatophyte and Aspergillus strains. In order to deeply explore the mechanisms behind the anti-fungal effect of the essential oil, the germ tube inhibition assay and the biofilms formation assay were evaluated using Candida albicans. The assessment of cell viability was accomplished using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in both hepatocytes and macrophages. Furthermore, the in vitro anti-inflammatory potential of A. judaica oil was evaluated by measuring nitric oxide (NO) production using lipopolysaccharide (LPS)-stimulated mouse macrophages.
Results:
Oxygen containing monoterpenes are a representative group of constituents (68.7%) with piperitone (30.4%), camphor (16.1%) and ethyl cinnamate (11.0%) as main compounds. The highest antifungal activity of the oil was observed against Cryptococcus neoformans, with a MIC value of 0.16µL/mL. The oil revealed an important inhibitory effect on germ tube formation in C. albicans with 80% inhibition of filamentation at a concentration of 0.16µL/mL. Importantly, the oil also interfered with pre-formed biofilms by reducing the amount of the attached biomass. Furthermore, the essential oil significantly inhibited NO production evoked by LPS on macrophages at concentrations with very low toxicity (0.32µL/mL) or without toxicity (0.16µL/mL) to both macrophages and hepatocytes.
Conclusions:
The present study revealed that A. judaica essential oil from Jordan significantly inhibited germ tube formation and disrupted preformed biofilms of C. albicans, emphasizing the therapeutic potential for the treatment of disseminated candidiasis. Additionally, safe concentrations of this essential oil significantly inhibited NO production elicited by LPS in macrophages, highlighting its potential anti-inflammatory activity. Overall, A. judaica bears promising therapeutic potential for further drug development. Importantly, this work also validates some of the traditional uses of A. judaica.
This paper is typically intended to carefully collect and properly review the antinociceptive activities of medicinal plants. In this review article, by searching keywords of medicinal plants, pain, herbal medicine, antinociceptive, phytotherapy in databases of Web of Science, Scopus, Google Scholar, Springer, Wiley, Proquest, PubMed, Nature, Magiran, Emerald, SID, ISI, and some other indexing cites, or traditional books, desired articles were obtained until 2021. The title of medicinal plants was searched diligently in Persian and English. Ultimately, 270 articles were studied. The findings possibly indicated that several medicinal plants are among the most valuable plants that have antinociceptive activities. There efficiently are various antinociceptive compounds in medicinal plants. The antinociceptive activity of these specific compounds may be through their peculiar effects on the opioid system, cholinergic pathways, and stimulation of GABA receptors, with the peripheral and central antinociceptive mechanism. Antiinflammatory processes, inhibition of the synthesis, and the release of arachidonic acid, prostaglandins, phospholipase, nitric oxide, and cyclooxygenase‐2 have been reported as analgesic mechanisms of some herbs. In a reasonable conclusion, our review thoughtfully provides a comprehensive summary of present data from some scientific studies on the common herbs with antinociceptive and antiinflammatory activities.
Ethno-pharmacological relevance
Artemisia judaica L is an aromatic medicinal plant growing widely in Saint Katherine, Sinai, Egypt, and used in traditional medicine as a herbal remedy for antibacterial, anthelmintic, antidiabetic, analgesic and anti-inflammatory, activities. Additionally, other Arabic regions commonly used it in their folk medicines for the treatment of fungal infections, atherosclerosis, cancer, diabetes, arthritis, and inflammatory-related diseases.
Aim of the study
Based on the traditional medicinal uses of A. judaica, the present study was designed to validate some of the traditional uses as an analgesic, anti-inflammatory, the antipyretic, hepatoprotective, antidiabetic, and antioxidant activity of 80% aqueous methanol extract (AME) of A. judaica aerial part as well as isolation and identification of its flavonoid content.
Materials and methods
AME of A. judaica aerial part was fractionated using column chromatography and the structures of the isolated compounds were established using different spectroscopic data. Analgesic activity was evaluated using acetic acid-induced writhing in mice; antipyretic was assessed using yeast suspension-induced hyperthermia in rats; anti-inflammatory activity was evaluated using carrageenan-induced paw edema; the hepatoprotective effect was studied by measuring liver enzymes in carbon tetrachloride(CCl4)-induced hepatotoxicity rats while antidiabetic activity was estimated in alloxan hyperglycemia.
Results
Eight flavone compounds namely luteolin 4` methyl ether 7-O-β-D-⁴C1-glucopyranoside (1), 8-methoxyapigenin 7-O-β-D-⁴C1-galactopyranoside (2), isovitexin (3), 8-methoxyluteolin 7-O-β-D-⁴C1-glucopyranoside (4), diosmetin (5), cirsimaritin (6), luteolin (7), and apigenin (8) were identified from AME of A. judaica. The AME was found to be non-toxic to mice up to 5 g/kg b.w. moreover, it exhibits significant analgesic antipyretic, anti-inflammatory, antidiabetic, hepatoprotective, and antioxidant activity in a dose-dependent manner.
Conclusion
The AME was nontoxic; it exhibits significant analgesic antipyretic, anti-inflammatory, antidiabetic, hepatoprotective, and antioxidant activity. Moreover, the isolated flavone was identified from AME for the first time.
Several reviews have been published on Artemisia's derived natural products, but it is the first attempt to review the chemistry and pharmacology of more than 80 alkaloids and allied nitrogen compounds obtained from various Artemisia species (covering the literature up to June 2018). The pharmacological potential and unique skeleton types of certain Artemisia's alkaloids provoke the importance of analyzing Artemisia species for bioactive alkaloids and allied nitrogen compounds. Among the various types of bioactive Artemisia's alkaloids, the main classes were the derivatives of rupestine (pyridine-sesquiterpene), lycoctonine (diterpene), pyrrolizidine, purines, polyamine, peptides, indole, piperidine, pyrrolidine, alkamides, and flavoalkaloids. The rupestine derivatives are Artemisia's characteristic alkaloids, whereas the rest are common alkaloids found in the family Asteraceae and chemotaxonomically links the genus Artemisia with the tribes Anthemideae. The most important biological activities of Artemisia's alkaloids are including hepatoprotective, local anesthetic, β-galactosidase, and antiparasitic activities; treatment of angina pectoris, opening blocked arteries, as a sleep-inducing agents and inhibition of HIV viral protease, CYP450, melanin biosynthesis, human carbonic anhydrase, [3H]-AEA metabolism, kinases, and DNA polymerase β1 . Some of the important nitrogen metabolites of Artemisia include pellitorine, zeatin, tryptophan, rupestine, and aconitine analogs, which need to be optimized and commercialized further.
