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Natural products (NPs) have played a vital role in human survival for millennia, particularly for their medicinal properties. Many traditional medicine practices continue to utilise crude plants and animal products for treating various diseases, including inflammation. In contrast, contemporary medicine focuses more on isolating drug-lead compounds from NPs to develop new and better treatment drugs for treating inflammatory disorders such as inflammatory bowel diseases. There is an ongoing search for new drug leads as there is still no cure for many inflammatory conditions. Various approaches and technologies are used in drug discoveries from NPs. This review comprehensively focuses on anti-inflammatory small molecules and describes the key strategies in identifying, extracting, fractionating and isolating small-molecule drug leads. This review also discusses the (i) most used approaches and recently available techniques, including artificial intelligence (AI), (ii) machine learning, and computational approaches in drug discovery; (iii) provides various animal models and cell lines used in in-vitro and in-vivo assessment of the anti-inflammatory potential of NPs. [ABSTRACT FROM AUTHOR]

Traditional medicinal plants have been used for decades in folk medicines in the treatment and management of several ailments and diseases including diabetes, pain, ulcers, cancers, and wounds, among others. This study focused on the phytochemical and antidiabetic activity of the commonly used antidiabetic medicinal species in Kenya. Phytochemical profiling of these species revealed flavonoids and terpenoids as the major chemical classes reported which have been linked with strong biological activities against the aforementioned diseases, among others. However, out of the selected twenty-two species, many of the natural product isolation studies have focused on only a few species, as highlighted in the study. All of the examined crude extracts from thirteen antidiabetic species demonstrated strong antidiabetic activities by inhibiting α-glucosidase and α-amylase among other mechanisms, while nine are yet to be evaluated for their antidiabetic activities. Isolated compounds S-Methylcysteine sulfoxide, quercetin, alliuocide G, 2-(3,4-Dihydroxybenzoyl)-2,4,6-trihydroxy-3 (2H)-benzofuranone, Luteolin-7-O-D-glucopyranoside, quercetin, 1,3,11α-Trihydroxy-9-(3,5,7-trihydroxy-4H-1-benzopyran-7-on-2-yl)-5α-(3,4-dihydroxy-phenyl)-5,6,11-hexahydro-5,6,11-trioxanaphthacene-12-one and [1,3,11α-Trihydroxy-9-(3,5,7-trihydroxy-4H-1-benzopyran-7-on-2-yl)-5α-(3,4-dihydroxy-phenyl)-5,6,11-hexahydro-5,6,11-trioxanaphthacene-12-one]-4′-O-D-gluco-pyranoside from Allium cepa have been found to exhibit significant antidiabetic activities. With the huge number of adults living with diabetes in Kenya and the available treatment methods being expensive yet not so effective, this study highlights alternative remedies by documenting the commonly used antidiabetic medicinal plants. Further, the study supports the antidiabetic use of these plants with the existing pharmacological profiles and highlights research study gaps. Therefore, it is urgent to conduct natural products isolation work on the selected antidiabetic species commonly used in Kenya and evaluate their antidiabetic activities, both in vitro and in vivo, to validate their antidiabetic use and come up with new antidiabetic drugs. [ABSTRACT FROM AUTHOR]

The archipelagic country of Indonesia is inhabited by 300 ethnic groups, including the indigenous people of Tengger. Based on the reported list of medicinal plants used by the Tengger community, we have reviewed each of them for their phytochemical constituents and pharmacological activities. Out of a total of 41 medicinal plants used by the Tengerrese people, 33 species were studied for their phytochemical and pharmacological properties. More than 554 phytochemicals with diverse molecular structures belonging to different chemical classes including flavonoids, terpenoids, saponins and volatiles were identified from these studied 34 medicinal plants. Many of these medicinal plants and their compounds have been tested for various pharmacological activities including anti-inflammatory, antimicrobial, wound healing, headache, antimalarial and hypertension. Five popularly used medicinal plants by the healers were Garcinia mangostana, Apium graveolens, Cayratia clematidea, Drymocallis arguta and Elaeocarpus longifolius. Only A. graviolens were previously studied, with the outcomes supporting the pharmacological claims to treat hypertension. Few unexplored medicinal plants are Physalis lagascae, Piper amplum, Rosa tomentosa and Tagetes tenuifolia, and they present great potential for biodiscovery and drug lead identification. [ABSTRACT FROM AUTHOR]

