Climate-Affected Australian Tropical Montane Cloud Forest Plants: Metabolomic Profiles, Isolated Phytochemicals, and Bioactivities.

The Australian Wet Tropics World Heritage Area (WTWHA) in northeast Queensland is home to approximately 18 percent of the nation's total vascular plant species. Over the past century, human activity and industrial development have caused global climate changes, posing a severe and irreversible danger to the entire land-based ecosystem, and the WTWHA is no exception. The current average annual temperature of WTWHA in northeast Queensland is 24 °C. However, in the coming years (by 2030), the average annual temperature increase is estimated to be between 0.5 and 1.4 °C compared to the climate observed between 1986 and 2005. Looking further ahead to 2070, the anticipated temperature rise is projected to be between 1.0 and 3.2 °C, with the exact range depending on future emissions. We identified 84 plant species, endemic to tropical montane cloud forests (TMCF) within the WTWHA, which are already experiencing climate change threats. Some of these plants are used in herbal medicines. This study comprehensively reviewed the metabolomics studies conducted on these 84 plant species until now toward understanding their physiological and metabolomics responses to global climate change. This review also discusses the following: (i) recent developments in plant metabolomics studies that can be applied to study and better understand the interactions of wet tropics plants with climatic stress, (ii) medicinal plants and isolated phytochemicals with structural diversity, and (iii) reported biological activities of crude extracts and isolated compounds.

Approaches, Strategies and Procedures for Identifying Anti-Inflammatory Drug Lead Molecules from Natural Products.

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.

Development of quality control parameters for two Bhutanese medicinal plants (Aster flaccidus Bunge and Aster diplostephioides (DC.) Benth. ex C.B.Clarke) using traditional and modern pharmacognostical platforms.

Bhutan's scholarly traditional medical system is called Bhutanese Sowa Rigpa medicine (BSM). It was integrated with the modern healthcare system in 1967. Over 200 medicinal plants are used to produce more than 100 poly-ingredient medicinal formulations. Although BSM is supported by well-documented principles, pharmacopoeias, diagnostic procedures, treatment regimens, and traditional quality assurance systems, modern quality control parameters have become essential to distinguish closely related species and prevent contamination from exogenous impurities. This study aims to establish reliable analytical methods and quality control parameters for Aster flaccidus Bunge and Aster diplostephioides (DC.) Benth. ex C.B. Clarke used as ingredients in the BMS poly-ingredient medicinal formulations. Furthermore, their reported phytochemicals and biological activities are also discussed in this study. Standard pharmacognostic techniques, including macroscopical and microscopical examinations of crude drugs, were employed to establish the quality control parameters for two Aster species. The physicochemical limits were determined as per the World Health Organization (WHO)-recommended guidelines and methods described in the Thai herbal pharmacopoeia. A high-performance thin-layer liquid chromatography (HPTLC) was used to develop a comparative chromatogram/phytochemical fingerprint for the crude extracts obtained from two Aster species. A literature review was conducted to record their isolated phytochemicals and biological activities. Two Aster species possess macro- and microscopic features such as colour, appearance, and shape. Physicochemical analysis of crude drugs from two Aster species including HPTLC fingerprinting of their methanol crude extracts also yielded adequate data to differentiate and confirm two Aster species before adding them to the BSM poly-ingredient medicinal formulations. From the literature review, only A. flaccidus was found to be studied for its phytochemical constituents, whereby 11 pure compounds were isolated from aerial parts and roots. The current study revealed distinct species-specific distinguishing features, including ecological adaptation, micromorphology, anatomy, physicochemical values, HPTLC chromatograms. These parameters can be used to authenticate the species identity and prevent adulterations, thereby improving the quality and safety of BSM formulations.

The Ethnopharmacology, Phytochemistry and Bioactivities of the Corymbia Genus (Myrtaceae).

