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Yellow Himalayan Raspberry (Rubus ellipticus Sm.): Ethnomedicinal, Nutraceutical, and Pharmacological Aspects.
Lamichhane, A, Lamichhane, G, Devkota, HP
Molecules (Basel, Switzerland). 2023;(16)
Abstract
Yellow Himalayan raspberry (Rubus ellipticus Sm., Rosaceae) is a native species of the Indian subcontinent, Southern China, and the Philippines, which has been historically used as a traditional medicine and food. All of the parts of this plant have been used in traditional medicine to treat respiratory ailments, diabetes, and gastrointestinal disorder, and as an anti-infective agent. The scientific evaluation revealed a richness of macronutrients, micronutrients, and minerals in the fruits, indicating its potential use as a nutraceutical. Furthermore, this plant has been found to be rich in various secondary metabolites, including polyphenols, flavonoids, anthocyanins, tannins, and terpenoids. Ascorbic acid, kaempferol, gallic acid, and catechin are some of the compounds found in this plant, which have been widely discussed for their health benefits. Furthermore, various extracts and compounds obtained from R. ellipticus have shown antioxidant, antidiabetic, anticancer, anti-inflammatory, nephroprotective, antipyretic, anticonvulsant, and anti-infective activities investigated through different study models. These findings in the literature have validated some of the widespread uses of the fruits in folk medicinal systems and the consumption of this nutritious wild fruit by local communities. In conclusion, R. ellipticus holds strong potential for its development as a nutraceutical. It can also improve the nutritional status of villagers and uplift the economy if properly utilized and marketed.
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Bioactive Chemical Constituents and Pharmacological Activities of Ponciri Fructus.
Lamichhane, G, Pandey, J, Devkota, HP
Molecules (Basel, Switzerland). 2022;(1)
Abstract
Ponciri Fructus is a crude drug obtained from the dried immature fruits of Poncirus trifoliata (L). Raf. (Syn. Citrus trifoliata L.). This study aims to compile and analyze the ethnomedicinal uses, bioactive constituents, and pharmacological activities of Ponciri Fructus. Various online bibliographic databases namely, SciFinder, PubMed, Google Scholar, and Web of Science were used for collecting information on traditional uses, biological activities, and bioactive constituents. Concerning ethnomedicinal uses, Ponciri Fructus is extensively used in traditional Korean, Chinese, and Kampo medicines to mitigate allergic reactions, inflammation, edema, digestive complications, respiratory problems, spleen-related problems, liver complications, neuronal pain, hyperlipidemia, rheumatoid arthritis, cardiovascular problems, hernia, sinusitis, and insomnia. Several studies have shown that Ponciri Fructus is a major source of diverse classes of bioactive compounds namely flavonoids, terpenoids, coumarins, phytosterols, and alkaloids. Several in vivo and in vitro pharmacological activity evaluations such as antidiabetic, anti-obesity, anti-inflammatory, antiallergic, antimelanogenic, gastroprotective, anticancer, and neuroprotective effects have been conducted from Ponciri Fructus. However, scientific investigations focusing on bioassay-guided isolation and identification of specific bioactive constituents are limited. Therefore, an in-depth scientific investigation of Ponciri Fructus focusing on bioassay-guided isolation, mechanism based pharmacological studies, pharmacokinetic studies, and evaluation of possible toxicities is necessary in the future.
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Potential roles of medicinal plants for the treatment of viral diseases focusing on COVID-19: A review.
Adhikari, B, Marasini, BP, Rayamajhee, B, Bhattarai, BR, Lamichhane, G, Khadayat, K, Adhikari, A, Khanal, S, Parajuli, N
Phytotherapy research : PTR. 2021;(3):1298-1312
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Abstract
The whole world is entangled by the coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), people are dying in thousands each day, and without an actual medication, it seems not possible for the bringing this global health crisis to a stop. Natural products have been in constant use since ancient times and are proven by time to be effective. Crude extract or pure compounds isolated from medicinal plants and/or herbs such as Artemisia annua, Agastache rugosa, Astragalus membranaceus, Cassia alata, Ecklonia cava, Gymnema sylvestre, Glycyrrhizae uralensis, Houttuynia cordata, Lindera aggregata, Lycoris radiata, Mollugo cerviana, Polygonum multiflorum, Pyrrosia lingua, Saposhnikoviae divaricate, Tinospora cordifolia etc. have shown promising inhibitory effect against coronavirus. Several molecules, including acacetin, amentoflavone, allicin, blancoxanthone, curcumin, daidzein, diosmin, epigallocatechin-gallate, emodin, hesperidin, herbacetin, hirsutenone, iguesterin, jubanine G, kaempferol, lycorine, pectolinarin, phloroeckol, silvestrol, tanshinone I, taxifolin, rhoifolin, xanthoangelol E, zingerol etc. isolated from plants could also be potential drug candidates against COVID-19. Moreover, these could also show promising inhibitory effects against influenza-parainfluenza viruses, respiratory syncytial virus, severe acute respiratory syndrome (SARS), and Middle East respiratory syndrome coronavirus (MERS-CoV). Here, we have reported 93 antiviral drug candidates which could be a potential area of research in drug discovery.
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Potential natural inhibitors of xanthine oxidase and HMG-CoA reductase in cholesterol regulation: in silico analysis.