Background: Opioidal analgesics are one of the most important drugs that have been widely used in attenuating moderate to severe pain. Unfortunately, the problems of long term use of opiods are tolerance, dependence, and ultimately addiction to mentioned drugs. Glial cells (microglia and astrocyte) and pro-inflammatory cytokines are important factors in morphine tolerance and withdrawal symptoms. It has been demonstrated that Artemisia austriaca extract has antinociceptive and anti-inflammatory properties. In this study the effect of total methanolic extract of aerial parts of Artemisia austrica on withdrawal syndrome of morphine in male rats has been evaluated. Methods: Adult male Wistar rats were rendered morphine-dependent by injection of additive doses of morphine subcutaneously twice daily for 9 days. To determine the effect of Artemisia austriaca extract on morphine withdrawal syndrome, 12 hours after the last injection of morphine, different doses of the methanolic extract of Artemisia austriaca (100, 200, 400 mg/kg, i.p.) dissolved in (%25DMSO in saline), was injected and after 30 minutes, naloxone (4 mg/kg, i.p.) was injected and withdrawal signs were recorded for 45 minutes. Results: The results showed that methanolic extract of Artemisia austriaca could reduce the morphine withdrawal symptoms in a dose-dependent manner. Conclution: The results of the present study indicate that Artemisia austriaca has beneficial effects in reducing withdrawal syndrome of morphine. The underlying mechanisms of this effect may consist of reduction of inflammatory response and attenuating of pro-inflammatory cytokines activation by its alkaloids content.
Diverse fungal species live inside plant tissues, some of which presumably occur in a mutualistic association. Some fungal endophytes are widespread and can be found in many different plant species, whereas others are highly specific to single hosts. In this study, we investigated the taxonomic identities and phylogenetic relationships of fungal endophytes isolated from three plant species, Artemisia capillaris, A. indica, and A. lactiflora, using a combination of morphological and molecular approaches. Morphological differences among the fungal isolates indicate that diverse distinct morphotypes might be present within the hosts. Thirty-four fungal isolates were selected for further molecular phylogenetic analysis using nuclear ribosomal DNA sequences, including both the internal transcribed spacers (ITS1 and ITS2) and the 5.8S gene region. The 34 endophytes were identified to various taxonomic levels, and some to the species level based on fungal sequences with known identities in GenBank. Our results suggest that Alternoria, Colletotrichum, Phomopsis, and Xylaria species are the dominant fungal endophytes in the Artemisia hosts, and some of these endophytes exhibit host and tissue specificity. This aspect can be further explored to understand the relationships between plant hosts and their fungal endophytes.
Aereal parts of three Asteraceae from Iran have been analysed for exudate flavonoids. Artemisia oliveriana, Pulicaria gnaphalodes and Tanacetum polycephalum are shown to accumulate mostly 6-methoxylated flavonols and flavones as external aglycones.
A simple and specific analytical method for the quantitative determination of flavonoids from the aerial parts of the Artemisia afra plant samples was developed. By column high-performance liquid chromatography (HPLC) with UV absorption and mass spectrometry (MS) detection, separation was achieved on a reversed-phase octadecylsilyl (C18) column with water, methanol, and acetonitrile, all containing 0.1% acetic acid, as the mobile phase. These methods were used to analyze various species of Artemisia plant samples. The wavelength used for quantification of flavonoids with the diode array detector was 335 nm. The limits of detection (LOD) by HPLC/MS were found to be 7.5, 7.5, 10, 2.0, and 2.0 ng/mL; and by LC-UV the LODs were 500, 500, 500, 300, and 300 ng/mL for apigenin, chrysoeriol, tamarixetin, acacetin, and genkwanin, respectively. The HPLC/MS method was found to be 50-150 times more sensitive than the HPLC-UV method. HPLC/MS coupled with an electrospray ionization interface is described for the identification and quantification of flavonoids in various plant samples. This method involved the use of the [M+H]+ ions of the compounds at mass-to-charge ratio of 1.0606, 301.0712, 317.0661, 285.0763, and 285.0763 (calculated mass), respectively, in the positive ion mode with extractive ion monitoring.
The rationale of this investigation was to examine the antinociceptive properties of the essential oil obtained from Rosmarinus officinalis aerial parts, using a rat model of arthritic pain. The essential oil (100, 300 and 600 mg/kg, I. P.) produced a dose-dependent antinociceptive effect, manifested as a significant reduction in the dysfunction in the pain-induced functional impairment model in the rat (PIFIR model), mainly at high doses. Chemical constituents of the essential oil were further analyzed by gas chromatography-mass spectrometry (GC/MS). The major compounds in the essential oil were alpha-pinene (14.10 %), camphene (11.47 %), beta-pinene (12.02 %), myrcene (3.31 %), alpha-phellandrene (7.87 %), eucalyptol (8.58 %), 2-bornanone (3.42 %), camphor (8.75 %), isoborneol (3.48 %), borneol (4.85 %) and borneol acetate (6.49 %). The antinociceptive effects of R. officinalis essential oil were tested in combination with 0.12 mg/kg WAY100635, s. c. (an antagonist of 5-HT(1A) receptors) or 1 mg/kg naloxone, i. p. (an antagonist of endogenous opioids receptors), demonstrating in both cases an inhibition of the antinociceptive response. This study suggests an involvement, at least in part, of the serotonergic system via 5-HT(1A) receptors and endogenous opioids in the antinociceptive effect of R. officinalis essential oil in the PIFIR model.