Australian tropical plants have been a rich source of food (bush food) and medicine to the first Australians (Aboriginal people), who are believed to have lived for more than 50,000 years. Plants such as spreading sneezeweed (Centipeda minima), goat's foot (Ipomoea pes-caprae), and hop bush (Dodonaea viscosa and D. polyandra) are a few popular Aboriginal medicinal plants. Thus far, more than 900 medicinal plants have been recorded in the tropical region alone, and many of them are associated with diverse ethnomedicinal uses that belong to the traditional owners of Aboriginal people. In our effort to find anti-inflammatory lead compounds in collaboration with Aboriginal communities from their medicinal plants, we reviewed 78 medicinal plants used against various inflammation and inflammatory-related conditions by Aboriginal people. Out of those 78 species, we have included only 45 species whose crude extracts or isolated pure compounds showed anti-inflammatory properties. Upon investigating compounds isolated from 40 species (for five species, only crude extracts were studied), 83 compounds were associated with various anti-inflammatory properties. Alphitolic acid, Betulinic acid, Malabaric acid, and Hispidulin reduced proinflammatory cytokines and cyclooxygenase enzymes (COX-1 and 2) with IC50 values ranging from 11.5 to 46.9 uM. Other promising anti-inflammatory compounds are Brevilin A (from Centipeda minima), Eupalestin, and 5′-methoxy nobiletin (from Ageratum conyzoides), Calophyllolide (from Calophyllum inophyllum), and Brusatol (from Brucea javanica). D. polyandra is one example of an Aboriginal medicinal plant from which a novel anti-inflammatory benzoyl ester clerodane diterpenoid compound was obtained (compound name not disclosed), and it is in the development of topical medicines for inflammatory skin diseases. Medicinal plants in the tropics and those associated with indigenous knowledge of Aboriginal people could be a potential alternative source of novel anti-inflammatory therapeutics. [ABSTRACT FROM AUTHOR]

The floristic study along the Sherichhu River was carried out to determine the riparian plant species diversity and distribution pattern. A total of 34 study plots were laid on either side of the riverbank and recorded 72 woody species belonging to 52 families and 61 genera. Based on ocular inspections and topography, the areas were categorised into U-shaped and V-shaped valley. These two valleys, though differing in topography, has fostered the existence of diverse plant species in the study area. A considerable variation in the species diversity and richness was observed between the V-shaped and U-shaped regions based on the Shannon diversity index (P = 0.013) and species richness (P = 0.005) values. The Importance Value Indices (IVI) were highest for Desmodium elegans, Mallotus philippensis, and Rhus paniculata in the V-shaped area and Murraya koenigii Duabanga grandiflora and Quercus glauca had the highest IVI in the U-shaped area. Fabaceae, Euphorbiaceae, Anacardiaceae exhibited a high family value index (FVI) in the V-shaped area, while the U-shaped area had a high FVI for Rutaceaec, Lythraceae, Fagaceae, and Myrtaceae. Structurally, the Mallotus-Desmodium-Rhus community was dominant in the V-shaped area, while Duabanga-Terminalia-Murraya and Quercus-glauca woodland communities were dominant in U-shaped valley. The CCA analysis revealed that the slope and litter thickness had shown greater influence on the plant species composition. In general, topography, micro-habitat conditions, river channel width, and flood regimes may have influenced riparian plant species diversity and distribution patterns. Thus, identifying key plant community types and underlying environmental conditions may help to accomplish and safeguard forest resources in the area. Riparian vegetation along the Sherichhu River is also a habitat for medicinal plants (11 out of 72 woody species), a source of food and income to rural communities. Thus, future studies should also focus on devising appropriate strategies for protecting and conserving Bhutan's riparian ecosystem from global warming. [ABSTRACT FROM AUTHOR]

The Meru Betiri National Park in Indonesia is host to more than 266 medicinal plants species, of which 10 were investigated for their phytochemicals as well as antioxidant and antimicrobial activities. A majority of the tested plant species contained polyphenols. The crude leaf extracts of Dioscorea esculenta possessed the highest antioxidant activity with IC50 of 26.8 µg mL−1. Escherichia coli was sensitive to Bryophyllum pinnatum and Hibiscus tilliaceus leaf extracts with similar minimum inhibition concentration (MIC) of 250 µg mL−1. Klebsiella pneumoniae was sensitive to Moringa oleifera leaf extract with MIC of 125 µg mL−1. Staphylococcus aureus was the most sensitive to leaf extracts of Hibiscus tilliaceus with MIC of 62.5 µg mL−1, Pseudomonas aeruginosa was sensitive to Lunasia amara leaf extract with MIC of 125 µg mL−1. Autobiographic TLC confirmed the presence of anti-microbial constituents in L. amara leaf extract. [ABSTRACT FROM AUTHOR]

In this study, 71 species of edible medicinal plants belonging to 49 families were identified. These medicinal plants (beside therapeutic applications inSowa Rigpamedicine) are used as food, fruit and vegetables in Bhutan. Five Himalayan medicinal plants were further studied for their phenolic content and antioxidant activity.Hypecoum leptocarpumHook. f. & Thompson contained maximum phenolic content. The antioxidant activities were determined by DRSA and FRAP assays from water and methanol extracts. Overall, among five plants investigated,Lepisorus contortus(Christ) Ching,H. leptocarpumandPodophyllum hexandrumRoyle gave good yield of phenolics content and best antioxidant activity. This study demonstrates that edible medicinal plants could be a potential source of natural antioxidants that can boost the immune system. [ABSTRACT FROM PUBLISHER]

