In-silico therapeutic investigations of arjunic acid and arjungenin as an FXR agonist and validation in 3T3-L1 adipocytes

T, Mohan Manu; Anand, T.; Kumar, P Bhuvanesh; Fathima, Asra; Khanum, Farhath

doi:10.1016/j.compbiolchem.2019.107163

Cited by 3 publications

(1 citation statement)

References 48 publications

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“…GW4064, the first nonsteroidal and selective agonist of FXR is studied to lower the free-fatty acid and triglyceride levels and is used as a structural template for identification of novel FXR agonists [ 34 ]. Recently, several in silico and in vitro experiments reported novel potential agonists of FXR through high-throughput screening [ 37–39 ]. For example, Grienke et al explored the agonistic potential of triterpenes in Ganoderma lucidum Karst.…”

Section: Introductionmentioning

confidence: 99%

Repurposing FDA-approved drugs as FXR agonists: a structure basedin silicopharmacological study

Jose

Devi²,

Sajeev

et al. 2023

Bioscience Reports

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Farnesoid X receptor (FXR) modulates the expression of genes involved in lipid and carbohydrate homeostasis and inflammatory processes. This nuclear receptor is likely a tumor suppressor in several cancers but its molecular mechanism of suppression is still under study. Several studies reported that FXR agonism increase the survival of colorectal, biliary tract and liver cancer patients. In addition, FXR expression was shown to be downregulated in many diseases such as obesity, irritable bowel syndrome, glomerular inflammation, diabetes, proteinuria and ulcerative colitis. Therefore, development of novel FXR agonists may have significant potential in the prevention and treatment of these diseases. In this scenario, computer-aided drug design procedures can be resourcefully applied for the rapid identification of promising drug candidates. In the present research study, we applied the molecular docking method in conjunction with molecular dynamics (MD) simulations to find out potential agonists for FXR based on structural similarity with the drug that is currently used as FXR agonist, obeticholic acid. Our results showed that alvimopan and montelukast could be used as potent FXR activators and outperform the binding affinity of obeticholic acid by forming stable conformation with the protein in silico. However, further investigational studies and validations of the selected drugs are essential to figure out their suitability for in vivo experiments and clinical trials.

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Section: Introductionmentioning

confidence: 99%

Repurposing FDA-approved drugs as FXR agonists: a structure basedin silicopharmacological study

Jose

Devi²,

Sajeev

et al. 2023

Bioscience Reports

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Development and validation of a high-performance thin-layer chromatography method for the simultaneous estimation of four cardioprotective triterpenoids in Terminalia arjuna W. & A. bark and a fermented polyherbal biomedicine

Haldar,

Ash,

Mohapatra

et al. 2023

JPC-J Planar Chromat

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Toxicological Evaluation and In Silico Identification of Acetylcholinesterase Inhibitors in a Commercial Polyherbal Formulation (KWAPF01)

Aladodo

Ibrahim

Sabiu

2022

Evidence-Based Complementary and Alternative Medicine

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This study investigated the toxicological implications of a commercial polyherbal formulation, KWAPF01. Twenty-four Wistar rats were randomized into six groups of four animals per group. The animals in Group 1 were administered placebo and designated as control, while the rats in Groups 2 to 6 were administered 1000, 1500, 2000, 2500, and 3000 mg/kg bodyweight single oral dose of KWAPF01, respectively, and subsequently monitored for gross morphological and behavioural changes for 72 h. Piloerection, reduced motility, and tremor were observed in experimental groups, and the median lethal dose (LD50) of the extract was 2225.94 mg/kg bodyweight. The 11 compounds identified through HPLC analysis of the extract were docked against acetylcholinesterase (AChE), and the docking scores ranged from −5.3 to −10.8 kcal/mol, with catechol (−5.3 kcal/mol) and berberine (−10.8 kcal/mol) having the highest and lowest binding energies, respectively. Judging by the results, it could be inferred that some of the constituents of KWAPF01 have a direct impact on the nervous system and this is possibly elicited via the cholinergic system as it contains a nicotinic acetylcholine receptors agonist and potential inhibitors of AChE. Therefore, the use of KWAPF01 needs to be cautiously guided.

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In-silico therapeutic investigations of arjunic acid and arjungenin as an FXR agonist and validation in 3T3-L1 adipocytes

Cited by 3 publications

References 48 publications

Repurposing FDA-approved drugs as FXR agonists: a structure basedin silicopharmacological study

Repurposing FDA-approved drugs as FXR agonists: a structure basedin silicopharmacological study

Development and validation of a high-performance thin-layer chromatography method for the simultaneous estimation of four cardioprotective triterpenoids in Terminalia arjuna W. & A. bark and a fermented polyherbal biomedicine

Toxicological Evaluation and In Silico Identification of Acetylcholinesterase Inhibitors in a Commercial Polyherbal Formulation (KWAPF01)

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