The investigation of a dichloromethane extract of flower heads of a Hungarian taxon of the Achillea millefolium group led to the isolation of three flavonoid aglycones, one triterpene, one germacranolide and five guaianolides. Their structures were elucidated by UV-VIS, EI- and CI-MS, 1H NMR and 13C NMR spectroscopic methods as well as by 2D-NMR studies and by selective 1D-NOE experiments. Besides apigenin, luteolin and centaureidin, beta-sitosterol, 3beta-hydroxy-11alpha,13-dihydro-costunolide, desacetylmatricarin, leucodin, achillin, 8alpha-angeloxy-leucodin and 8alpha-angeloxy-achillin were isolated. Both latter substances are reported here for the first time. Their NMR data were compared with those of the other guaianolides. The stereochemistry of 3beta-hydroxy-11alpha,13-dihydro-costunolide was discussed and compared with data of the literature.
A Pestalotiopis sp. was isolated from the trunk bark of Pinus taeda. The fungus was cultivated in liquid medium and produced three highly oxygenated caryophyllene sequiterpene derivatives, named pestalotiopsolide A, taedolidol and 6-epitaedolidol, respectively. The sesquiterpenes were isolated by silica gel based chromatographic procedures and their structures were elucidated by NMR spectroscopic data.
Camphor is a naturally occurring compound that is used as a major active ingredient of balms and liniments supplied as topical analgesics. Despite its long history of common medical use, the underlying molecular mechanism of camphor action is not understood. Capsaicin and menthol, two other topically applied agents widely used for similar purposes, are known to excite and desensitize sensory nerves by acting on two members of transient receptor potential (TRP) channel superfamily: heat-sensitive TRP vanilloid subtype 1 (TRPV1) and cold-sensitive TRP channel M8, respectively. Camphor has recently been shown to activate TRPV3, and here we show that camphor also activates heterologously expressed TRPV1, requiring higher concentrations than capsaicin. Activation was enhanced by phospholipase C-coupled receptor stimulation mimicking inflamed conditions. Similar camphor-activated TRPV1-like currents were observed in isolated rat DRG neurons and were strongly potentiated after activation of protein kinase C with phorbol-12-myristate-13-acetate. Camphor activation of rat TRPV1 was mediated by distinct channel regions from capsaicin, as indicated by camphor activation in the presence of the competitive inhibitor capsazepine and in a capsaicin-insensitive point mutant. Camphor did not activate the capsaicin-insensitive chicken TRPV1. TRPV1 desensitization is believed to contribute to the analgesic actions of capsaicin. We found that, although camphor activates TRPV1 less effectively, camphor application desensitized TRPV1 more rapidly and completely than capsaicin. Conversely, TRPV3 current sensitized after repeated camphor applications, which is inconsistent with the analgesic role of camphor. We also found that camphor inhibited several other related TRP channels, including ankyrin-repeat TRP 1 (TRPA1). The camphor-induced desensitization of TRPV1 and block of TRPA1 may underlie the analgesic effects of camphor.
A review of national poison center data from 1990 through 2003 showed approximately 10,000 annual ingestion exposures to camphor-containing products. A guideline that determines the threshold dose for emergency department referral and need for prehospital decontamination could potentially avoid unnecessary emergency department visits, reduce health care costs, optimize patient outcome, and reduce life disruption for patients and caregivers. An evidence-based expert consensus process was used to create the guideline. Relevant articles were abstracted by a trained physician researcher. The first draft of the guideline was created by the primary author. The entire panel discussed and refined the guideline before distribution to secondary reviewers for comment. The panel then made changes based on the secondary review comments. The objective of this guideline is to assist poison center personnel in the appropriate out-of-hospital triage and initial management of patients
1,8-cineole (cineole) and beta-pinene, two monoterpenes isolated from the essential oil obtained from Eucalyptus camaldulensis Dehn leaves were tested for antinociceptive properties. Tail-flick and hot-plate methods, reflecting the spinal and supraspinal levels, respectively, were used in mice and/or rats using morphine and naloxone for comparison. Cineole exhibited an antinociceptive activity comparable to that of morphine, in both algesic stimuli. A significant synergism between cineole and morphine was observed, but naloxone failed to antagonize the effect of cineole. Beta-pinene exerted supraspinal antinociceptive actions in rats only and it reversed the antinociceptive effect of morphine in a degree equivalent to naloxone, probably acting as a partial agonist through the mu opioid receptors. From structure-activity relationships of the pairs morphine+cineole and naloxone+beta-pinene, it was shown that similarities exist in the stereochemistry and in the respective atomic charges of these molecules. Further studies are in progress in order to elucidate the mechanism of action of the two terpenoids.
Flavonoid glycosides (22 compounds) were measured by fast atom bombardment, and the positive and negative ion mass spectra were compared. The mass spectra showed clear molecular ion species. Fast atom bombardment mass spectrometry provided useful information for the structural elucidation of flavonoid glycosides.Positive ion spectra in particular were useful for flavonol 3,7-O-diglycosides, while the negative ion spectra were useful for flavonoid glycoside methyl ether.
The assignments of the 1H and 13C NMR spectra of the 3-deoxyanthocyanins apigeninidin-5-glucoside and luteolinidin-5-glucoside, present in petals of the Gesneriad Sinningia cardinalis are presented. The resonances were assigned using 1D (1H, 13C, 13C-DEPT) and 2D (DQF COSY, HSQC, HMBC) NMR techniques. Copyright © 2000 John Wiley & Sons, Ltd.
