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Ulcerative colitis (UC) has no cure and no 'gold standard' diagnostic test, so there is an urgent need for effective diagnostic tools and treatments. More specific and non-invasive biomarkers that can diagnose UC early before the onset of clinical symptoms are required. Circulating microRNAs and exosomes have shown promise in monitoring disease activity and predicting flares without requiring invasive procedures. Recent trials of combined therapy using biologics or biologics combined with small-molecule drugs showed a significantly higher clinical response than monotherapy. Receptor inhibitors – for example, Janus kinases, interleukin 23 (IL23), and Smad7 – and fatty acid modulators are under current investigation and have the potential for clinical efficacy. Ulcerative colitis (UC) is one of the two forms of inflammatory bowel disease. It affects 5 million people globally, and is a chronic and recurring inflammation of the gastrointestinal tract with clinical presentation of abdominal pain, chronic diarrhea, rectal bleeding, and weight loss. The cause and the etiology of UC remain poorly understood. There is no cure and no 'gold standard diagnostic' for UC. The existing treatments are ineffective, and UC patients have a lower life expectancy with a risk of colorectal cancer. Recent studies in pathophysiology, clinical presentation, and biomarkers have significantly improved our understanding of UC. In this review we summarize recent advances in identifying novel clinical biomarkers, diagnostics, treatment targets, and emerging therapeutics. These insights are expected to assist in developing effective treatments for UC. [ABSTRACT FROM AUTHOR]

Simple Summary: Gastrointestinal parasites (GIPs) coevolved with mammalian hosts over millennia. These parasites produce small molecules, peptides, and proteins not only to evade or combat the host's immune response, but also to protect their host for longer coexistence. The emerging field of parasitomics uses various techniques, databases, and software associated with LC-MS (liquid chromatography–mass spectrometry), NMR (nuclear magnetic resonance), and other mass spectrometry platforms to study the polar and lipid molecules produced by GIPs. Recent advancements in AI-assisted tools and databases have significantly advanced this field, offering new insights into host–parasite interactions, immunomodulation and biochemical pathways. As research progresses, parasitomics promises to deepen our understanding of these complex relationships. Gastrointestinal parasites (GIPs) are organisms known to have coevolved for millennia with their mammalian hosts. These parasites produce small molecules, peptides, and proteins to evade or fight their hosts' immune systems and also to protect their host for their own survival/coexistence. The small molecules include polar compounds, amino acids, lipids, and carbohydrates. Metabolomics and lipidomics are emerging fields of research that have recently been applied to study helminth infections, host–parasite interactions and biochemicals of GIPs. This review comprehensively discusses metabolomics and lipidomics studies of the small molecules of GIPs, providing insights into the available tools and techniques, databases, and analytical software. Most metabolomics and lipidomics investigations employed LC-MS, MS or MS/MS, NMR, or a combination thereof. Recent advancements in artificial intelligence (AI)-assisted software tools and databases have propelled parasitomics forward, offering new avenues to explore host–parasite interactions, immunomodulation, and the intricacies of parasitism. As our understanding of AI technologies and their utilisation continue to expand, it promises to unveil novel perspectives and enrich the knowledge of these complex host–parasite relationships. [ABSTRACT FROM AUTHOR]