In this work, total phenolic and flavonoid contents and antioxidant activities in methanol and aqueous extracts of five-high altitude medicinal plants namelyAconogonon tortuosum, Thlaspi arvense, Erysimum bhutanicum, Thalictrum chelidoniiandAletris pauciflorawere studied for the first time from Bhutan. Antioxidant activities were investigated using DPPH radical scavenging activity (DRSA), ferric reducing antioxidant power (FRAP), superoxide dismutase (SOD) and catalase (CAT) assays. Significant level of phenolics and flavonoids were found in all medicinal herbs. Among the five plants studied, aqueous extract ofThalictrum chelidoniiand methanol extract ofErysimum bhutanicumshowed best free radical scavenging activity. Both aqueous and methanol extracts ofAconogonon tortuosumshowed strong ferric reducing antioxidant power. The results indicate that all five medicinal herbs could be potential sources of natural antioxidant compounds and could help boost the immune system of patients. [ABSTRACT FROM AUTHOR]

Bhutanese traditional medicine (BTM) is an integral part of the mainstream health care system in Bhutan. It uses more than 230 species of medicinal plants, including the Meconopsis species. Although traditional BTM methods are used to check the quality of medicinal plants, these methods have limitations in differentiating the closely related species. There is a need for integrating traditional methods with modern analytical techniques to efficiently monitor the quality and safety of medicinal plants. Here, we studied two closely related Meconopsis species using both traditional and modern analytical approaches. Meconopsis horridula Hook. F & Thompson and Meconopsis simplicifolia (D. Don) Walpers were collected from Lingzhi, Bhutan. The samples were tested and compared for physicochemical properties and extractive values. Their microscopy and High-Performance Thin-Layer Chromatography (HPTLC) profiles were also compared. A literature review was performed to document isolated phytochemicals and their biological activities. Two Meconopsis species revealed distinct macro-and microscopic characteristics. The physicochemical analysis and the HPTLC fingerprinting generated adequate data to authenticate these two species while preparing 16 essential traditional medicine drugs (ETMDs) in BTM. A literature review revealed that the two Meconopsis species contain alkaloids and flavonoids, which can be used as biomarker compounds for quality screening. M. horridula and M. simplicifolia could be differentiated based on their taxonomical features, macroscopic and microscopic characteristics, HPTLC fingerprint profiles, and physicochemical values. The accomplished pharmacognostic properties of the two species can be used as important parameters in ensuring the quality and safety of BTM. [ABSTRACT FROM AUTHOR]

Background: Whipworms and blood flukes combined infect almost one billion people in developing countries. Only a handful of anthelmintic drugs are currently available to treat these infections effectively; there is therefore an urgent need for new generations of anthelmintic compounds. Medicinal plants have presented as a viable source of new parasiticides. Ajania nubigena, the Bhutanese daisy, has been used in Bhutanese traditional medicine for treating various diseases and our previous studies revealed that small molecules from this plant have antimalarial properties. Encouraged by these findings, we screened four major compounds isolated from A. nubigena for their anthelmintic properties. Methodology/Principal Findings: Here we studied four major compounds derived from A. nubigena for their anthelmintic properties against the nematode whipworm Trichuris muris and the platyhelminth blood fluke Schistosoma mansoni using the xWORM assay technique. Of four compounds tested, two compounds—luteolin (3) and (3R,6R)-linalool oxide acetate (1)—showed dual anthelmintic activity against S. mansoni (IC50 range = 5.8–36.9 μg/mL) and T. muris (IC50 range = 9.7–20.4 μg/mL). Using scanning electron microscopy, we determined luteolin as the most efficacious compound against both parasites and additionally was found effective against the schistosomula, the infective stage of S. mansoni (IC50 = 13.3 μg/mL). Luteolin induced tegumental damage to S. mansoni and affected the cuticle, bacillary bands and bacillary glands of T. muris. Our in vivo assessment of luteolin (3) against T. muris infection at a single oral dosing of 100 mg/kg, despite being significantly (27.6%) better than the untreated control group, was markedly weaker than mebendazole (93.1%) in reducing the worm burden in mice. Conclusions/Significance: Among the four compounds tested, luteolin demonstrated the best broad-spectrum activity against two different helminths—T. muris and S. mansoni—and was effective against juvenile schistosomes, the stage that is refractory to the current gold standard drug, praziquantel. Medicinal chemistry optimisation including cytotoxicity analysis, analogue development and structure-activity relationship studies are warranted and could lead to the identification of more potent chemical entities for the control of parasitic helminths of humans and animals. [ABSTRACT FROM AUTHOR]