Plants have been vital to human survival for aeons, especially for their unique medicinal properties. Trees of the Eucalyptus genus are well known for their medicinal properties; however, little is known of the ethnopharmacology and bioactivities of their close relatives in the Corymbia genus. Given the current lack of widespread knowledge of the Corymbia genus, this review aims to provide the first summary of the ethnopharmacology, phytochemistry and bioactivities of this genus. The Scopus, Web of Science, PubMed and Google Scholar databases were searched to identify research articles on the biological activities, phytochemistry and ethnomedical uses of Corymbia species. Of the 115 Corymbia species known, 14 species were found to have ethnomedical uses for the leaves, kino and/or bark. Analysis of the references obtained for these 14 Corymbia spp. revealed that the essential oils, crude extracts and compounds isolated from these species possess an array of biological activities including anti-bacterial, anti-fungal, anti-protozoal, anti-viral, larvicidal, insecticidal, acaricidal, anti-inflammatory, anti-oxidant, anti-cancer and anti-diabetic activities, highlighting the potential for this under-studied genus to provide lead compounds and treatments for a host of medical conditions.

Phytochemical Content and Antidiabetic Properties of Most Commonly Used Antidiabetic Medicinal Plants of Kenya.

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.

Model nematodes as a practical innovation to promote high throughput screening of natural products for anthelmintics discovery in South Asia: Current challenges, proposed practical and conceptual solutions.

With the increasing prevalence of anthelmintic resistance in animals recorded globally, and the threat of resistance in human helminths, the need for novel anthelmintic drugs is greater than ever. Most research aimed at discovering novel anthelmintic leads relies on high throughput screening (HTS) of large libraries of synthetic small molecules in industrial and academic settings in developed countries, even though it is the tropical countries that are most plagued by helminth infections. Tropical countries, however, have the advantage of possessing a rich flora that may yield natural products (NP) with promising anthelmintic activity. Focusing on South Asia, which produces one of the world's highest research outputs in NP and NP-based anthelmintic discovery, we find that limited basic research and funding, a lack of awareness of the utility of model organisms, poor industry-academia partnerships and lack of technological innovations greatly limit anthelmintics research in the region. Here we propose that utilizing model organisms including the free-living nematode Caenorhabditis elegans, that can potentially allow rapid target identification of novel anthelmintics, and Oscheius tipulae, a closely related, free-living nematode which is found abundantly in soil in hotter temperatures, could be a much-needed innovation that can enable cost-effective and efficient HTS of NPs for discovering compounds with anthelmintic/antiparasitic potential in South Asia and other tropical regions that historically have devoted limited funding for such research. Additionally, increased collaborations at the national, regional and international level between parasitologists and pharmacologists/ethnobotanists, setting up government-industry-academia partnerships to fund academic research, creating a centralized, regional collection of plant extracts or purified NPs as a dereplication strategy and HTS library, and holding regional C. elegans/O. tipulae-based anthelmintics workshops and conferences to share knowledge and resources regarding model organisms may collectively promote and foster a NP-based anthelmintics landscape in South Asia and beyond.

Bioassay-Guided Isolation and Identification of Antiplasmodial Compounds from the Stem Bark of Clausena excavata.

Clausena excavata is a medicinal plant widely distributed in Southeast Asia. It is used for a variety of indications, including to treat malaria. In our present study, a phytochemical study of the methanol extract from the stem bark of C. excavata led to the isolation of five pyranocoumarins, nordentatin (1: ), dentatin (2: ), kinocoumarin (3: ), clausarin (4: ), and clausenidin (5: ), and a coumarin, 8-hydroxy-3″,4″-dihydrocapnolactone-2',3'-diol (6: ). The isolation of compound 6: from C. excavata and the antiplasmodial activities against a multidrug-resistant K1 strain of Plasmodium falciparum of 1, 3: , and 5: were reported for the first time. Compounds 3: and 4: exhibited potent antiplasmodial activities with EC50 values of 1.10 and 0.58 µM, respectively, while 1: and 5: had EC50 values of 5.62 and 7.15 µM, respectively. A prenyl group attached to the C-3 or C-12 position on the pyranocoumarin ring probably plays an important role on the activity. A hydroxyl group at the C-10 position is also likely to enhance the activity.

Phytochemistry and Pharmacology of Medicinal Plants Used by the Tenggerese Society in Java Island of Indonesia.

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.

Aboriginal medicinal plants of Queensland: ethnopharmacological uses, species diversity, and biodiscovery pathways.