Introduction: Helminths are parasitic worms that infect millions of people worldwide and secrete a variety of excretory-secretory products (ESPs), including proteins, peptides, and small molecules. Despite this, there is currently no comprehensive review article on cataloging small molecules from helminths, particularly focusing on the different classes of metabolites (polar and lipid molecules) identified from the ESP and somatic tissue extracts of helminths that were studied in isolation from their hosts. Objective: This review aims to provide a comprehensive assessment of the metabolomics and lipidomics studies of parasitic helminths using all available analytical platforms. Method: To achieve this objective, we conducted a meta-analysis of the identification and characterization tools, metabolomics approaches, metabolomics standard initiative (MSI) levels, software, and databases commonly applied in helminth metabolomics studies published until November 2021. Result: This review analyzed 29 studies reporting the metabolomic assessment of ESPs and somatic tissue extracts of 17 helminth species grown under ex vivo/in vitro culture conditions. Of these 29 studies, 19 achieved the highest level of metabolite identification (MSI level-1), while the remaining studies reported MSI level-2 identification. Only 155 small molecule metabolites, including polar and lipids, were identified using MSI level-1 characterization protocols from various helminth species. Despite the significant advances made possible by the 'omics' technology, standardized software and helminth-specific metabolomics databases remain significant challenges in this field. Overall, this review highlights the potential for future studies to better understand the diverse range of small molecules that helminths produce and leverage their unique metabolomic features to develop novel treatment options. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is a chronic, lifelong disorder characterized by inflammation of the gastrointestinal (GI) tract. The exact etiology of IBD remains incompletely understood due to its multifaceted nature, which includes genetic predisposition, environmental factors, and host immune response dysfunction. Currently, there is no cure for IBD. This review discusses the available treatment options and the challenges they present. Importantly, we examine emerging therapeutics, such as biologics and immunomodulators, that offer targeted treatment strategies for IBD. While many IBD patients do not respond adequately to most biologics, recent clinical trials combining biologics with small-molecule drugs (SMDs) have provided new insights into improving the IBD treatment landscape. Furthermore, numerous novel and specific therapeutic targets have been identified. The high cost of IBD drugs poses a significant barrier to treatment, but this challenge may be alleviated with the development of more affordable biosimilars. Additionally, emerging point-of-care protein biomarkers from serum and plasma are showing potential for enhancing the precision of IBD diagnosis and prognosis. Several natural products (NPs), including crude extracts, small molecules, and peptides, have demonstrated promising anti-inflammatory activity in high-throughput screening (HTS) systems and advanced artificial intelligence (AI)-assisted platforms, such as molecular docking and ADMET prediction. These platforms are advancing the search for alternative IBD therapies derived from natural sources, potentially leading to more affordable and safer treatment options with fewer side effects. [ABSTRACT FROM AUTHOR]

Research is increasingly revealing that inflammation significantly contributes to various diseases, particularly inflammatory bowel disease (IBD). IBD is a major medical challenge due to its chronic nature, affecting at least one in a thousand individuals in many Western countries, with rising incidence in developing nations. Historically, indigenous people have used natural products to treat ailments, including IBD. Ethnobotanically guided studies have shown that plant-derived extracts and compounds effectively modulate immune responses and reduce inflammation. Similarly, helminths and their products offer unique mechanisms to modulate host immunity and alleviate inflammatory responses. This review explored the pharmaceutical potential of Aboriginal remedial plants and helminths for treating IBD, emphasizing recent advances in discovering anti-inflammatory small-molecule drug leads. The literature from Scopus, MEDLINE Ovid, PubMed, Google Scholar, and Web of Science was retrieved using keywords such as natural product, small molecule, cytokines, remedial plants, and helminths. This review identified 55 important Aboriginal medicinal plants and 9 helminth species that have been studied for their anti-inflammatory properties using animal models and in vitro cell assays. For example, curcumin, berberine, and triptolide, which have been isolated from plants; and the excretory-secretory products and their protein, which have been collected from helminths, have demonstrated anti-inflammatory activity with lower toxicity and fewer side effects. High-throughput screening, molecular docking, artificial intelligence, and machine learning have been engaged in compound identification, while clustered regularly interspaced short palindromic repeats (CRISPR) gene editing and RNA sequencing have been employed to understand molecular interactions and regulations. While there is potential for pharmaceutical application of Aboriginal medicinal plants and gastrointestinal parasites in treating IBD, there is an urgent need to qualify these plant and helminth therapies through reproducible clinical and mechanistic studies. [ABSTRACT FROM AUTHOR]

Natural products had been one of the important sources of remedial agents for thousands of years. From the data presented in this review, the utilization of biologically active natural products in traditional medicines and drug discoveries is still alive and well. This review presents the medicinal applications of natural products in both the traditional and modern medicines and shed lights on historical connections of this two medical system as well as identifies the potential sources of natural products that have been scantily explored till date. More than 85-90 % of the world populations rely on traditional medicines that use natural products, for their primary health services. Almost 73 % of the current pharmaceutical products/drugs are derived from natural products including medicinal agents from traditional medicines. These drugs are discovered from different sources including plants, animals and microbes. While plants had been the reliable sources of anticancer and antiparasitic drugs, microbial sources especially the Streptpmyces (actinomycetes) had been known for their antibiotic and anti-infective properties. More than 80-90 % of the world’s biodiversity including plants, marine world, animals, microbes and extremophiles remain under-explored for medicinal applications and merits our attention in near future. [ABSTRACT FROM AUTHOR]