Background: The traditional g.so-ba-rig-pa hospitals in Bhutan uses more than 100 polyingredient medicines that are manufactured by the Menjong Sorig Pharmaceuticals (MSP). The MSP has been collecting medicinal plants from Lingzhi region for about 48 years and therefore the ecological pressure on these plants have increased. It is MSP's top priority to identify an alternative collection site to ease the problem. Therefore, this study was carried out to determine whether Dagala region could potentially be an alternative collection site for MSP. Methods: First the multidisciplinary research team generated a tentative plant list by reviewing a body of ancient g.so-ba-rig-pa literature, current formulations, and the MSP medicinal plants inventory documents. Second, the research team visited the study areas in Dagala region for spot identification of medicinal plants. Third, we confirmed our traditional and botanical identification by crosschecking the descriptions with the series of books on traditional texts, Flora of Bhutan, scientific papers on medicinal plants, and the plant databases. Results: We have identified 100 species of high altitude medicinal plants from Dagala region. Of these, 24 species grow abundantly, 29 species grow in moderate numbers and 47 species were scarce. More than 85 species belonged to the herbaceous life form and 51 of them are used as a whole plant. A total of 68 species grow in between 4000 and 4999 meter above sea level. These 100 medicinal plants represented 39 different families and 80 genera and the maximum number of plants belonged to the family Asteraceae. Of 60 species that are currently used for formulating medicines at MSP, 16 species have economic importance with potential for commercial collection. Out of seven areas covered by the survey, Kipchen hosted maximum number of medicinal plants (21 species). Conclusions: Our survey identified 100 medicinal plants from Dagala region and of these, 16 species has economic potential that could benefit both MSP and Dagala communities. It is feasible to establish an alternative medicinal plants collection center in Dagala Gewog. [ABSTRACT FROM AUTHOR]