BACKGROUND: Aboriginal peoples have occupied the island continent of Australia for millennia. Over 500 different clan groups or nations with distinctive cultures, beliefs, and languages have learnt to live sustainably and harmoniously with nature. They have developed an intimate and profound relationship with the environment, and their use of native plants in food and medicine is largely determined by the environment they lived in. Over 1511 plant species have been recorded as having been used medicinally in Australia. Most of these medicinal plants were recorded from the Aboriginal communities in Northern Territory, New South Wales, South Australia, and Western Australia. Not much has yet been reported on Aboriginal medicinal plants of Queensland. Therefore, the main aim of this review is to collect the literature on the medicinal plants used by Aboriginal peoples of Queensland and critically assess their ethnopharmacological uses. METHODS: The information used in this review was collected from archival material and uploaded into the Tropical Indigenous Ethnobotany Centre (TIEC) database. Archival material included botanist's journals/books and old hard copy books. Scientific names of the medicinal plant species were matched against the 'World Flora Online Plant List', and 'Australian Plant Census' for currently accepted species names to avoid repetition. An oral traditional medical knowledge obtained through interviewing traditional knowledge holders (entered in the TIEC database) has not been captured in this review to protect their knowledge. RESULTS: This review identified 135 species of Queensland Aboriginal medicinal plants, which belong to 103 genera from 53 families, with Myrtaceae being the highest represented plant family. While trees represented the biggest habit, leaves were the most commonly used plant parts. Of 62 different diseases treated by the medicinal plants, highest number of plants are used for treating skin sores and infections. Few plants identified through this review can be found in other tropical countries but many of these medicinal plants are native to Australia. Many of these medicinal plants are also used as bush food by Aboriginal peoples. CONCLUSION: Through extensive literature review, we found that 135 medicinal plants native to Queensland are used for treating 62 different diseases, especially skin infections. Since these medicinal plants are also used as bush food and are rarely studied using the Western scientific protocols, there is a huge potential for bioprospecting and bush food industry.

Indigenous Uses, Phytochemical Analysis, and Anti-Inflammatory Properties of Australian Tropical Medicinal Plants.

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.

Plant Secondary Metabolites Produced in Response to Abiotic Stresses Has Potential Application in Pharmaceutical Product Development.

Plant secondary metabolites (PSMs) are vital for human health and constitute the skeletal framework of many pharmaceutical drugs. Indeed, more than 25% of the existing drugs belong to PSMs. One of the continuing challenges for drug discovery and pharmaceutical industries is gaining access to natural products, including medicinal plants. This bottleneck is heightened for endangered species prohibited for large sample collection, even if they show biological hits. While cultivating the pharmaceutically interesting plant species may be a solution, it is not always possible to grow the organism outside its natural habitat. Plants affected by abiotic stress present a potential alternative source for drug discovery. In order to overcome abiotic environmental stressors, plants may mount a defense response by producing a diversity of PSMs to avoid cells and tissue damage. Plants either synthesize new chemicals or increase the concentration (in most instances) of existing chemicals, including the prominent bioactive lead compounds morphine, camptothecin, catharanthine, epicatechin-3-gallate (EGCG), quercetin, resveratrol, and kaempferol. Most PSMs produced under various abiotic stress conditions are plant defense chemicals and are functionally anti-inflammatory and antioxidative. The major PSM groups are terpenoids, followed by alkaloids and phenolic compounds. We have searched the literature on plants affected by abiotic stress (primarily studied in the simulated growth conditions) and their PSMs (including pharmacological activities) from PubMed, Scopus, MEDLINE Ovid, Google Scholar, Databases, and journal websites. We used search keywords: "stress-affected plants," "plant secondary metabolites, "abiotic stress," "climatic influence," "pharmacological activities," "bioactive compounds," "drug discovery," and "medicinal plants" and retrieved published literature between 1973 to 2021. This review provides an overview of variation in bioactive phytochemical production in plants under various abiotic stress and their potential in the biodiscovery of therapeutic drugs. We excluded studies on the effects of biotic stress on PSMs.

Vascular Epiphytic Medicinal Plants as Sources of Therapeutic Agents: Their Ethnopharmacological Uses, Chemical Composition, and Biological Activities.

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.

Anti-Infective and Anti-Cancer Properties of the Annona Species: Their Ethnomedicinal Uses, Alkaloid Diversity, and Pharmacological Activities.