Marahatha, R, Basnet, S, Bhattarai, BR, Budhathoki, P, Aryal, B, Adhikari, B, Lamichhane, G, Poudel, DK, Parajuli, N
BMC complementary medicine and therapies. 2021;(1):1
Abstract
BACKGROUND Hypercholesterolemia has posed a serious threat of heart diseases and stroke worldwide. Xanthine oxidase (XO), the rate-limiting enzyme in uric acid biosynthesis, is regarded as the root of reactive oxygen species (ROS) that generate atherosclerosis and cholesterol crystals. β-Hydroxy β-methylglutaryl-coenzyme A reductase (HMGR) is a rate-limiting enzyme in cholesterol biosynthesis. Although some commercially available enzyme inhibiting drugs have effectively reduced cholesterol levels, most of them have failed to meet potential drug candidates' requirements. Here, we have carried out an in-silico analysis of secondary metabolites that have already shown good inhibitory activity against XO and HMGR in a wet lab setup. METHODS Out of 118 secondary metabolites reviewed, sixteen molecules inhibiting XO and HMGR were selected based on the IC50 values reported in in vitro assays. Further, receptor-based virtual screening was carried out against secondary metabolites using GOLD Protein-Ligand Docking Software, combined with subsequent post-docking, to study the binding affinities of ligands to the enzymes. In-silico ADMET analysis was carried out to explore their pharmacokinetic properties, followed by toxicity prediction through ProTox-II. RESULTS The molecular docking of amentoflavone (GOLD score 70.54, ∆G calc. = - 10.4 Kcal/mol) and ganomycin I (GOLD score 59.61, ∆G calc. = - 6.8 Kcal/mol) displayed that the drug has effectively bound at the competitive site of XO and HMGR, respectively. Besides, 6-paradol and selgin could be potential drug candidates inhibiting XO. Likewise, n-octadecanyl-O-α-D-glucopyranosyl (6' → 1″)-O-α-D-glucopyranoside could be potential drug candidates to maintain serum cholesterol. In-silico ADMET analysis has shown that these sixteen metabolites were optimal within the categorical range compared to commercially available XO and HMGR inhibitors, respectively. Toxicity analysis through ProTox-II revealed that 6-gingerol, ganoleucoin K, and ganoleucoin Z are toxic for human use. CONCLUSION This computational analysis supports earlier experimental evidence towards the inhibition of XO and HMGR by natural products. Further study is necessary to explore the clinical efficacy of these secondary molecules, which might be alternatives for the treatment of hypercholesterolemia.
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Pharmacologic activities of phytosteroids in inflammatory diseases: Mechanism of action and therapeutic potentials.
Marahatha, R, Gyawali, K, Sharma, K, Gyawali, N, Tandan, P, Adhikari, A, Timilsina, G, Bhattarai, S, Lamichhane, G, Acharya, A, et al
Phytotherapy research : PTR. 2021;(9):5103-5124
Abstract
Natural products and their derivatives are known to be useful for treating numerous diseases since ancient times. Because of their high therapeutic potentials, the use of different medicinal plants is possible to treat varied inflammation-mediated chronic diseases. Among natural products, phytosteroids have emerged as promising compounds mostly because they have diverse pharmacological activities. Currently, available medications exert numerous systemic toxicities, including hypertension, immune suppression, osteoporosis, and metabolic abnormalities. Thus, further research on phytosteroids to subside these complications is of significant importance. In this study, the information on phytosteroids, their types, and actions against inflammation, and allergic complications was collected by a systematic survey of literature on several scientific search engines. The literature review suggested that phytosteroids exhibit antiinflammatory action via different modes through transrepression or selective COX-2 enzymes. Also, in silico ADMET analysis was carried out on available phytosteroids to uncover their pharmacokinetic properties. Our analysis has shown that eight compounds: withaferin A, stigmasterol, β-sitosterol, guggulsterone, diosgenin, sarsasapogenin, physalin A, and dioscin, -isolated from medicinal plants show similar pharmacokinetic properties as compared to dexamethasone, commercially available glucocorticoid. These phytosteroids could be useful for the treatment of inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel diseases, multiple sclerosis, asthma, and cardiovascular diseases. Thus, systematic research is required to explore potent phytosteroids with lesser side effects, which might substitute the current medications.
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The catalytic role of water in the binding site of l,d-transpeptidase 2 within acylation mechanism: A QM/MM (ONIOM) modelling.
Ibeji, CU, Tolufashe, GF, Ntombela, T, Govender, T, Maguire, GEM, Lamichhane, G, Kruger, HG, Honarparvar, B
Tuberculosis (Edinburgh, Scotland). 2018;:222-230
Abstract
Mycobacterium tuberculosis is the causative agent of Tuberculosis. Formation of 3 → 3 crosslinks in the peptidoglycan layer of M. tuberculosis is catalyzed by l,d-transpeptidases. These enzymes can confer resistance against classical β-lactams that inhibit enzymes that generate 4 → 3 peptidoglycan crosslinks. The focus of this study is to investigate the catalytic role of water molecules in the acylation mechanism of the β-lactam ring within two models; 4- and 6-membered ring systems using two-layered our Own N-layer integrated Molecular Mechanics ONIOM (B3LYP/6-311++G(2d,2p): AMBER) model. The obtained thermochemical parameters revealed that the 6-membered ring model best describes the inhibition mechanism of acylation which indicates the role of water in the preference of 6-membered ring reaction pathway. This finding is in accordance with experimental data for the rate-limiting step of cysteine protease with the same class of inhibitor and binding affinity for both inhibitors. As expected, the ΔG# results also reveal that the 6-membered ring reaction pathway is the most favourable. The electrostatic potential (ESP) and the natural bond orbital analysis (NBO) showed stronger interactions in 6-membered ring transition state (TS-6) mechanism involving water in the active site of the enzyme. This study could be helpful in the development of novel antibiotics against l,d-transpeptidase.