Background: The medicinal plants and the associated Bhutanese traditional medicine (BTM) are protected by the country's constitution and receive both government support and acceptance by the wider public. More than 1000 medicinal plants are described in the BTM but currently collects only 300 species for daily formulations of BTM. These medicinal plants have been one of the drivers of the 'Gross National Happiness (GNH)' and biodiscovery projects in Bhutan. However, no review covering the systematic evaluations of the contributions of medicinal plants and the BTM to the GNH and biodiscovery exist till date. Methods: This paper, therefore addresses this information gap. It is based on the review of the existing traditional and scientific literature, government websites and policy documents. The descriptions and discussions of the paper is straightened, authenticated and enhanced by the data collected through the informal discussions with the BTM practitioners and also through the authors' many years of practical observations of the impact of the medicinal plants programs and the BTM practices in Bhutan. Results: This paper found the following: a) the medicinal plants generates income to the farmers elevating their living standard and the economic status, b) it serves as the bulk ingredients of the BTM facilitating the provision of free traditional health care services to the patients, c) helps the conservation of medicinal plants and their pristine environment through recognition of their spiritual, social and economic values, d) preserves the rich BTM cultural heritage, and e) guides the biodiscovery projects based on their ethnobotanical information. The paper also identified the challenges and research gaps, and recommends appropriate strategies that can help secure the sustainable future of the medicinal plants, the BTM and the biodiscovery projects. Conclusions: The medicinal plants play significant role in the country's bio discovery projects and the internationally renowned development policy of 'Gross National Happiness'. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: The aerial components of Meconopsis simplicifolia (D. Don) Walpers are indicated in Bhutanese traditional medicine for treating malaria, coughs and colds, and the infections of the liver, lung and blood. This study is to validate the ethnopharmacological uses of this plant and also identify potent antimalarial drug leads through bioassays of its crude extracts and phytochemical constituents. Materials and methods: Meconopsis simplicifolia (D. Don) Walpers was collected from Bhutan and its crude MeOH extract was subjected to acid-base fractionation. Through repeated extractions, separations and spectroscopic analysis, the alkaloids obtained were identified and tested for their antimalarial and cytotoxicity activities. Results: Phytochemical studies resulted in the isolation of one new protoberberine type alkaloid which we named as simplicifolianine and five known alkaloids: protopine, norsanguinarine, dihydrosanguinarine, 6-methoxydihydrosanguinarine and oxysanguinarine. Among the five of the alkaloids tested, simplicifolianine showed the most potent antiplasmodial activities against the Plasmodium falciparum strains, TM4/8.2 (chloroquine–antifolate sensitive strain) and K1CB1 (multidrug resistant strain) with IC 50 values of 0.78μg/mL and 1.29μg/mL, respectively. The compounds tested did not show any significant cytotoxicity activities against human oral carcinoma KB cells and normal Vero cells of African kidney epithelial cells. Conclusions: This study validated the traditional uses of the plant for the treatment of malaria and identified a new alkaloid, simplicifolianine as a potential antimalarial drug lead. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: Seven studied medicinal plants; Aconitum laciniatum, Ajania nubigena, Codonopsis bhutanica, Corydalis crispa, Corydalis dubia, Meconopsis simplicifolia and Pleurospermum amabile, are currently used in the Bhutanese Traditional Medicine (BTM) for the management of different types of disorders including the diseases that bore relevance to various inflammatory conditions. Aims of the study: This study aimed to evaluate the inhibition of TNF-α production in LPS-activated THP-1 monocytic cells by the crude extracts of seven selected Bhutanese medicinal plants. It is expected to; (a) generate a scientific basis for their use in the BTM and (b) form a basis for prioritization of the seven plants for further phytochemical and anti-inflammatory studies. Materials and methods: Seven plants were selected using an ethno-directed bio-rational approach and their crude extracts were prepared using four different solvents (methanol, hexane, dichloromethane and chloroform). The TNF-α inhibitory activity of these extracts was determined by cytokine-specific sandwich quantitative enzyme-linked immunosorbent assays (ELISAs). The results were quantified statistically and the statistical significance were evaluated by GraphPad Prism version 5.01 using Student's t-test with one-tailed distribution. A p-value ≤0.05 was considered statistically significant. Results: Of the seven plants studied, the crude extracts of six of them inhibited the production of pro-inflammatory cytokine, TNF-α in LPS-activated THP-1 monocytic cells. Amongst the six plants, Corydalis crispa gave the best inhibitory activity followed by Pleurospermum amabile, Ajania nubigena, Corydalis dubia, Meconopsis simplicifolia and Codonopsis bhutanica. Of the 13 extracts that exhibited statistically significant TNF-α inhibitory activity (p<0.05; p<0.01), five of them showed very strong inhibition when compared to the DMSO control and RPMI media. Conclusions: Six medicinal plants studied here showed promising TNF-α inhibitory activity. These findings rationalize the traditional use of these selected medicinal plants in the BTM as an individual plant or in combination with other ingredients for the treatment of disorders bearing relevance to the inflammatory conditions. The results forms a good preliminary basis for the prioritization of candidate plant species for an in-depth phytochemical study and anti-inflammatory activity screening of the pure compounds contained within those seven plants. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: : This study involves the assessment of the Bhutanese traditional medicine (BTM) which was integrated with the mainstream biomedicine in 1967 to provide primary health care services in the country. It caters to 20–30% of the daily out-patients within 49 traditional medicine units attached to 20 district modern hospitals and 29 Basic Health Units in the country. Aim of the study: : This study presents the ethnopharmacological, ethnobotanical and the ethnoquality concepts in relation to mainstream Tibetan medicine and describes the current practices of BTM. Materials and methods: : Experienced BTM practitioners (Drung-tshos and Smen-pas) were selected using a convenience sampling method and were interviewed using an open questionnaire followed by informal discussions. The corpus of BTM, Tibetan and scientific literature was obtained and the information on ethnopharmacological, ethnoquality and ethnobotanical concepts and current practices of BTM was extracted. Results: : This study found that the BTM shares many similarities in terms of materia medica, pharmacopoeia and the principles and concepts of ethnopharmacology and ethnobotany with its mainstream Tibetan medicine. However, the resourceful Bhutanese Drung-tshos and Smen-pas have adapted this medical system based on the local language, culture, disease trend, health care needs and their familiarity with the