We present evidence that the dog hookworm (Ancylostoma caninum) is underutilised in the study of host-parasite interactions, particularly as a proxy for the human-hookworm relationship. The inability to passage hookworms through all life stages in vitro means that adult stage hookworms have to be harvested from the gut of their definitive hosts for ex vivo research. This makes study of the human-hookworm interface difficult for technical and ethical reasons. The historical association of humans, dogs and hookworms presents a unique triad of positive evolutionary pressure to drive the A. caninum-canine interaction to reflect that of the human-hookworm relationship. Here we discuss A. caninum as a proxy for human hookworm infection and situate this hookworm model within the current research agenda, including the various 'omics' applications and the search for next generation biologics to treat a plethora of human diseases. Historically, the dog hookworm has been well described on a physiological and biochemical level, with an increasing understanding of its role as a human zoonosis. With its similarity to human hookworm, the recent publications of hookworm genomes and other omics databases, as well as the ready availability of these parasites for ex vivo culture, the dog hookworm presents itself as a valuable tool for discovery and translational research. [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]

The hydro-distillation of the dried aerial parts ofMeconopsis simplicifoliayielded essential oil (0.4 % v/w). The GC-FID coupled with GC-MS analysis detected at least 41 constituents of the chromatographable fraction of the total injected oil with bisabolene (29.2 %) as the major constituents of the oil. Strong antimalarial, moderate anti-inflammatory and weak antibacterial activities reported for the crude extracts and the alkaloids of this plant are also discussed. [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. [ABSTRACT FROM AUTHOR]

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]

Ethnopharmacological relevance: The plant Aconitum orochryseum Stapf. (Ranunculaceae) is employed together with other plants in Bhutanese traditional medicine and is indicated for malaria-associated fever. Aim of the study: To study the in vitro antiplasmodial activity of atisinium chloride, the major alkaloid from Aconitum orochryseum. Materials and methods: Atisinium chloride was extracted and purified from aerial parts of Aconitum orochryseum and its structure and absolute configuration confirmed by single crystal X-ray crystallography. The crude methanol extract, crude alkaloid fraction, and atisinium chloride were tested for in vitro antiplasmodial activity against the malarial Plasmodium falciparum strains TM4/8.2 (TM4; wild type) and K1CB1 (K1; chloroquine and antifolate resistant). Results: The diterpenoid alkaloid atisinium chloride was shown to have moderate antiplasmodial activities with IC50 values of 4μM and 3.6μM, respectively against the TM4 strain and the K1 strain of Plasmodium falciparum. Conclusions: Our studies provide the first evidence in support of one of the indicated treatments with Aconitum orochryseum in Bhutanese traditional medicine. This alkaloid also represents a potential new antimalarial structural lead. [Copyright &y& Elsevier]

Toxocariasis is a zoonotic disease affecting humans that is predominantly caused by Toxocara canis and T. cati, primarily parasites of dogs and cats, respectively. Toxocara generally establishes long-term infections by co-opting its host's physiological processes, while at the same time exploiting the nutritional environment. Adult stage T. canis reside in the gut of the definitive canine host where they employ a suite of strategies to combat intestinal immune responses by actively producing and releasing excretory-secretory products (ESPs). The protein component of T. canis ESPs has been widely studied, but characterisation of the non-protein ESP complement remains neglected. To characterize the secreted metabolome of Toxocara ESPs and to shed light on the parasite's metabolic processes, we profiled the ESPs of T. canis using both gas chromatography (GC) and liquid chromatography (LC) mass spectrometry approaches. We successfully identified 61 small molecules, including 41 polar metabolites, 14 medium-long chain fatty acids (MLCFAs) and six short chain fatty acids (SCFAs). We identified talose, stearic acid and isovalerate as the major compounds belonging to the polar, MLCFA and SCFA chemical classes, respectively. Most of the 61 identified metabolites appear to have been produced by T. canis via three distinct metabolic pathways - fatty acid, amino acid and carbohydrate metabolism. The majority of the identified ESPs have known biological properties, especially as immunomodulators. However, there is limited/no information on the biological roles or applications of 31 ESP biomolecules, suggesting that these may have novel activities that merit further investigation. [ABSTRACT FROM AUTHOR]