A total of eleven naturally occurring guaianolides, 11 beta,13-dihydrokauniolide, estafiatin, isodehydrocostuslactone, 2-oxodesoxyligustrin, arborescin, 11 beta,13-dihydroludattin, 8-deoxy-11 beta,13-dihydrorupicolin B, ludartin, kauniolide, dehydroleucodin, and leucodin, and three related compounds, 1,10-epiarborescin, 8-deoxyrupicolin B, and 3,4-epiludartin, were synthesized through a common cationic intermediate A, which was derived from (11S)-1 beta-(mesyloxy)eudesm-3-eno-12,6 alpha-lactone [2] by solvolytic rearrangement.
Artecalin (I), a sesquiterpene lactone of the Santanolide group, has been found in Artemisia californica Less. (section Abrotanum) and in A. tripartita Gray ssp. rupicola Beetle (section Seriphidium). By removal of the elements of water, artecalin is converted into tuberiferin, a constituent of a plant of the tribe Cichorieae.
The nervous system detects and interprets a wide range of thermal and mechanical stimuli, as well as environmental and endogenous chemical irritants. When intense, these stimuli generate acute pain, and in the setting of persistent injury, both peripheral and central nervous system components of the pain transmission pathway exhibit tremendous plasticity, enhancing pain signals and producing hypersensitivity. When plasticity facilitates protective reflexes, it can be beneficial, but when the changes persist, a chronic pain condition may result. Genetic, electrophysiological, and pharmacological studies are elucidating the molecular mechanisms that underlie detection, coding, and modulation of noxious stimuli that generate pain.
This study investigated the analgesic and anti-inflammatory effects of a water extract of Trachelospermum jasminoides (WET) in ICR mice.
In HPLC analysis, the fingerprint chromatogram of WET was established. Acetic acid-induced writhing response and formalin-induced pain were examined the analgesics effects of WET. WET on lambda-Carrageenan(carr)-induced paw edema was performed. We investigate the anti-inflammatory mechanism of WET via studies of the activities of glutathione peroxidase (GPx), glutathione reductase (GRx) in the liver and the levels of malondialdehyde (MDA) and nitrite oxide (NO) in the edema paw. Serum NO and TNF-alpha were also measured.
The fingerprint chromatogram of WET was established through HPLC analysis, and implies that WET contains the active ingredient gallic acid, chlorgenic acid, caffeic acid, taxifolin, isoquercitrin and quercetin. WET significantly inhibited the numbers of acetic acid-induced writhing responses and the formalin-induced pain in the late phase. In the anti-inflammatory test, WET inhibited the development of paw edema induced by carr. WET decreased the paw edema at the third, fourth and fifth hour after carr administration, and increased the activities of SOD, GPx and GRx in the liver tissue and decreased the MDA level in the edema paw at the third hour after carr injection. WET decreased the level of NO in edematous paw tissue and in serum level, and diminished the level of serum TNF-alpha at the fifth hour after carr injection.
These results demonstrated that WET is an effective anti-inflammatory agent in carr-induced inflammation. WET probably exerts anti-inflammatory effects by suppressing TNF-alpha and NO. The anti-inflammatory mechanism of WET might be related to the decrease in the level of MDA in the edema paw via increasing the activities of SOD, GPx and GRx in the liver.
Eupatilin (5,7-dihydroxy-3',4',6-trimethoxyflavone) is the major lipophilic flavonoid from Artemisia umbelliformis Lam. and Artemisia genipi Weber, two mountain wormwoods used for the production of the celebrated alpine liqueur genepy. The topical anti-inflammatory activity of eupatilin was investigated using the inhibition of the Croton-oil-induced dermatitis in the mouse ear as the end point. The oedematous response and the leukocyte infiltration were evaluated up to 48 h after the induction of phlogosis, comparing eupatilin with hydrocortisone and indomethacin as representatives of steroid and non-steroid anti-inflammatory drugs, respectively. At maximum development, eupatilin significantly reduced edema in a dose-dependent manner (ID(50) = 0.28 micromol/cm(2)), showing an anti-inflammatory potency comparable to that of indomethacin (ID(50) = 0.26 micromol/cm(2)) and only 1 order of magnitude lower than that of hydrocortisone (ID(50) = 0.03 micromol/cm(2)). Within 48 h, eupatilin (0.30 micromol/cm(2)) caused a global inhibition of the oedematous response (42%) higher than that of an equimolar dose of indomethacin (18%) and fully comparable to that of 0.03 micromol/cm(2) of hydrocortisone (55%). Moreover, the effect of eupatilin on the granulocytes infiltrate (32% inhibition) was similar to that of indomethacin (35% inhibition) and comparable to that of hydrocortisone (42% reduction), as confirmed by histological analysis. When our results are taken together, they show that eupatilin is endowed with potent in vivo topical anti-inflammatory activity, qualitatively similar to that of hydrocortisone and intermediate in terms of potency between those of steroid and non-steroid drugs.
For essential oils, several biological effects such as antibacterial, anti-inflammatory, expectorant, and blood-circulation-enhancing properties have been described. The method of application depends on the pathophysiology, the desired outcome, safety, and toxicity data. For treating respiratory symptoms and nervous disorders, inhalation may be the best means of application, whereas topical application is the best way for treating skin diseases. For dermal application, percutaneous absorption of essential oil and oil components is of great interest. Essential oils are complex mixtures of different volatile substances. So, the question is raised whether all components of a complex composed essential oil are equivalent with respect to their human skin permeation. By means of artificial mixtures of different essential oil ingredients, we investigated the cooperative effect of monoterpenes and phenylpropanoids on the permeation through heat-separated human skin epidermis in static Franz-Diffusion Cells. Limonene showed an enhancing effect on the permeation of citronellol and eugenol. Both alpha-pinene and myrcene increased the apparent permeability ( P(app)) value of phenylethanol. beta-Pinene had an enhancing effect on the permeation behaviour of methyleugenol but not of geraniol. The investigations clearly show that cooperative effects of single essential oil components may influence percutaneous essential oil absorption.