locally available medicinal ingredients making it particular to the country. A number of notable distinctions observed in the current practices include a code of classification of diseases (only 79 of 404 types of disorders recognized), formulations (currently used only 103 of thousands formulation types), usage of medicinal plants (only 229 species of thousands described) and selected treatment procedures (golden needle and water therapy). This BTM was found to cater to 20–30% of daily out-patients visiting 49 modern hospitals and basic health units in the country. Conclusions: : The BTM has been evolved from the Tibetan medicine. While the pharmacopoeia, ethnopharmacology, ethnobotany and the ethnoquality aspects shares commonalities with the mainstream Tibetan medicine, there are some practices unique to BTM. Such uniqueness observed in the current practices of BTM include formulations, medicinal plants collection and usage, and the treatment procedures including golden needle and water therapy. This could be a promising source of information for the rediscovery of useful remedies, the development of modern phytotherapeutics and the establishment of efficient quality control measures. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: Corydalis dubia is used in Bhutanese traditional medicine as a febrifuge and for treating infections in the blood, liver and bile which correlate to the signs and symptoms of malarial and microbial infections. Aim of the study: To validate the ethnopharmacological uses of the plant and to discover potential new therapeutic drug leads. Materials and methods: C. dubia was collected from Bhutan and the alkaloids were obtained using acid–base fractionation and separation by repeated column and preparative plate chromatography. The alkaloids were identified from analysis of their physiochemical and spectroscopic data and were tested for antiplasmodial, antimicrobial and cytotoxicity activities. Results: A systematic extraction and isolation protocol yielded one new natural product, dubiamine, and seven known isoquinoline alkaloids, scoulerine, cheilanthifoline, protopine, capnoidine, bicuculline, corydecumbine and hydrastine. Among the four alkaloids tested, scoulerine showed the best antiplasmodial activity with IC50 values of 5.4μM and 3.1μM against the antifolate sensitive and the multidrug resistant P. falciparum strains: TM4/8.2 and K1CB1, respectively. None of the alkaloids tested showed significant antimicrobial or cytotoxicity activities. Conclusions: The antiplasmodial test results, of the isolated alkaloid components, are commensurated with the ethnopharmacological uses of this plant. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: As many as 229 medicinal plants have been currently used in the Bhutanese Traditional Medicine (BTM) as a chief ingredient of polyherbal formulations and these plants have been individually indicated for treating various types of infections including malaria, tumor, and microbial. We have focused our study only on seven species of these plants. Aim of the study: We aim to evaluate the antiplasmodial, antimicrobial, anti-Trypanosoma brucei rhodesiense and cytotoxicity activities of the seven medicinal plants of Bhutan selected using an ethno-directed bio-rational approach. This study creates a scientific basis for their use in the BTM and gives foundation for further phytochemical and biological evaluations which can result in the discovery of new drug lead compounds. Materials and methods: A three stage process was conducted which consisted of: (1) an assessment of a pharmacopoeia and a formulary book of the BTM for their mode of plant uses; (2) selecting 25 anti-infective medicinal plants based on the five established criteria, collecting them, and screening for their major classes of phytochemicals using appropriate test protocols; and (3) finally analyzing the crude extracts of the seven medicinal plants, using the standard test protocols, for their antiplasmodial, antimicrobial, anti-Trypanosoma brucei rhodesiense and cytotoxicity activities as directed by the ethnopharmacological uses of each plant. Results: Out of 25 medicinal plants screened for their major classes of phytochemicals, the majority contained tannins, alkaloids and flavonoids. Out of the seven plant species investigated for their biological activities, all seven of them exhibited mild antimicrobial properties, five plants gave significant in vitro antiplasmodial activities, two plants gave moderate anti-Trypanosoma brucei rhodesiense activity, and one plant showed mild cytotoxicity. Meconopsis simplicifolia showed the highest antiplasmodial activity with IC50 values of 0.40μg/ml against TM4/8.2 strain (a wild type chloroquine and antifolate sensitive strain) and 6.39μg/ml against K1CB1 (multidrug resistant strain) strain. Significantly the extracts from this plant did not show any cytotoxicity. Conclusions: These findings provide the scientific basis for the use of seven medicinal plants in the BTM for the treatment of malaria, microbial infections, infectious fevers, and the Trypanosoma brucei rhodesiense infection. The results also form a good preliminary basis for the prioritization of candidate plant species for further in-depth phytochemical and pharmacological investigations toward our quest to unearth lead antiparasitic, anticancer and antimicrobial compounds. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: The Bhutanese form of g.so-ba-rig-pa medicine, which is a scholarly medical system, belongs to a larger system of medicinal corpus that spreads from Mongolia to India. It uses medicinal plants as a bulk ingredient but only ‘Higher Elevation Medicinal Plants’ have been botanically identified so far. Our study reports the botanical identification of ‘Lower Elevation Medicinal Plants’ and their ethnomedical uses. Aim of the study: To botanically identify the ‘Lower Elevation Medicinal Plants’ used in Bhutanese traditional medicine. Materials and methods: A five stage process was conducted which consisted of: (1) a survey of specialized ancient ethnomedical literatures (Pharmacopoeias and formularies); (2) freely listing the ‘Lower Elevation Medicinal Plants’ reported in the ancient Bhutanese medical texts and translating their ethnomedical uses in equivalent terms of English; (3) making field visits, collecting herbarium specimens and photographs, and spot identification of plants; (4) double blind testing of Bhutanese traditional medicine practitioners for authentication and standardization of Bhutanese g.so-ba-rig-pa names; (5) organising workshops for open forum discussions on medicinal plants involving Traditional Physicians and other professional participants of the relevant areas. Results: We identified the botanical names of 113 ‘Lower Elevation Medicinal Plants’ belonging to 68 families and 104 genera. Out of 113 medicinal plant species identified, 92 species are currently used in Bhutan and the remaining 21 species were not used in the current formulation, but described in the Bhutanese traditional medical texts. The identification of these 21 species was achieved both ethnomedically and botanically for the first time. Out of the 28 plant species that are currently imported from India, we found for the first time, even to the knowledge of Traditional Physicians, that 16 of them are actually growing abundantly in Bhutan. Among the plant parts collected, seeds were the most prominent followed by fruits and then roots. Conclusions: Our study identified 113 ‘Lower Elevation Medicinal Plants’ out of which 92 of them are used daily in formulating 102 multi-ingredient prescription medicines in Bhutan. [Copyright &y& Elsevier]

