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

Metabolomics and lipidomics studies of parasitic helminths: molecular diversity and identification levels achieved by using different characterisation tools

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

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

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

Immunomodulatory and biological properties of helminth-derived small molecules: Potential applications in diagnostics and therapeutics

Parasitic helminths secrete and excrete a vast array of molecules known to help skew or suppress the host’s immune response, thereby establishing a niche for sustained parasite maintenance. Indeed, the immunomodulatory potency of helminths is attributed mainly to excretory/secretory products (ESPs). The ESPs of helminths and the identified small molecules (SM) are reported to have diverse biological and pharmacological properties. The available literature reports only limited metabolites, and the identity of many metabolites remains unknown due to limitations in the identification protocols and helminth-specific compound libraries. Many metabolites are known to be involved in host-parasite interactions and pathogenicity. For example, fatty acids (e.g., stearic acid) detected in the infective stages of helminths are known to have a role in host interaction through facilitating successful penetration and migration inside the host. Moreover, excreted/secreted SM detected in helminth species are found to possess various biological properties, including anti-inflammatory activities, suggesting their potential in developing immunomodulatory drugs. For example, helminths-derived somatic tissue extracts and whole crude ESPs showed anti-inflammatory properties by inhibiting the secretion of proinflammatory cytokines from human peripheral blood mononuclear cells and suppressing the pathology in chemically-induced experimental mice model of colitis. Unlike bigger molecules like proteins, SM are ideal candidates for drug development since they are small structures, malleable, and lack immunogenicity. Future studies should strive toward identifying unknown SM and isolating the under-explored niche of helminth metabolites using the latest metabolomics technologies and associated software, which hold potential keys for finding new diagnostics and novel 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

Water-based therapies of Bhutan: current practices and the recorded clinical evidence of Balneotherapy

Medical water therapy (also called medical hydrology) is practiced worldwide both for relaxation and treatment of diseases. While this practice is still thriving in Bhutan, there is a lack of proper documentation and critical study. Therefore, the current study reports on the water therapies practiced in Bhutan and their health benefits. We used four-stage process: (1) a review of literature on balneotherapy (both traditional textbooks and scientific papers); (2) listing and surveying the hot springs, mineral, and holy spring waters; (3) reviewing the health records of the patients maintained at the traditional hospitals and interviewing traditional physicians and patients about health benefits; and (4) reviewing available literature to identify existing clinical trials data to provide evidence for hydrotherapies. We found three main forms of hydrotherapies are practiced in Bhutan, which comprises herbal bath therapy, balneotherapy, and spiritually empowered waters.The most popular hydrotherapies are herbal bath and hot spring therapies. Herbal bath therapy needs traditional physicians' prescriptions, while hot springs do not require it. Through field surveys, ten different hot springs (tsha-chu) and 17 medicinal water or mineral springs (sman-chu), and 17 holy spring-waters (sgrub-chu) were identified. In general, medical water therapies are used by the Bhutanese people to treat various ailments, including gastritis, neurological disorders, arthritis, dermatological diseases, and rheumatological and musculoskeletal disorders. Even though a lack of scientific evidence makes it difficult to draw concrete conclusions on their traditionally claimed efficacy and safety, there are clinical evidences documented from other countries

Antioxidant and Anti-Inflammatory Activities of Endemic Plants of the Australian Wet Tropics