Depending on their primary structure, the 28 mammalian transient receptor potential (TRP) cation channels identified so far can be sorted into 6 subfamilies: TRPC ("Canonical"), TRPV ("Vanilloid"), TRPM ("Melastatin"), TRPP ("Polycystin"), TRPML ("Mucolipin"), and TRPA ("Ankyrin"). The TRPV subfamily (vanilloid receptors) comprises channels critically involved in nociception and thermosensing (TRPV1, TRPV2, TRPV3, and TRPV4), whereas TRPV5 and TRPV6 are involved in renal Ca(2+) absorption/reabsorption. Apart from TRPV1, the pharmacology of these channels is still insufficiently known. Furthermore, only few small-molecule ligands for non-TRPV1 vanilloid receptors have been identified, and little is known of their endogenous ligands, resulting in a substantial "orphan" state for these channels. In this review, we summarize the pharmacological properties of members of the TRPV subfamily, highlighting the critical issues and challenges facing their "deorphanization" and clinical exploitation.
Tilia species are well known around the world for their properties in traditional medicine. Antinociceptive activity of hexane, methanol and aqueous extracts from Tilia americana var. mexicana inflorescences was evaluated in the pain-induced functional impairment model in rats (PIFIR). A preliminar 300 mg/kg dosage of aqueous extracts i.p., but not the same dose of methanol or hexane extract, produced an antinociceptive response in rats similar to that of tramadol (17.8 mg/kg i.p.). A dose-response curve from aqueous extract allowed the determination of ED(50) = 364.97 mg/kg in comparison to ED(50) = 10.35 mg/kg for tramadol in this model. A previous HPLC-DAD analysis corroborated by an HPLC-MS technique in this study demonstrated the flavonoid composition in this Tilia aqueous extract revealing the presence of glycosides mainly derived from quercetin. Thus, Tilia aqueous extract and quercetin were tested at 30 and/or 100 mg/kg dosages i.p. in the PIFIR and formalin models producing a significant and dose-dependent antinociceptive response resembling that produced by a total and a partial agonist of 5-HT(1A) receptors like 8-OH-DPAT (0.1 mg/kg, s.c.) and buspirone (5 mg/kg, i.p.), respectively. In all the treatments, antinociceptive response was inhibited in the presence of WAY 100635 (0.12 mg/kg, i.p.). Our results support the analgesic activity of T. americana var. mexicana inflorescences attributed by folk medicine; they also indicate that quercetin is partly responsible for this pharmacological activity that is likely mediated by serotonin 5-HT(1A) receptors.
Leaves and flowers of Artemisia gorgonum (Asteraceae) collected in Fogo, Cape Verde islands, were phytochemically investigated and resulted in isolation and characterization of three guaianolides 1, 2, 5, and a secoguainolide 4, in addition to eight known guaianolides 6-11 and two known germacranolides 12, 13. Structures were elucidated by 1D and 2D NMR experiments. Careful examination of the (13)C NMR spectrum led to revision of the structure of a previously described guaianolide from 2 to 3. Most compounds exhibited mild antiplasmodial activities, ridentin (13) being the most interesting with an IC(50) of 3.8+/-0.7microgml(-1) against Plasmodium falciparum FcB1 and weak cytotoxicity in a vero cell line (IC(50) 71.0+/-3.9microgml(-1)).
Artemisia vestita is a common traditional Tibetan medicinal plant which has been used widely in China for treating various inflammatory diseases. Since little is known about its active components, the purpose of this study was to isolate and identify the immunosuppressive compounds from Artemisia vestita.
A bioassay-guided isolation was performed with picryl chloride-induced contact hypersensitivity in mice. MTT assay and Flow cytometric analysis were used for determining Con A-induced lymphocyte proliferation and CD25 expression in T cells, respectively.
The ethanol extract of the Artemisia vestita was found to possess significant inhibitory activity against the picryl chloride-induced contact hypersensitivity in mice. Then 4 fractions were isolated by macroporous adsorption resin and one of these fractions (AV3), which showed the highest activity in in vivo test, was further subjected to column chromatography. Nine known flavones were isolated and identified as pectolinarigenin (1), jaceosidin (2), cirsilineol (3), cirsimaritin (4), hispidulin (5), quercetin (6), 6-methoxytricin (7), acacetin (8), and apigenin (9). The structures of the 9 flavones were elucidated by spectral techniques. All the compounds were evaluated for their inhibitory activity on the proliferation and activation of T cells in vitro. Among the 9 flavones, cirsilineol (3), 6-methoxytricin (7) and apigenin (9) significantly inhibited T cell proliferation and activation in the bioassays.
The result suggests that cirsilineol, 6-methoxytricin and apigenin are the major active components in Artemisia vestita.
Alpha-thujone is the toxic agent in absinthe, a liqueur popular in the 19th and early 20th centuries that has adverse health effects. It is also the active ingredient of wormwood oil and some other herbal medicines and is reported to have antinociceptive, insecticidal, and anthelmintic activity. This study elucidates the mechanism of alpha-thujone neurotoxicity and identifies its major metabolites and their role in the poisoning process. Four observations establish that alpha-thujone is a modulator of the gamma-aminobutyric acid (GABA) type A receptor. First, the poisoning signs (and their alleviation by diazepam and phenobarbital) in mice are similar to those of the classical antagonist picrotoxinin. Second, a strain of Drosophila specifically resistant to chloride channel blockers is also tolerant to alpha-thujone. Third, alpha-thujone is a competitive inhibitor of [(3)H]ethynylbicycloorthobenzoate binding to mouse brain membranes. Most definitively, GABA-induced peak currents in rat dorsal root ganglion neurons are suppressed by alpha-thujone with complete reversal after washout. alpha-Thujone is quickly metabolized in vitro by mouse liver microsomes with NADPH (cytochrome P450) forming 7-hydroxy-alpha-thujone as the major product plus five minor ones (4-hydroxy-alpha-thujone, 4-hydroxy-beta-thujone, two other hydroxythujones, and 7,8-dehydro-alpha-thujone), several of which also are detected in the brain of mice treated i.p. with alpha-thujone. The major 7-hydroxy metabolite attains much higher brain levels than alpha-thujone but is less toxic to mice and Drosophila and less potent in the binding assay. The other metabolites assayed are also detoxification products. Thus, alpha-thujone in absinthe and herbal medicines is a rapid-acting and readily detoxified modulator of the GABA-gated chloride channel.
