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AbstractThere 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 cereusand Pseudomonas aeruginosa) but to show significant anti-legionellosis.

The floristic study along the Sherichhu River was carried out to determine the riparian plant species diversity and distribution pattern. A total of 34 study plots were laid on either side of the riverbank and recorded 72 woody species belonging to 52 families and 61 genera. Based on ocular inspections and topography, the areas were categorised into U-shaped and V-shaped valley. These two valleys, though differing in topography, has fostered the existence of diverse plant species in the study area. A considerable variation in the species diversity and richness was observed between the V-shaped and U-shaped regions based on the Shannon diversity index (P= 0.013) and species richness (P= 0.005) values. The Importance Value Indices (IVI) were highest for Desmodium elegans, Mallotus philippensis, and Rhus paniculatain the V-shaped area and Murraya koenigiiDuabanga grandifloraand Quercus glaucahad the highest IVI in the U-shaped area. Fabaceae, Euphorbiaceae, Anacardiaceae exhibited a high family value index (FVI) in the V-shaped area, while the U-shaped area had a high FVI for Rutaceaec, Lythraceae, Fagaceae, and Myrtaceae. Structurally, the Mallotus-Desmodium-Rhuscommunity was dominant in the V-shaped area, while Duabanga-Terminalia-Murrayaand Quercus-glaucawoodland communities were dominant in U-shaped valley. The CCA analysis revealed that the slope and litter thickness had shown greater influence on the plant species composition. In general, topography, micro-habitat conditions, river channel width, and flood regimes may have influenced riparian plant species diversity and distribution patterns. Thus, identifying key plant community types and underlying environmental conditions may help to accomplish and safeguard forest resources in the area. Riparian vegetation along the Sherichhu River is also a habitat for medicinal plants (11 out of 72 woody species), a source of food and income to rural communities. Thus, future studies should also focus on devising appropriate strategies for protecting and conserving Bhutan's riparian ecosystem from global warming.

AbstractLichen 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 cetrataAch and Parmelia dilatataVain inhibited Pseudomonas aeruginosa, most lichen extracts possessed moderate cytotoxicity. Cladonia scabriusculamethanol extract was cytotoxic against MCF7, Widr and Hela cell lines with IC50value of 324, 324, 476 μg/mL, respectively. Moreover, methanol extract of Physciacf. millegranaDegel indicated cytotoxicity against Hela cell line with IC50value 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.

AbstractNatural 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.

AbstractIn this study, 71 species of edible medicinal plants belonging to 49 families were identified. These medicinal plants (beside therapeutic applications in Sowa 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. leptocarpumand Podophyllum 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.

AbstractIn this work, total phenolic and flavonoid contents and antioxidant activities in methanol and aqueous extracts of five-high altitude medicinal plants namely Aconogonon tortuosum, Thlaspi arvense, Erysimum bhutanicum, Thalictrum chelidoniiand Aletris 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 of Thalictrum chelidoniiand methanol extract of Erysimum bhutanicumshowed best free radical scavenging activity. Both aqueous and methanol extracts of Aconogonon 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.

AbstractThe hydro-distillation of the dried aerial parts of Meconopsis 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.

Investigation of Aconitum orochryseum, a Bhutanese traditional medicine (“gSo-ba Rig-pa”) plant locally known as “Bong-kar”, resulted in the isolation of three new hetisine-type diterpenoid alkaloids, named orochrine ( 1), 2- O-acetylorochrine ( 2), and 2- O-acetyl-7α-hydroxyorochrine ( 3), together with the previously reported alkaloids atisinium chloride ( 4) and virescenine ( 5). The structures of the new alkaloids were elucidated by spectroscopic data analysis.

About half of the world’s population and 80% of the world’s biodiversity can be found in the tropics. Many diseases are specific to the tropics, with at least 41 diseases caused by endemic bacteria, viruses, parasites, and fungi. Such diseases are of increasing concern, as the geographic range of tropical diseases is expanding due to climate change, urbanization, change in agricultural practices, deforestation, and loss of biodiversity.

Iatrogenic hookworm therapy shows promise for treating disorders that result from a dysregulated immune system, including inflammatory bowel disease (IBD). Using a murine model of trinitrobenzenesulfonic acid-induced colitis and human peripheral blood mononuclear cells, we demonstrated that low-molecular-weight metabolites derived from both somatic extracts (LMWM-SE) and excretory-secretory products (LMWM-ESP) of the hookworm, Ancylostoma caninum, display anti-inflammatory properties.