Abstract Medicinal plants are used worldwide in primary health care and also for modern drug discovery programs. More than 13,000 species of Medicinal and Aromatic Plants are used in traditional medicines and herbal cosmetics throughout the world and about 8000 of these are used in South Asia alone. In Bhutan, while the total number of species used by Local Healing System(s) is unknown, more than 500 species of medicinal plants are recorded in the pharmacopoeia of Bhutanese traditional medicine called g.so-ba-rig-pa (Sowa Rigpa). Currently 300 species, which grow in diverse ecological zones of the country, are used by the Institute of Traditional Medicine Services in formulating 98 different essential Sowa Rigpa medicines. In 2007, 16 tons of medicinal plants were procured by the institute alone and 85% of them, almost all wild species, were collected within the country. Unless properly managed, the sustainability of these wild medicinal plants is likely to be threatened. In this light, our paper describes the possible risk factors that may affect the sustainable use of medicinal plants in Bhutan. Four broad risk factors, which include biological, ecological, social and economic issues, are identified here. Our paper also throws light to the current policies, frameworks and acts that are put in place to ensure the sustainable use of medicinal plants in Bhutan and finally suggests future directions. [ABSTRACT FROM AUTHOR]

Free listing and ranking techniques were used to acquire information on the medicinal plants, which grow exclusively in Bhutan, and to list the 15 most vulnerable species. Furthermore, the possible risk factors that may affect the sustainable use of medicinal plants were also identified. Self-administered, open questionnaires were answered and returned by 10 professionals who possess an extensive knowledge on medicinal plants used in the gso-ba-rig-pa system. A total number of 153 Medicinal and Aromatic Plants (MAPs) were listed. Almost 90% of these species are currently used by the Institute of Traditional Medicine Services (ITMS). All of the 15 most vulnerable species are high altitude medicinal herbs found in fragile ecosystems of the Himalayas between 3,000 to 5,500 meters above sea level. Among them, Meconopsis simplicifolia (D.Don), Walpers ranked first in its score and is considered the most threatened species. In the questionnaires, the respondents identified approximately 10 risk factors, which are related to the sustainable use of MAPs. These risk factors broadly fall into four categories: biological, ecological, social and economical factors. Current policies, frameworks and acts which are put in place to ensure the sustainable use of medicinal plants are described in this paper as well as a discussion on possible future directions. [ABSTRACT FROM AUTHOR]

Bhutan is a country blessed with many rich natural medicinal resources such as minerals, animals, plants, sman-chu (medicinal waters) and tshachu (hot springs). While minerals, animal parts and medicinal plants are used by the Institute of Traditional Medicine Services (ITMS) for compounding herbal medicines to provide health care services in Bhutan, tshachu are popularly used by the public as an alternative curative therapy for treating various diseases. Given such inherent health benefits that the tshachu reportedly have, the ITMS has carried out research on seven popular tshachu in Bhutan with a view to document, identify, validate and classify them according to the therapeutic properties described in the gSo-ba Rig-pa texts. Amongst all the seven tshachu studied, Kurtoe mKhem-pa lJong gNyes tshachu (in Lhuntshe-located in the north-east of Bhutan) was found to have profound religious, spiritual and historical significance, supported in many texts going back as far as the 8th century. It was reported that this tshachu was blessed by Guru Rimpoche and for the benefit of all sentient beings his manifestation Terton Pema Lingpa revealed it in the year 1475. Mainly for these reasons, it is considered the most sacred tshachu in Bhutan and people believe that it also cleanses one's defilements and sins. The literature reports the presence of nine related pools in the mKhem-pa lJong gNyes areas. However, only three pools in close proximity, called Guru tshachu, Tshe-dpag-med-tshachu and mKha'-'gro'i tshachu exist today. The users of this tshachu are mainly the people of Kurtoe, Kurman, Mongar, Tashigang, Tashi Yangtse and Bumthang. It is estimated that every year about twenty groups of at least 10 people each, visit this sacred tshachu. The study carried out by ITMS in 23rd January 2001 identified and established the main medicinal substances as well as the therapeutic properties of these three pools. The identification was based on their organoleptic properties. [ABSTRACT FROM AUTHOR]

• Quality control of Bhutanese herbal medicines is important for providing safe and effective treatments to the patients. • There is an urgent need to develop reliable analytical quality parameters to differentiate three Corydalis species. • Literature review revealed a comprehensive traditional and scientific information on three Corydalis species. • Six major quality parameters checklist for authenticating three Corydalis species has been identified and described. Herbal medicines including the scholarly Bhutanese Sowa Rigpa medicine (BSM) contribute significantly to primary health care services and play a considerable part in modern drug discovery. BSM, which was integrated with modern health care system in 1967, currently uses more than 200 species of medicinal plants including three closely related members of the Corydalis species; Corydalis calliantha , C. crispa , and C. dubia. Maintaining the quality of these medicinal plants has been always challenging due to adulterants and also due to lack of traditional quality control parameters that could distinguish closely related species. Therefore there is an urgent need to develop reliable analytical methods and quality parameters. Given the significant medicinal properties attributed to the three Corydalis species which are extensively used in BSM, a thorough literature review was performed to investigate their existing quality control parameters including: 1) morphological assessment, 2) habitat and ecological evaluation, 3) macroscopical and microscopical examination, 4) physiochemical limit setting and comparative high-performance thin layer chromatography (HPTLC) profiling, and 5) phytochemical and biological activities. The study revealed that there are distinct species-specific features including ecological adaptation, micromorphology, anatomy, phytochemical values and HPTLC profiles presented by each Corydalis species, and that these quality parameters support traditional quality screening processes in BSM. [ABSTRACT FROM AUTHOR]

This is an extensive review on epiphytic plants that have been used traditionally as medicines. It provides information on 185 epiphytes and their traditional medicinal uses, regions where Indigenous people use the plants, parts of the plants used as medicines and their preparation, and their reported phytochemical properties and pharmacological properties aligned with their traditional uses. These epiphytic medicinal plants are able to produce a range of secondary metabolites, including alkaloids, and a total of 842 phytochemicals have been identified to date. As many as 71 epiphytic medicinal plants were studied for their biological activities, showing promising pharmacological activities, including as anti-inflammatory, antimicrobial, and anticancer agents. There are several species that were not investigated for their activities and are worthy of exploration. These epipythes have the potential to furnish drug lead compounds, especially for treating cancers, and thus warrant indepth investigations. [ABSTRACT FROM AUTHOR]