Sage (Salvia libanotica) is an East Mediterranean plant, the extract of which is used for the treatment of colds, coughs, and stomach ache. Experimental studies on the toxicity of its oil are scarce despite its wide use in traditional medicine. This study aims to provide data on its acute toxicity and to investigate the relationship between seasonal changes in oil composition and toxicity. The composition of the oil extract from the leaves of this plant was determined at four different times of the year; August (summer), October (fall), January (winter) and April (spring). The toxicity of each fraction was investigated following intraperitoneal (i.p.) injection into mice. Distillations of oils from plants and GC analyses revealed that the main constituent of sage oil is 1,8-cineole. Other components included ketones such as camphor and alpha,beta-thujone, terpenes such as limonene and alpha,beta-pinene, and alcohols such as borneol and linalool. Major seasonal changes were found in the composition of the oil. Essential oil extracted from plants collected in the winter season (January) contained higher levels of camphor (12.3%), alpha,beta-thujone (1.9%), and camphene (4.8%). The winter extract was found to be the most toxic, (LD(50): 839 mg/kg body weight) and exhibited powerful convulsant properties. This indicates a strong correlation between the contents of camphor, thujones and camphene and the oils' toxicity. The spring extract was the least toxic (LD(50): 1200 mg/kg body weight) and contained lower levels of camphor (7.7%), alpha,beta-thujone (1.3%) and camphene (3.1%). Thus, we recommend that oil extracts of sage marketed for use in certain unconventional medicines be prepared from spring plants.
The leaf essential oil of Laurus nobilis Linn., Lauraceae, which has been used as an antiepileptic remedy in Iranian traditional medicine, was evaluated for anticonvulsant activity against experimental seizures. The essential oil protected mice against tonic convulsions induced by maximal electroshock and especially by pentylenetetrazole. Components responsible for this effect may be methyleugenol, eugenol and pinene present in the essential oil. At anticonvulsant doses, the essential oil produced sedation and motor impairment. This effect seems to be related in part to cineol, eugenol and methyleugenol. Although the essential oil had an acceptable acute toxicity, further studies are required before any absolute conclusions can be drawn.
Effects of common monoterpenoid alcohols and ketones were investigated on recombinant human gamma-aminobutyric acid A (GABAA; alpha1beta2gamma2s) and glycine (alpha1 homomers) receptors expressed in Xenopus oocytes. GABA currents were enhanced by coapplications of 10-300 microM: (+)-menthol>(-)-menthol>(-)-borneol>(-)-menthone=camphor enantiomers>carvone enantiomers, with menthol acting stereoselectively. By contrast, thujone diastereomers inhibited GABAA receptor currents while glycine currents were only markedly potentiated by menthol. Positive modulation by (+)-menthol was explored given its pronounced effects (e.g., at 100 microM, GABA and glycine EC20 responses increased by 496+/-113% and 135+/-56%, respectively). (+)-Menthol, 100 microM, reduced EC50 values for GABA and glycine from 82.8+/-9.9 to 25.0+/-1.8 microM, and from 98.7+/-8.6 to 75.7+/-9.4 microM respectively, with negligible effects on maximal currents. This study reveals a novel neuroactive role for menthol as a stereoselective modulator of inhibitory ligand-gated channels.
(+)-Borneol is a bicyclic monoterpene used for analgesia and anaesthesia in traditional Chinese and Japanese medicine and is found in the essential oils of medicinal herbs, such as valerian. (+)-Borneol was found to have a highly efficacious positive modulating action at GABA(A) receptors, as did its enantiomer (-)-borneol. The effects of these bicyclic monoterpenes alone and with GABA were evaluated at recombinant human alpha(1)beta(2)gamma(2L) GABA(A) receptors expressed in Xenopus laevis oocytes using two-electrode voltage-clamp electrophysiology. (+)-Borneol (EC(50) 248microM) and (-)-borneol (EC(50) 237microM) enhanced the action of low concentrations of GABA by more than 1000%. These enhancing effects were highly dependent on the relative concentrations of the borneol enantiomer and GABA, and were insensitive to flumazenil indicating that (+)- and (-)-borneol were not acting at classical benzodiazepine sites. The maximal responses to GABA were enhanced 19% by (+)-borneol and reduced 21% by (-)-borneol. The borneol analogues isoborneol, (-)-bornyl acetate and camphor, produced less marked effects. At high concentrations (>1.5mM) (+)- and (-)-borneol directly activated GABA(A) receptors producing 89% and 84%, respectively, of the maximal GABA response indicative of a weak partial agonist action. Although of lower potency, the highly efficacious positive modulatory actions of (+)- and (-)-borneol on GABA responses were at least equivalent to that of the anaesthetic etomidate and much greater than that of diazepam or 5alpha-pregnan-3alpha-ol-20-one. The relatively rigid cage structure of these bicyclic monoterpenes and their high efficacy may aid in a greater understanding of molecular aspects of positive modulation of the activation of GABA(A) receptors.
Illudalane sesquiterpenoids, echinolactones A and B, were isolated from the culture broth of the fungus Echinodontium japonicum, and their structures spectroscopically determined.
