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The alkaloidal components of the Bhutanese medicinal plant Corydalis calliantha Long, which is used for the treatment of malaria, have been assessed. Four known alkaloids, protopine (1), scoulerine (2), cheilanthifoline (3) and stylopine (4) are reported from this plant for the first time. The protopine alkaloid, protopine, and the tetrahydroprotoberine alkaloid, cheilanthifoline, showed promising in vitro antiplasmodial activities against Plasmodium falciparum, both wild type (TM4) and multidrug resistant (K1) strains with IC50 values in the range of 2.78-4.29 µ m. Such activity had not been demonstrated previously for cheilanthifoline. The results thus support, at a molecular level, the clinical use of this plant in the Bhutanese traditional medicine and identified cheilanthifoline as a potential new antimalarial drug lead. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

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

Life without natural products is unimaginable. It has provided mankind with oxygen, water, fire, food, clothing, shelter and medicine. Its public health impact is considerably high, especially of traditional medicines and nature-based modern drugs. The traditional medicines, despite its limitations, are addressing the health needs of millions of people worldwide. It is estimated that about 65-85% of the world population uses traditional medicines for their primary health cares. It is also estimated that about 39% of all 520 new approved drugs in 1983-1994 were natural products and out of that 74% were discovered as a result of bio-prospecting from plants used in traditional medicines. Traditional medicines are increasingly getting more popular mainly because: a) it is holistic system with less side effects; b) it is evolving as an evidence-based medicine; c) its ethno-medical knowledge is applicable to modern drug discovery programs. As there are many diseases that cannot be cured by the existing drugs and as there are increasing cases of drug resistance, there is urgent need for drugs that are effective against these pathogens. Probably, traditional medicines could provide a solution in fighting them both as a health care delivery mechanism and as a means of chemotherapeutic pool. Bhutan is fortunate to be gifted with rich natural bio-diversity and rich traditional medical knowledge. The positive health impacts of the Bhutanese traditional medicines are resoundingly felt by Bhutanese. Besides, there is huge potential for bio-prospecting in Bhutan. This paper highlights world scenario on the health impacts of the: 1) natural product-based traditional medicines, 2) the natural product-based drug discoveries, and 3) Bhutanese traditional medicine and potential of bio-prospecting in Bhutan. [ABSTRACT FROM AUTHOR]

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

Dengue fever is one of the most common viral infections affecting humans. It is an expanding public health problem, particularly in tropical and subtropical regions. No effective vaccine or antiviral therapies against Dengue virus (DENV) infection are available. Therefore, there is a strong need to develop safe and effective therapeutic strategies that can reduce the burden and duration of hospitalizations due to this life-threatening disease. Oligonucleotide-based strategies are considered as an attractive means of inhibiting viral replication since oligonucleotides can be designed to interact with any viral RNA, provided its sequence is known. The resultant targeted destruction of viral RNA interferes with viral replication without inducing any adverse effects on cellular processes. In this review, we elaborate the ribozymes, RNA interference, CRISPR, aptamer and morpholino strategies for the inhibition of DENV replication and discuss the challenges involved in utilizing such approaches. [ABSTRACT FROM AUTHOR]