Corydalisplants containing isoquinoline alkaloids are reported to possess promising pharmacological properties for the treatment of important diseases including cancer, inflammation, Alzheimer's disease and microbial infections. As part of a wider program investigating Bhutanese medicinal plants, we have previously identified eight isoquinoline alkaloids from C. dubia.Out of these, we report here on two of the major alkaloids, scoulerine (1) and cheilanthifoline (2) and their inhibitory activities against acetylcholinesterase (anti-AChE), tumor necrosis factor alpha (anti TNF-α) and a bacterial strain, Helicobacter pylori.Both alkaloids showed weak anti TNF-α and antibacterial activities. However, the anti-AChE activity of scoulerine (1) was promising as it significantly inhibited AChE with a minimum inhibitory requirement (MIR) value of 0.0015 nmol, which was two-fold better than the reference drug, galanthamine (MIR value of 0.003 nmol). As there are limited anti-Alzheimer's chemotherapeutics, scoulerine (1) is worthy of further exploration, including lead optimization, structure-activity-relationship studies, analog development, pharmacodynamics and in vivoanimal studies

With the objective of determining safety and verifying the traditional uses of the Bhutanese medicinal plant, Pleurospermum amabileCraib & W. W. Smith, we investigated its crude extracts and the isolated phytochemicals for their biological activities. Four phenylpropanoids [(E)-isomyristicin (1), (E)-isoapiol (2), methyl eugenol (3) and (E)-isoelemicin (4)] and six furanocoumarins [psoralen (5), bergapten (6), isoimperatorin (7), isopimpinellin (8), oxypeucedanin hydrate (9) and oxypeucedanin methanolate (10)] were isolated from this plant. Among the test samples, compound 10showed weak antibacterial activity against Bacillus subtilisand best antimalarial activity against the Plasmodium falciparumstrains, TM4/8.2 (chloroquine and antifolate sensitive) and K1CB1 (multidrug resistant). None of the test samples showed cytotoxicity. This study generated scientific data that support the traditional medical uses of the plant.

We have hydrodistilled the essential oil (EO) from the aerial parts of the Bhutanese medicinal plant, Pleurospermum amabileusing a Clevenger apparatus and evaluated this EO by GC/GC-MS and NMR analysis followed by testing for bioactivity. The GC-MS analysis identified 52 compounds with (E)-isomyristicin as a major component (32.2%). Repeated purification yielded four compounds; (E)-isomyristicin (1), (E)-isoapiol (2), methyl eugenol (3) and (E)-isoelemicin (4). Compound 2 and the mother EO showed the best antiplasmodial activity against the Plasmodium falciparumstrains, TM4/8.2 (chloroquine and antifolate sensitive) and K1CB1 (multidrug resistant). They exhibited mild antibacterial activity against Bacillus subtilis. None of the test samples showed cytotoxicity.

An investigation of the essential oil (EO) and the crude MeOH extract of a Bhutanese variety of Ajania nubigenausing GC/GC-MS and NMR found the following: a) one kg of the dried plant material contained 0.7% w/w EO; b) 44 of the 53 GC-FID peaks of the EO were identified with (3R,6R)-linalool oxide acetate (75.8 %) as the major constituent (chemotype II) and chamazulene as a new sub-chemotype; c) purification of the EO furnished (3R, 6R)-linalool oxide acetate (1), chamazulene (2), (E)-2-(2,4-hexadiynylidene)-1,6-dioxaspiro[4,4]non-3-ene (3), and (Z)-2-(2,4-hexadinylidene)-1,6-dioxaspiro[4,4]non-3-ene (4); d) from the crude MeOH extract, four flavonoid compounds: 1-(4-hydroxyphenyl)propan-1-one (5), oxyanin B (6), luteolin (7) (major) and the luteolin-7-O-β-D-glucoside (8) were isolated; e) among the EO and pure compounds tested for biological activities, compound 7exhibited a broad range of moderate antiplasmodial, cytoxicity and antimicrobial activities; c) compound 8showed significant in vitroantiplasmodial activity against P. falciparumstrains TM4/8.2 and K1CB1 (multidrug resistant strain) and was identified as a potential antimalarial scaffold; and f) the in vitroantimicrobial and cytotoxicity activities were in alignment with the traditional medical uses of this plant and thus substantiate its use in Bhutanese traditional medicine.

The chemical constituents and biological activities of Corydalis crispa(Fumariaceae) were investigated for the first time. The phytochemical study resulted in the isolation of nine known isoquinoline alkaloids: protopine (1), 13-oxoprotopine (2), 13-oxocryptopine (3), stylopine (4), coreximine (5), rheagenine (6), ochrobirine (7), sibiricine (8) and bicuculline (9), with complete NMR data for 2and 3provided here for the first time. Crude extracts exhibited significant anti-inflammatory (p<0.01) activity against TNF-αproduction in LPS activated THP-1 cells. The acetylcholinesterase inhibitory activity of compounds 2, 4and 7and the antiplasmodial activity of compound 5against P. falciparumstrains TM4/8.2 and K1CB1 (multidrug resistant strain) are reported here for the first time. Stylopine (4) did not show antimalarial activity against the K1CB1 strain in contrast to a previous report. This study generated a scientific basis for the use of this plant in Bhutanese traditional medicine, either individually or in combination with other medicinal ingredients to treat a broad range of disorders. This study also identified compound 5as potential new antimalarial lead compound.