Recent studies have shown that seagrasses could possess potential applications in the treatment of inflammatory disorders. Five seagrass species (Zostera muelleri, Halodule uninervis, Cymodocea rotundata, Syringodium isoetifolium, and Thalassia hemprichii) from the Great Barrier Reef (QLD, Australia) were thus collected, and their preliminary antioxidant and anti-inflammatory activities were evaluated. From the acetone extracts of five seagrass species subjected to 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging antioxidant assay, the extract of Z. muelleri had the highest activity (half minimal concentration of inhibition (IC50) = 138 µg/mL), with the aerial parts (IC50 = 119 µg/mL) possessing significantly higher antioxidant activity than the roots (IC50 ≥ 500 µg/mL). A human peripheral blood mononuclear cells (PBMCs) assay with bacterial lipopolysaccharide (LPS) activation and LEGENDplex cytokine analysis showed that the aerial extract of Z. muelleri significantly reduced the levels of inflammatory cytokines tumour necrosis factor alpha (TNF-α), interleukin (IL)-1β, and IL-6 by 29%, 74%, and 90%, respectively, relative to the LPS treatment group. The aerial extract was thus fractionated with methanol (MeOH) and hexane fraction, and purification of the MeOH fraction by HPLC led to the isolation of 4-hydroxybenzoic acid (1), luteolin (2), and apigenin (3) as its major constituents. These compounds have been previously shown to reduce levels of TNF-α, IL-1β, and IL-6 and represent some of the major bioactive components of Z. muelleri aerial parts. This investigation represents the first study of the antioxidant and anti-inflammatory properties of Z. muelleri and the first isolation of small molecules from this species. These results highlight the potential for using seagrasses in treating inflammation and the need for further investigation. [ABSTRACT FROM AUTHOR]

Introduction: Soil-transmitted helminths infect billions of people, livestock and companion animals worldwide, and chronic infections with these nematodes represent a major health burden in many developing countries. On the other hand, complete elimination of parasitic helminths and other infectious pathogens has been implicated with rising rates of autoimmune and allergic disorders in developed countries. Given the enormous health impact of these parasites, it is surprising how little is known about the non-protein small metabolites of the excretory-secretory products (ESP), including their composition and pharmacological properties. Objectives: We sought proof-of-concept that Nippostrongylus brasiliensis and Trichuris muris, rodent models of two of the most important human soil-transmitted helminths, secrete small metabolites and that some of these metabolites may have specific pharmacological functions. Methods: N. brasiliensis and T. muris ESP were collected from adult worms and filtered using a 10 kDa cut-off membrane to produce excretory-secretory metabolites (ESM). The ESM were analysed using targeted gas chromatography–mass spectrometry and liquid chromatography–mass spectrometry for polar and non-polar small metabolites. Results: ESM from both N. brasiliensis and T. muris contained small molecules. A total of 54 small molecules (38 polar metabolites and 16 fatty acids) were identified, 36 known polar metabolites from N. brasiliensis and 35 from T. muris. A literature review of the identified compounds revealed that 17 of them have various demonstrated pharmacological activities. Conclusion: N. brasiliensis and T. muris secrete polar and non-polar small molecules with as many as 17 metabolites known to exhibit various pharmacological activities. [ABSTRACT FROM AUTHOR]

Parasitic helminths infect billions of people, livestock, and companion animals worldwide. Recently, they have been explored as a novel therapeutic modality to treat autoimmune diseases due to their potent immunoregulatory properties. While feeding in the gut/organs/tissues, the parasitic helminths actively release excretory-secretory products (ESP) to modify their environment and promote their survival. The ESP proteins of helminths have been widely studied. However, there are only limited studies characterizing the non-protein small molecule (SM) components of helminth ESP. In this study, using GC-MS and LC-MS, we have investigated the SM ESP of tapeworm Dipylidium caninum (isolated from dogs) which accidentally infects humans via ingestion of infected cat and dog fleas that harbor the larval stage of the parasite. From this D. caninum ESP, we have identified a total of 49 SM (35 polar metabolites and 14 fatty acids) belonging to 12 different chemotaxonomic groups including amino acids, amino sugars, amino acid lactams, organic acids, sugars, sugar alcohols, sugar phosphates, glycerophosphates, phosphate esters, disaccharides, fatty acids, and fatty acid derivatives. Succinic acid was the major small molecule present in the D. caninum ESP. Based on the literature and databases searches, we found that of 49 metabolites identified, only 12 possessed known bioactivities. [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]