Epimutation by DNA Methyltransferase 1 (DNMT1), an epigenetic regulator enzyme, may lead to the proliferation of breast cancer. In this report, 168,686 natural products from the PubChem database were screened and modified by in silico method to acquire the potential inhibitor of DNMT1. The initial screening of PubChem natural products using Lipinski's and Veber's rules of three and toxic properties have resulted in 2601 fragment candidates. Four fragments from pharmacophore-based molecular docking simulation were modified by utilizing FragFP and the Lipinski's and Veber's rules of five, and resulted in 51,200 ligands. The toxicological screening collected 13,563 ligands for a series of pharmacophore-based molecular docking simulations to sort out the modified ligands, which had the better binding activity and interactions to DNMT1 compared to the standards, SAH, SAM, and SFG. This step resulted in five ligand candidates, namely C-7756, C-5769, C-1723, C-2129, and C-2140. The ADME-Tox properties prediction showed that the selected ligands are generally better than standards in terms of druglikeness, GI absorption, and oral bioavailability. C-7756 exhibited a stronger affinity to DNMT1 as well as better ADME-Tox properties compared to the other ligands. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Qin Pi (Fraxinus chinensis Roxb.) is commercially used in healthcare products for the improvement of intestinal function and gouty arthritis in many countries. Three new secoiridoid glucosides, (8E)-4′′-O-methylligstroside (1), (8E)-4′′-O-methyldemethylligstroside (2), and 3′′,4′′-di-O-methyl-demethyloleuropein (3), have been isolated from the stem bark of Fraxinus chinensis, together with 23 known compounds (4–26). The structures of the new compounds were established by spectroscopic analyses (1D, 2D NMR, IR, UV, and HRESIMS). Among the isolated compounds, (8E)-4′′-O-methylligstroside (1), (8E)-4′′-O-methyldemethylligstroside (2), 3′′,4′′-di-O-methyldemethyloleuropein (3), oleuropein (6), aesculetin (9), isoscopoletin (11), aesculetin dimethyl ester (12), fraxetin (14), tyrosol (21), 4-hydroxyphenethyl acetate (22), and (+)-pinoresinol (24) exhibited inhibition (IC50 ≤ 7.65 μg/mL) of superoxide anion generation by human neutrophils in response to formyl-L-methionyl-L-leuckyl-L-phenylalanine/cytochalasin B (fMLP/CB). Compounds 1, 9, 11, 14, 21, and 22 inhibited fMLP/CB-induced elastase release with IC50 ≤ 3.23 μg/mL. In addition, compounds 2, 9, 11, 14, and 21 showed potent inhibition with IC50 values ≤ 27.11 μM, against lipopolysaccharide (LPS)-induced nitric oxide (NO) generation. The well-known proinflammatory cytokines, tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6), were also inhibited by compounds 1, 9, and 14. Compounds 1, 9, and 14 displayed an anti-inflammatory effect against NO, TNF-α, and IL-6 through the inhibition of activation of MAPKs and IκBα in LPS-activated macrophages. In addition, compounds 1, 9, and 14 stimulated anti-inflammatory M2 phenotype by elevating the expression of arginase 1 and Krüppel-like factor 4 (KLF4). The above results suggested that compounds 1, 9, and 14 could be considered as potential compounds for further development of NO production-targeted anti-inflammatory agents. [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]

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.

Bhutan's scholarly traditional medical system is called Bhutanese Sowa Rigpa medicine (BSM). It was integrated with the modern healthcare system in 1967. Over 200 medicinal plants are used to produce more than 100 poly-ingredient medicinal formulations. Although BSM is supported by well-documented principles, pharmacopoeias, diagnostic procedures, treatment regimens, and traditional quality assurance systems, modern quality control parameters have become essential to distinguish closely related species and prevent contamination from exogenous impurities. This study aims to establish reliable analytical methods and quality control parameters for Aster flaccidus Bunge and Aster diplostephioides (DC.) Benth. ex C.B. Clarke used as ingredients in the BMS poly-ingredient medicinal formulations. Furthermore, their reported phytochemicals and biological activities are also discussed in this study. Standard pharmacognostic techniques, including macroscopical and microscopical examinations of crude drugs, were employed to establish the quality control parameters for two Aster species. The physicochemical limits were determined as per the World Health Organization (WHO)-recommended guidelines and methods described in the Thai herbal pharmacopoeia. A high-performance thin-layer liquid chromatography (HPTLC) was used to develop a comparative chromatogram/phytochemical fingerprint for the crude extracts obtained from two Aster species. A literature review was conducted to record their isolated phytochemicals and biological activities. Two Aster species possess macro- and microscopic features such as colour, appearance, and shape. Physicochemical analysis of crude drugs from two Aster species including HPTLC fingerprinting of their methanol crude extracts also yielded adequate data to differentiate and confirm two Aster species before adding them to the BSM poly-ingredient medicinal formulations. From the literature review, only A . flaccidus was found to be studied for its phytochemical constituents, whereby 11 pure compounds were isolated from aerial parts and roots. The current study revealed distinct species-specific distinguishing features, including ecological adaptation, micromorphology, anatomy, physicochemical values, HPTLC chromatograms. These parameters can be used to authenticate the species identity and prevent adulterations, thereby improving the quality and safety of BSM formulations., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

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., (© 2023. The Author(s).)