Plant-derived compounds that modulate the immune responses are emerging as frontline treatment agents for cancer, infectious diseases and autoimmunity. Herein we have isolated 40 phytochemicals from five Bhutanese Sowa Rigpa medicinal plants—Aconitum laciniatum, Ajania nubegina, Corydalis crispa, Corydalis dubia and Pleurospermum amabile—and tested 14 purified compounds for their immunomodulatory properties using a murine dendritic cell (DC) line, and cytotoxicity against a human cholangiocyte cell line using xCELLigence real time cell monitoring. These compounds were: pseudaconitine, 14-veratryolpseudaconitine, 14-O-acetylneoline, linalool oxide acetate, (E)-spiroether, luteolin, luteolin-7-O-β-d-glucopyranoside, protopine, ochrobirine, scoulerine, capnoidine, isomyristicin, bergapten, and isoimperatorin. Of the 14 compounds tested here, scoulerine had adjuvant-like properties and strongly upregulated MHC-I gene and protein expression whereas bergapten displayed immunosuppressive properties and strongly down-regulated gene and protein expression of MHC-I and other co-stimulatory molecules. Both scoulerine and bergapten showed low cytotoxicity against normal healthy cells that were consistent with their immunoregulatory properties. These findings highlight the breadth of immunomodulatory properties of defined compounds from Bhutanese medicinal plants and show that some of these compounds exert their mechanisms of action by modulating DC activity. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Geological materials, such as minerals, have a long history of usage as ingredients in multicompound formulations of Himalayan Sowa Rigpa medicine – as well as in its localized form of Bhutanese traditional medicine (BTM) – for treating various disorders for over thousand years. Yet, hardly any scientific research has been done on their ethnopharmacological efficacy and chemistry. Aim of the study This study documents and correlates the rarely explored ethnopharmacological and chemical identification of various minerals and their ethnomedicinal uses in BTM formulations for the first time. Material and methods A five stage cross-disciplinary process was conducted as follows: (1) a review of classical literature of Sowa Rigpa texts (Tibetan medical texts, pharmacopoeias and formularies) that are still in use today; (2) listing of mineral ingredients according to Sowa Rigpa names, followed by identification with common English and chemical names, as well as re-translating their ethnomedical uses; (3) cross-checking the chemical names and chemical composition of identified Sowa Rigpa minerals with various geological mineral databases and mineral handbooks; (4) authentication and standardization of Sowa Rigpa names through open forum discussion with diverse BTM practitioners; (5) further confirmation of the chemical names of identified minerals by consulting different experts and pharmacognosists. Results Our current study lists 120 minerals as described in Sowa Rigpa medical textbooks most of which we were able to chemically identify, and of which 28 are currently used in BTM herbo-mineral formulations. Out of these 28 mineral ingredients, 5 originate from precious metal and stone, 10 stem from earth, mud and rocks, 8 are salts, and 5 concern ‘essences’ and exudates. Conclusions Our study identified 120 mineral ingredients described in Sowa Rigpa medical textbooks, out of which 28 are currently used. They are crucial in formulating 108 multicompound prescription medicines in BTM presently in use for treating more than 135 biomedically defined ailments. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance The traditional uses of Corydalis dubia, Ajania nubigena and Pleurospermum amabile in the Bhutanese traditional medicine for treating disorders related to inflammatory conditions and the in vitro anti-inflammatory activity of their crude extracts inspired the isolation and the investigation of anticolitic properties of four pure compounds. Materials and methods Three medicinal plants were collected from Himalayan Mountains of Bhutan. Capnoidine and scoulerine were isolated from C. dubia, linalool oxide acetate from A. nubigena and isomyristicin from P. amabile using natural product isolation protocols. Four compounds were investigated for their anti-inflammatory activities against IBD-colitis using chemically induced (TNBS) mice model of colitis. Capnoidine conferred the best preliminary protection against TNBS-induced colitis in mice and we have conducted in-depth pharmacological investigation of this compound including clinical symptoms, pathological signs, cytokine profiles, histological structure and inflammasomes using relevant bioassay protocols. Results Capnoidine-treated mice had significantly: a) improved clinical symptoms (body weight loss, mobility, piloerection and faecal consistency); b) reduced colon pathology (adhesion, oedema, ulceration, and colon length); c) altered inflammatory cytokines profiles within the colons; d) reduced levels of p-IκB-α (Ser32) and p-NF-κB p65 (Ser536) and e) reduced histological inflammation in the colon when compared with mice administered TNBS only. Conclusion Capnoidine presents as a potential new anti-inflammatory drug lead candidate for diseases where current standard-of-care often fails and is associated with major side effects. It also validates the traditional uses of C. dubia against inflammatory conditions and underlines the value of pursuing bioactive compounds derived from traditionally used ethnobotanical medicines. [ABSTRACT FROM AUTHOR]