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]

Tropospheric ozone (O3) is a global air pollutant that adversely affects plant growth. Whereas the impacts of O3 have previously been examined for some tropical commodity crops, no information is available for the pantropical crop, banana (Musa spp.). To address this, we exposed Australia's major banana cultivar, Williams, to a range of [O3] in open top chambers. In addition, we examined 46 diverse Musa lines growing in a common garden for variation in three traits that are hypothesised to shape responses to O3: (1) leaf mass per area; (2) intrinsic water use efficiency; and (3) total antioxidant capacity. We show that O3 exposure had a significant effect on the biomass of cv. Williams, with significant reductions in both pseudostem and sucker biomass with increasing [O3]. This was accompanied by a significant increase in total antioxidant capacity and phenolic concentrations in older, but not younger, leaves, indicating the importance of cumulative O3 exposure. Using the observed trait diversity, we projected O3 tolerance among the 46 Musa lines growing in the common garden. Of these, cv. Williams ranked as one of the most O3-tolerant cultivars. This suggests that other genetic lines could be even more susceptible, with implications for banana production and food security throughout the tropics. Tropospheric ozone (O3) is a global air pollutant that adversely affects plant growth and productivity. Whereas impacts of O3 have previously been examined in some commodity crops, no information is currently available for the pantropical staple crop, banana (Musa spp.). In this study, we have demonstrated the scale and possible prevalence of O3 susceptibility in bananas, with implications for production and food security throughout the tropics. [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]

Aconitum laciniatum is used in Bhutanese traditional medicine for treating various chronic infections and inflammatory conditions. We carried out in-depth isolation and characterization of the phytochemicals from the root component and determined the anti-inflammatory effects of the isolated compounds against chemically-induced colitis in mice. Five diterpenoid alkaloids - pseudaconitine, 14-veratroylpseudaconine, 14-O-acetylneoline, neoline, and senbusine A - were isolated from A. laciniatum for the first time. Two of the alkaloids were tested for anti-inflammatory properties in the TNBS-induced colitis model in mice. Various parameters were measured to assess pathology including weight loss, clinical and macroscopic scores, histological structure and IFN-γ production in the gut. Of the two alkaloids tested, 14-O-acetylneoline showed significant protection against different parameters of colitic inflammation. Compared to control mice that received TNBS alone, mice treated with 14-O-acetylneoline experienced significantly less weight loss and had significantly lower clinical scores, macroscopic pathology and grades of histological inflammation. Moreover, colonic IFN-γ mRNA levels were significantly reduced in mice that received 14-O-acetylneoline compared to control mice that received TNBS alone. This alkaloid is now considered a novel anti-colitis drug lead compound. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Seaweed is a popular edible source and is associated with many foods and pharmaceutical industries around the world. The current research aims to provide information on the chemical composition of 15 seaweed species, consisted of Chlorophyta, Ochrophyta/Phaeophyceae, and Rhodophyta macroalgae, collected from coastal areas of Sri Lanka. Seaweed samples were subjected to the analysis of lipids, proteins, ash and macro, micro, trace and ultra-trace elements. The highest protein content was recorded in the brown algae. Maximum dietary fiber and ash contents were recorded from green algae. The highest predominant fatty acids were observed from green seaweeds (Caulerparacemosa); however, linoleic acid (C18:2n6) is the dominant fatty acid of all macroalgae. Mineral contents were highest in the red macroalga; however, copper, zinc and magnesium were also comparatively higher in green alga Ulvalactuca. In conclusion, 15 seaweed species belonging to the three different classes of seaweeds are investigated in details to obtain their biochemical, mineral and fatty acid compositions for the synthesis of novel therapeutic agents. In order to explore biorefinery processes for these seaweeds, as well as how they can potentially be cultivated, more extensive studies are required. Studying and determining the nutritional values of seaweeds will be beneficial with the potentials for future industrial uses and research. [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]

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. [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]