Annona species have been a valuable source of anti-infective and anticancer agents. However, only limited evaluations of their alkaloids have been carried out. This review collates and evaluates the biological data from extracts and purified isolates for their anti-infective and anti-cancer activities. An isoquinoline backbone is a major structural alkaloid moiety of the Annona genus, and more than 83 alkaloids have been isolated from this genus alone. Crude extracts of Annona genus are reported with moderate activities against Plasmodium falciparum showing larvicidal activities. However, no pure compounds from the Annona genus were tested against the parasite. The methanol extract of Annona muricata showed apparent antimicrobial activities. The isolated alkaloids from this genus including liriodenine, anonaine, asimilobine showed sensitivity against Staphylococcus epidermidis. Other alkaloids such as (+)-Xylopine and isocoreximine indicated significant anti-cancer activity against A549 and K-562 cell lines, respectively. This review revealed that the alkaloids from Annona genus are rich in structural diversity and pharmacological activities. Further exploration of this genus and their alkaloids has potential for developing novel anti-infective and anticancer drugs.

Hookworm-Derived Metabolites Suppress Pathology in a Mouse Model of Colitis and Inhibit Secretion of Key Inflammatory Cytokines in Primary Human Leukocytes.

Iatrogenic hookworm therapy shows promise for treating disorders that result from a dysregulated immune system, including inflammatory bowel disease (IBD). Using a murine model of trinitrobenzenesulfonic acid-induced colitis and human peripheral blood mononuclear cells, we demonstrated that low-molecular-weight metabolites derived from both somatic extracts (LMWM-SE) and excretory-secretory products (LMWM-ESP) of the hookworm, Ancylostoma caninum, display anti-inflammatory properties. Administration to mice of LMWM-ESP as well as sequentially extracted fractions of LMWM-SE using both methanol (SE-MeOH) and hexane-dichloromethane-acetonitrile (SE-HDA) resulted in significant protection against T cell-mediated immunopathology, clinical signs of colitis, and impaired histological colon architecture. To assess bioactivity in human cells, we stimulated primary human leukocytes with lipopolysaccharide in the presence of hookworm extracts and showed that SE-HDA suppressed ex vivo production of inflammatory cytokines. Gas chromatography-mass spectrometry (MS) and liquid chromatography-MS analyses revealed the presence of 46 polar metabolites, 22 fatty acids, and five short-chain fatty acids (SCFAs) in the LMWM-SE fraction and 29 polar metabolites, 13 fatty acids, and six SCFAs in the LMWM-ESP fraction. Several of these small metabolites, notably the SCFAs, have been previously reported to have anti-inflammatory properties in various disease settings, including IBD. This is the first report showing that hookworms secrete small molecules with both ex vivo and in vivo anti-inflammatory bioactivity, and this warrants further exploration as a novel approach to the development of anti-inflammatory drugs inspired by coevolution of gut-dwelling hookworms with their vertebrate hosts.

Defined Small Molecules Produced by Himalayan Medicinal Plants Display Immunomodulatory Properties.

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-ß-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.

Geopharmaceuticals of Himalayan Sowa Rigpa medicine: Ethnopharmacological uses, mineral diversity, chemical identification and current utilization in Bhutan.

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.

A medicinal plant compound, capnoidine, prevents the onset of inflammation in a mouse model of colitis.

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.

Animal-derived natural products of Sowa Rigpa medicine: Their pharmacopoeial description, current utilization and zoological identification.

ETHNOPHARMACOLOGICAL RELEVANCE: The Bhutanese Sowa Rigpa medicine (BSM) uses animal parts in the preparation of numerous polyingredient traditional remedies. Our study reports the taxonomical identification of medicinal animals and the description of traditional uses in English medical terminologies. AIM OF THE STUDY: To taxonomically identify the medicinal animals and their derived natural products used as a zootherapeutic agents in BSM. MATERIALS AND METHODS: First, the traditional textbooks were reviewed to generate a list of animal products described as ingredients. Second, animal parts that are currently used in Bhutan were identified. Third, the ethnopharmacological uses of each animal ingredients were translated into English medical terminologies by consulting Traditional Physicians, clinical assistants, pharmacognosists, and pharmacists in Bhutan. Fourth, the animal parts were taxonomically identified and their Latin names were confirmed by crosschecking them with online animal databases and relevant scientific literature. RESULTS: The study found 73 natural products belonging to 29 categories derived from 45 medicinal animals (36 vertebrates and 9 invertebrates), comprising of 9 taxonomic categories and 30 zoological families. Out of 116 formulations currently produced, 87 of them contain one or more extracts and products obtained from 13 medicinal animals to treat more than 124 traditionally classified illnesses. Only five animal ingredients were found available in Bhutan and rest of the animal parts are being imported from India. CONCLUSIONS: Out of 73 natural products described in the traditional textbooks, only 13 of them (some omitted and few substituted by plants) are currently included in 87 formulations of BSM.