Plants have been a vital source of natural antioxidants since ancient times. Plants growing under various abiotic stress conditions often produce more defensive secondary metabolites such as phenolics, flavonoids, and terpenoids during adaptation to the environment. Many of these secondary metabolites are known to possess antioxidant and anti-inflammatory properties. This study tested seven plants sourced from the mountaintop areas (above 1000 m elevation) of Mount Lewis National Park (falls under the Wet Tropics of Queensland), Australia, for their antioxidant and anti-inflammatory activities. Of the seven studied plants, hydroethanolic extracts of six plants (Leptospermum wooroonooran, Ceratopetalum hylandii, Linospadix apetiolatus, Garcinia brassii, Litsea granitica, and Polyscias willmottii) showed high 2,2-diphenyl-1-picrylhydrazyl (DPPH)-free radical scavenging activity in a dose-dependent (25–1000  g/mL) manner. At the highest concentration of 1 mg/mL, the DPPH free radical scavenged percentage varied between 75.4% and 92.3%. Only the species Alyxia orophila was inactive in the DPPH free radical scavenging assay. Pseudo-IC50 values of the extracts’ ferric reducing antioxidant power (FRAP) based on dose-response curves showed a significant positive correlation with total phenolic content. Five out of the seven plants, namely G. brassii, C. hylandii, L. apetiolatus, L. wooroonooran, and A. orophila, showed inhibitory effects on the secretion of proinflammatory cytokines, tumour necrosis factor (TNF), and interleukins (IL)-23 in a lipopolysaccharide (LPS)-stimulated human peripheral blood mononuclear cells (PBMCs) assay. The results of this study demonstrate the value of tropical mountaintop plants in the biodiscovery of antioxidant and anti-inflammatory lead compounds

Revisiting inflammatory bowel disease: pathology, treatments, challenges and emerging therapeutics including drug leads from natural products

Inflammatory bowel disease (IBD) is a chronic and life-long disease characterized by gastrointestinal tract inflammation. It is caused by the interplay of the host’s genetic predisposition and immune responses, and various environmental factors. Despite many treatment options, there is no cure for IBD. The increasing incidence and prevalence of IBD and lack of effective long-term treatment options have resulted in a substantial economic burden to the healthcare system worldwide. Biologics targeting inflammatory cytokines initiated a shift from symptomatic control towards objective treatment goals such as mucosal healing. There are seven monoclonal antibody therapies excluding their biosimilars approved by the US Food and Drug Administration for induction and maintenance of clinical remission in IBD. Adverse side effects associated with almost all currently available drugs, especially biologics, is the main challenge in IBD management. Natural products have significant potential as therapeutic agents with an increasing role in health care. Given that natural products display great structural diversity and are relatively easy to modify chemically, they represent ideal scaffolds upon which to generate novel therapeutics. This review focuses on the pathology, currently available treatment options for IBD and associated challenges, and the roles played by natural products in health care. It discusses these natural products within the current biodiscovery research agenda, including the applications of drug discovery techniques and the search for next-generation drugs to treat a plethora of inflammatory diseases, with a major focus on IBD

Metabolomes and lipidomes of the infective stages of the gastrointestinal nematodes, Nippostrongylus brasiliensis and Trichuris muris

Soil-transmitted helminths, including hookworms and whipworms, infect billions of people worldwide. Their capacity to penetrate and migrate through their hosts’ tissues is influenced by the suite of molecules produced by the infective developmental stages. To facilitate a better understanding of the immunobiology and pathogenicity of human hookworms and whipworms, we investigated the metabolomes of the infective stage of Nippostrongylus brasiliensis third-stage larvae (L3) which penetrate the skin and Trichuris muris eggs which are orally ingested, using untargeted liquid chromatography–mass spectrometry (LC-MS). We identified 55 polar metabolites through Metabolomics Standard Initiative level-1 (MSI-I) identification from N. brasiliensis and T. muris infective stages, out of which seven were unique to excretory/secretory products (ESPs) of N. brasiliensis L3. Amino acids were a principal constituent (33 amino acids). Additionally, we identified 350 putative lipids, out of which 28 (all known lipids) were unique to N. brasiliensis L3 somatic extract and four to T. muris embryonated egg somatic extract. Glycerophospholipids and glycerolipids were the major lipid groups. The catalogue of metabolites identified in this study shed light on the biology, and possible therapeutic and diagnostic targets for the treatment of these critical infectious pathogens. Moreover, with the growing body of literature on the therapeutic utility of helminth ESPs for treating inflammatory diseases, a role for metabolites is likely but has received little attention thus far