There is an urgent need for novel drug leads, especially for microbial infections due to continuing emergence of drug resistance. Natural products are the backbone of modern medicine and the lichens have an important role to play in the discovery of novel drugs. Indonesia is gifted with a diverse array of lichens, which remain underexplored for medicinal applications. In this study, we have collected a lichen, Candelaria fibrosa, and conducted phytochemical and bioactivity studies. Using high performance liquid chromatography, mass spectrometry, and nuclear magnetic resonance spectroscopy, we have isolated and characterised two depside compounds, atraric acid (7) and methyl 3-hydroxy orsellinate (8). These two depsides were reported from this lichen species for the first time. The evaluation of the crude methanol extract against Gram-positive bacteria, Staphylococcus aureus, indicated insignificant activity. However, the isolated compounds have been previously reported to possess low antimicrobial activity against common pathogenic bacteria (Staphylococcus aureus, Bacillus cereus and Pseudomonas aeruginosa) but to show significant anti-legionellosis. [ABSTRACT FROM AUTHOR]

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. [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]

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. [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]

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. [Display omitted] • South Asia's natural product-based anthelmintic discovery is low-throughput. • Use of model nematodes can greatly increase the throughput of anthelmintic screens. • O. tipulae can be a suitable model nematode for anthelmintic screen in the tropics. • Creation of South Asia's first practical natural products library is warranted. • Pharmacologists and parasitologists should collaborate in anthelmintic discovery. [ABSTRACT FROM AUTHOR]

Lichen is a unique composite organism that arises from algae and fungi symbiotic relationship. There are 18,500 recorded lichen species worldwide but only limited number of global species has been tested for their biological activities. In particular, Indonesian lichens are rarely investigated. In this study, we collected and identified nine lichen species from six different locations in East Java Indonesia and screened their crude methanol extracts against gram-negative bacteria (Pseudomonas aeruginosa) and cancer cells (MCF7, Widr and Hela). While only the methanol extract of Parmelia cetrata Ach and Parmelia dilatata Vain inhibited Pseudomonas aeruginosa, most lichen extracts possessed moderate cytotoxicity. Cladonia scabriuscula methanol extract was cytotoxic against MCF7, Widr and Hela cell lines with IC50 value of 324, 324, 476 µg/mL, respectively. Moreover, methanol extract of Physcia cf. millegrana Degel indicated cytotoxicity against Hela cell line with IC50 value of 137 µg/mL. This study revealed anticancer potency of lichen of Java Island for the first time and further research is necessary for isolating the bioactive compounds. [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]

Background: Schistosomiasis affects over 200 million people and there are concerns whether the current chemotherapeutic control strategy (periodic mass drug administration with praziquantel (PZQ)—the only licenced anti-schistosome compound) is sustainable, necessitating the development of new drugs. Methodology/Principal findings: We investigated the anti-schistosome efficacy of polypyridylruthenium(II) complexes and showed they were active against all intra-mammalian stages of S. mansoni. Two compounds, Rubb12-tri and Rubb7-tnl, which were among the most potent in their ability to kill schistosomula and adult worms and inhibit egg hatching in vitro, were assessed for their efficacy in a mouse model of schistosomiasis using 5 consecutive daily i.v. doses of 2 mg/kg (Rubb12-tri) and 10 mg/kg (Rubb7-tnl). Mice treated with Rubb12-tri showed an average 42% reduction (P = 0.009), over two independent trials, in adult worm burden. Liver egg burdens were not significantly decreased in either drug-treated group but ova from both of these groups showed significant decreases in hatching ability (Rubb12-tri—68%, Rubb7-tnl—56%) and were significantly morphologically altered (Rubb12-tri—62% abnormal, Rubb7-tnl—35% abnormal). We hypothesize that the drugs exerted their activity, at least partially, through inhibition of both neuronal and tegumental acetylcholinesterases (AChEs), as worms treated in vitro showed significant decreases in activity of these enzymes. Further, treated parasites exhibited a significantly decreased ability to uptake glucose, significantly depleted glycogen stores and withered tubercules (a site of glycogen storage), implying drug-mediated interference in this nutrient acquisition pathway. Conclusions/Significance: Our data provide compelling evidence that ruthenium complexes are effective against all intra-mammalian stages of schistosomes, including schistosomula (refractory to PZQ) and eggs (agents of disease transmissibility). Further, the results of this study suggest that schistosome AChE is a target of ruthenium drugs, a finding that can inform modification of current compounds to identify analogues which are even more effective and selective against schistosomes. [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]