We developed a strategy for determination and quantification of glycosyl flavonoids using liquid chromatography-triple quadrupole mass spectrometry with neutral loss scan at 15 and 30eV collision energy in the positive ion mode. The fragmentation patterns of glycosyl flavonoids at 15 and 30eV showed that fragmentation of sugar moiety depended on the type of glycosidic bond to aglycone, the site of C-glycosylation, and the type of aglycone. C-Glycosyl dihydrochalcones especially stood out because they produced [M+H-162](+) even at 15eV such as O-glycoside in spite of C-glycoside. C-Glycosides were classified according to (i) the intensity ratio A of [M+H-150](+) to [M+H-120](+) at 30eV and (ii) the intensity ratio B of [M+H-120](+) at 15eV to one at 30eV. The 8-C-glycosides were A<1 and B<1, the 6-C-glycosides were A>1 and B<1, and the C-glycosyl dihydrochalcones were A>1 and B>1. Therefore, the intensity ratios of the neutral loss scan of 120 and 150Da at 30eV and those of 120, 162, and 308Da at 15eV allowed sequential distinction among these three types of C-glycosides as well as between O- and C-glycosides. Our method was applied for analysis of Rooibos tea, and the identified glycosides could be quantified specifically by the selected reaction monitoring method.
This review article summarizes our knowledge of the metabolism of mono- and sesquiterpenoids in mammals, microorganisms, cloned-insect enzymes, and plant-cultured cells. A number of unusual enzymatic reactions and products are reported such as the stereoselective formation of primary alcohols from sterically congested Me2C groups. Such enzymatic processes, including unknown chemical transformations under abiotic conditions, could lead to the discovery of new chemical reactions and might be helpful in the design of new drugs. The transformations of the following mono- and sesquiterpenoids (in alphabetical order) are discussed: (+)-(1R)-aromadendrene (61), (-)-allo-aromadendrene (62), (+/-)-camphene (21), (-)-cis-carane (20), (+)-3-carene (17), (+/-)-carvone (27), (-)-beta-caryophyllene (43), (+)-cedrol (35), cuminaldehyde (25), (+)-curdione (69), (-)-cyclocolorenone (60), (-)-elemol (51), (2E,6E)-farnesol (31), germacrone (67), ginsenol (40), (-)-globulol (63), isoprobotryan-9alpha-ol (82a), juvenile hormone III (33), (+)-ledol (65), (+)-longifolene (46), myrcene (3), (-)-myrtenal (23), (+)-nootkatone (48), patchouli alcohol (37), (-)-perillaldehyde (24), (-)-alpha- and beta-pinene (8 and 9), alpha-santalol (28), (-)-6beta-santonin (83a), 6beta-tetrahydrosantonin (83b), beta-selinene (57), alpha-thujone (26a), beta-thujone (26b), T-2 toxin (87), and valerianol (53).
Transient receptor potential (TRP) V3 is a thermosensitive ion channel expressed predominantly in the skin and neural tissues. It is activated by warmth and the monoterpene camphor and has been hypothesized to be involved in skin sensitization. A selection of monoterpenoid compounds was tested for TRPV3 activation to establish a structure-function relationship. The related channel TRPM8 is activated by cool temperatures and a number of chemicals, among them the monoterpene (-)-menthol. The overlap of the receptor pharmacology between the two channels was investigated.
Transfected HEK293 cells were superfused with the test substances. Evoked currents were measured in whole cell patch clamp measurements. Dose-response curves for the most potent agonists were obtained in Xenopus laevis oocytes.
Six monoterpenes significantly more potent than camphor were identified: 6-tert-butyl-m-cresol, carvacrol, dihydrocarveol, thymol, carveol and (+)-borneol. Their EC(50) is up to 16 times lower than that of camphor. All of these compounds carry a ring-located hydroxyl group and neither activates TRPM8 to a major extent.
Terpenoids have long been recognized as medically and pharmacologically active compounds, although their molecular targets have only partially been identified. TRPV3 activation may be responsible for several of the described effects of terpenoids. We show here that TRPV3 is activated by a number of monoterpenes and that a secondary hydroxyl-group is a structural requirement.
Three anti-inflammatory compounds: nepetin, jaceosidin and hispidulin have been isolated and identified from Eupatorium arnottianum Griseb. dichloromethane extract. Nepetin reduced the TPA mouse ear edema by 46.9% and jaceosidin by 23.2% (1mg/ear). Both compounds inhibited the NF kappaB induction by 91 and 77%, respectively. Furthermore phytochemical analysis of the ethanol extract has led to the identification of eriodictyol, hyperoside, rutin, caffeic and chlorogenic acids. All these compounds are reported for the first time in this species. The finding of topical antiinflammatory activity exerted by Eupatorium arnottianum extract and the identification of active principles could support the use of this plant for the treatment of inflammatory affections.
In this study, chemical compositions of hydrodistilled essential oil and anti-inflammatory activities from the twigs of Cinnamomum osmophloeum Kaneh. were investigated for the first time. The chemical constituents of the twig essential oil were further analyzed by GC-MS and they were found to be L-bornyl acetate (15.89%), caryophyllene oxide (12.98%), gamma-eudesmol (8.03%), beta-caryophyllene (6.60%), T-cadinol (5.49%), delta-cadinene (4.79%), trans-beta-elemenone (4.25%), cadalene (4.19%), and trans-cinnamaldehyde (4.07%). The effects of essential oil on nitric oxide (NO) and prostaglandin E2 (PGE2) production in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages were also examined. Results of nitric oxide tests indicated that twig essential oil and its major constituents such as trans-cinnamaldehyde, caryophyllene oxide, L-borneol, L-bornyl acetate, eugenol, beta-caryophyllene, E-nerolidol, and cinnamyl acetate have excellent activities. These findings demonstrated that essential oil of C. osmophloeum twigs have excellent anti-inflammatory activities and thus have great potential to be used as a source for natural health products.
To evaluate the measurement properties of a new osteoarthritis (OA) pain measure.