Background: Wound healing is an active, complex, integrated series of cellular, physiological, and biochemical changes initiated by the stimulus of injury in a tissue. The present study was performed to investigate the potential wound healing abilities of Sargassum ilicifolium crude extracts (CE) that were characterized by 1 H NMR and FTIR Spectrometric measurements., Materials and Methods: Seaweed samples were collected from southern coastal sites of Sri Lanka. To determine the cytotoxicity and proliferation of S. ilicifolium CE were used for the MTT and alamarBlue assays respectively. The scratch and exclusion wound models were used to HaCaT and HDF cells to assess the cell proliferation and migration. RAW 264.7 cells (macrophages) were used to evaluate Nitric Oxide (NO) production and phagocytosis activities. Moreover, Fifteen, 8-week-old, female, New Zealand rabbits were selected and divided into five groups: excision skin wounds (10.40 ± 0.60 mm) were induced in groups I, II, and III. Rabbits in groups I and IV were given S. ilicifolium CE (orally, 100 mg/kg day, two weeks), whereas groups II and V were given equal amounts of distilled water. Wound healing properties were measured and wound tissue samples were collated, formalin-fixed, wax-embedded, stained (Hematoxylin and Eosin; Van Gieson) and examined for the healing process., Results: Anti-inflammatory and wound healing activities were observed in RAW 264.7, HDF and HaCaT cells treated with S. ilicifolium aqueous extracts when compared to the control groups. S. ilicifolium extracts concentration 8 - 4 μg/μL, (P<0.05) had remarkable the highest proliferative and migratory effects on RAW 264.7, HDF and HaCaT cells when compared with the control. RAW 264.7 cell proliferation and/or migration were higher in S. ilicifolium extracts (4 μg/μL, 232.8 ± 10.07%) compared with the control (100 %). Scratch wound healing were remarkably enhanced in 24 h, 48 h (P<0.05) when treated with S. ilicifolium on HaCaT cells. Rabbits treated with the CE of S. ilicifolium showed a significantly increased wound healing activities (P<0.05) within three days with a close wound area of 57.21 ± 0.77 % compared with control group (26.63 ± 1.09 %). Histopathology, aspartate aminotransferase and alanine aminotransferase levels evidenced no toxic effects on seaweed treated groups. Histopathological results also revealed that the healing process was significantly faster in the rabbit groups which were as treated with CE of S. ilicifolium orally with the evidence of enhanced early granulation tissue (connective tissue and angiogenesis) and significant epithelization compared to the control., Conclusions: Cell proliferation and migration are significantly faster when treated with S. ilicifolium aqueous extracts. Moreover, there are no toxic effect of S. ilicifolium aqueous extracts on RAW 264.7, HDF and HaCaT cell lines. In this study, it is revealed that S. ilicifolium has potential remedial agent; D-Mannitol for skin wound healing properties that by promote keratinocyte and fibroblast proliferation and migration. These findings show that S. ilicifolium have promising wound healing properties., (© 2023. The Author(s).)

Traditional medicine in Bhutan is known as gSo-ba Rig-pa and is one of the oldest surviving medical traditions in the world. Other medical systems, such as Chinese medicine, Indian Ayurvedic medicine, Unani medicine, Greco-Roman medicine and the country's rich cultures and traditions have greatly influenced the way traditional Bhutanese medicine evolved. However, Buddhist philosophy remains the mainstream of this medical system. gSo-ba Rig-pa's principles are based on the perception the human body is composed of three main elements: rLung ('Air'), mKhris-pa ('Bile') and Bad-kan ('Phlegm'). When these three elements are balanced in the body a person is said to be healthy. The pathophysiology is also different from other medical systems, and the close link to Buddhism is reflected in the spiritual dimensions and the perception that all suffering is caused by ignorance. The treatment of diseases includes behavioral modification, physiotherapy, herbal medicines, minor surgery and spiritual healing. This makes the traditional Bhutanese medicine a unique and holistic health care system. The traditional medicine is an integrated and recognized part of the formal health care services in Bhutan under the auspices of the Ministry of Health. The article highlights three main points which can be learned from the Bhutanese experience: (1) the strong tradition of herbal medicines within gSo-ba Rig-pa forms a unique opportunity to prospect for new leads for development of pharmaceuticals, (2) the availability of the traditional medicine along with biomedicine broadens the health care choices for patients, and (3) the experiences of integrating two conceptually very different health care systems within one ministry contains important managerial lessons to be learned.