Search

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]

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]

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. [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]

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

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

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

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 μg/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. [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]

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]

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]

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: 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]

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: : 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 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]

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]