The new tool, comprised of 12 questions on constant vs intermittent pain was administered by phone to 100 subjects aged 40+ years with hip or knee OA, followed by three global hip/knee questions, the Western Ontario and McMaster Universities (WOMAC) pain subscale, the symptom subscales of the Hip Disability and OA Outcome Score (HOOS) or Knee Injury and OA Outcome Score (KOOS), and the limitation dimension of the Late Life Function and Disability Instrument (LLFDI). Test-retest reliability was assessed by re-administration after 48-96h. Item response distributions, inter-item correlations, item-total correlations and Cronbach's alpha were assessed. Principle component analysis was performed and test-retest reliability was assessed by intra-class correlation coefficient (ICC).
There was good distribution of response options across all items. The mean intensity was higher for intermittent vs constant pain, indicating subjects could distinguish the two concepts. Inter-item correlations ranged from 0.37 to 0.76 indicating no item redundancy. One item, predictability of pain, was removed from subsequent analyses as correlations with other items and item-total correlations were low. The 11-item scale had a corrected inter-item correlation range of 0.54-0.81 with Cronbach's alpha of 0.93 for the combined sample. Principle components analysis demonstrated factorial complexity. As such, scoring was based on the summing of individual items. Test-retest reliability was excellent (ICC 0.85). The measure was significantly correlated with each of the other measures [Spearman correlations -0.60 (KOOS symptoms) to 0.81 (WOMAC pain scale)], except the LLFDI, where correlations were low.
Preliminary psychometric testing suggests this OA pain measure is reliable and valid.
Herba Artemisiae Scopariae is a Chinese herbal medicine widely used for the remedy of liver diseases. A high performance liquid chromatography method coupled with diode array detection was developed to simultaneously determine 13 different bioactive compounds in Herba Artemisiae Scopariae (Yin Chen) including chlorogenic acid (1), 6,7-dihydroxycoumarin (2), caffeic acid (3), 4-hydroxyacetophenone (4), scopoletin (5), rutin (6), hyperoside (7), isoquercitrin (8), scoparone (11), 7-methoxycoumarine (12) and quercetin (13). By using four different wavelengths in the HPLC analysis, the developed method was able to determine the bioactive compounds with excellent resolution, precision and recovery. The method was applied to determine the amounts of the bioactive compounds in nine samples from different cultivated regions and harvest seasons in China, and significant variations were revealed. Chlorogenic acid was the most abundant among the analyzed compounds. The samples harvested in the spring contained higher contents of chlorogenic acid than those collected in other seasons. Other phenolic acids as caffeic acid, 3,5-dicaffeoylquinic acid, 4,5-dicaffeoylquinic acid and 4-hydroxyacetophenone accumulated at much higher amounts in about May to July. The samples analyzed contained a much lower level of the amount of other flavonoids and coumarins as rutin, hyperoside, isoquercitrin and scoparone.
In this study, the fruit essential oil of Cinnamomum insularimontanum was prepared by using water distillation. Followed by GC-MS analysis, the composition of fruit essential oil was characterized. The main constituents of essential oil were alpha-pinene (9.45%), camphene (1.70%), beta-pinene (4.30%), limonene (1.76%), citronellal (24.64%), citronellol (16.78%), and citral (35.89%). According to the results obtained from nitric oxide (NO) inhibitory activity assay, crude essential oil and its dominant compound (citral) presented the significant NO production inhibitory activity, IC(50) of crude essential oil and citral were 18.68 and 13.18microg/mL, respectively. Moreover, based on the results obtained from the protein expression assay, the expression of IKK, iNOS, and nuclear NF-kappaB was decreased and IkappaBalpha was increased in dose-dependent manners, it proved that the anti-inflammatory mechanism of citral was blocked via the NF-kappaB pathway, but it could not efficiently suppress the activity on COX-2. In addition, citral exhibited a potent anti-inflammatory activity in the assay of croton oil-induced mice ear edema, when the dosage was 0.1 and 0.3mg per ear, the inflammation would reduce to 22% and 83%, respectively. The results presented that the fruit essential oil of C. insularimontanum and/or citral may have a great potential to develop the anti-inflammatory medicine in the future.
Although the medicinal plant Artemisia rupestris L. has been widely researched for several decades, its alkaloids have never been isolated before. To our surprise, the alkaloids in the plant were not detected in the stems but detected in the flowers. Herein, a novel and strange guaipyridine sesquiterpene alkaloid with a carboxyl group named rupestine was purified successfully from the total alkaloids extracted from the flowers by high-speed counter-current chromatography (HSCCC). The two-phase solvent system used was composed of ethyl acetate-methanol-water (8:1:7, v/v/v). Fifty six milligrams of rupestine was obtained at over 97% purity and 95% recovery from 200 mg of the total alkaloids in one-step separation. Its structure was elucidated by spectroscopic methods including high resolution ESI-MS, (1)H NMR, (13)C NMR, Heteronuclear Multiple Bond Correlation (HMBC), Heteronuclear Single Quantum Coherence (HSQC), and Nuclear Overhauser Enhancement Spectroscopy (NOESY).
The capsaicin receptor: a heat-activated ion channel in the pain pathway
- M J Caterina
- M A Schumacher
- M Tominaga
- T A Rosen
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Julius D (1997). The capsaicin receptor: a heat-activated ion channel
in the pain pathway. Nature 389:816-824.
Healing with Medicinal Plants of the West-Cultural and Scientific Basis for Their Use Third Edition
- C Garcia
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Garcia C, Adams J (2012). Healing with Medicinal Plants of the West-Cultural and Scientific Basis for Their Use Third Edition. Abedus
Press: La Crescenta.
Antinociceptive effect and GC/MS analysis of Rosmarinus officinalis L. essential oil from its aerial parts
- A L Martinez
- M E Gonzalez-Trujano
- F Pellicer
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Artemisolide from Artemisia asiatica
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- J Y Lee
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- C K Lee
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Reddy AM, Lee JY, Seo JH, Kim BH, Chung EY, Ryu SY, Kim YS, Lee
CK, Min KR, Kim Y (2006). Artemisolide from Artemisia asiatica;