Pharmacological, ethnopharmacological, and botanical evaluation of subtropical medicinal plants of Lower Kheng region in Bhutan.

BACKGROUND: The Bhutanese Sowa Rigpa medicine (BSM) uses medicinal plants as the bulk ingredients. Our study was to botanically identify subtropical medicinal plants from the Lower Kheng region in Bhutan, transcribe ethnopharmacological uses, and highlight reported pharmacological activities of each plant. METHODS: We freely listed the medicinal plants used in the BSM literature, current formulations, and the medicinal plants inventory documents. This was followed by a survey and the identification of medicinal plants in the Lower Kheng region. The botanical identification of each medicinal plant was confirmed using The Plant List, eFloras, and TROPICOS. Data mining for reported pharmacological activities was performed using Google Scholar, Scopus, PubMed, and SciFinder Scholar. RESULTS: We identified 61 subtropical plants as the medicinal plants used in BSM. Of these, 17 plants were cultivated as edible plant species, 30 species grow abundantly, 24 species grow in moderate numbers, and only seven species were scarce to find. All these species grow within the altitude range of 100-1800 m above sea level. A total of 19 species were trees, and 13 of them were shrubs. Seeds ranked first in the parts usage category. Goshing Gewog (Block) hosted maximum number of medicinal plants. About 52 species have been pharmacologically studied and only nine species remain unstudied. CONCLUSION: Lower Kheng region is rich in subtropical medicinal plants and 30 species present immediate economic potential that could benefit BSM, Lower Kheng communities and other Sowa Rigpa practicing organizations.

Quality assurance of the university medical education, hospital services and traditional pharmaceutical products of the Bhutanese So-wa-rig-pa health care system.

BACKGROUND: The Bhutanese So-wa-rig-pa medicine (BSM) was integrated with the allopathic (modern) health care system in 1967. Ever since the health care integration policy was implemented, the BSM has gone through many phases of quality improvement and changes including the establishment of one university-based institute, 58 hospitals and Basic Health Units (BHU)-based health care services, and one traditional medicine factory. The BSM provides primary health care services to more than 20-30 % of patients who visit hospitals and BHU on a daily basis. However, there has been no study covering the quality assurance system of BSM. Our paper addresses this information gap. METHODS: This study was an observational ethnographic study supported by phenomenological understanding and content analysis of the data. The information was triangulated through consultation with the BSM practitioners (discussion (N = 8)) and personalized in-depth question-answer sessions using electronic protocols (N = 5). These participants comprised BSM educationists, clinical physicians, researchers, production and the quality assurance staff who were selected using convenience and purposive sampling method. The relevant So-wa-rig-pa information and literature were obtained from the government policy documents, official websites, scientific papers and the traditional medical texts. This study is enhanced by our practical observations and first-hand experience with BSM while working as the researchers at the Ministry of Health in Bhutan. In addition, the information in this paper is crosschecked and authenticated by five So-wa-rig-pa practitioners of Bhutan. RESULTS: The study highlights the following: a) The BSM receives both the government and people's support, b) The quality assurance system have been developed by integrating the traditional empirical knowledge and modern scientific protocols, c) There exist three administrative and functional organizations responsible for providing the quality BSM health care services in Bhutan, d) Extensive standard treatment guidelines and Quality documentation system exist for BSM as required by the regulatory bodies in Bhutan. The paper also recommends appropriate future directions for BSM. CONCLUSIONS: The BSM plays significant role in the primary health care system of the country. Consequently, the quality, safety and efficacy of BSM has been given priority by the Bhutan government. Many scientific protocols were integrated with the traditional quality approaches and further scientific studies are still required to improve its quality.