Browsing by Author "Kumar, Rajnish"

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    Formulation and evaluation of SGLT2 inhibitory effect of a polyherbal mixture inspired from Ayurvedic system of medicine
    (National Taiwan University, 2022-03-22T00:00:00) Kumar, Ankit; Negi, Anoop Singh; Chauhan, Ashutosh; Semwal, Ravindra; Kumar, Rajnish; Semwal, Ruchi Badoni; Singh, Randhir; Joshi, Tushar; Chandra, Subhash; Joshi, Sunil Kumar; Semwal, Deepak Kumar
    Background and aim: The ingredients viz., Artemisia roxburghiana, Cissampelos pareira, Stephania glabra, Drimia indica, Roylea cinerea, Tinospora sinensis and Curcuma longa of the present formulation are used to treat diabetes in the Indian traditional medical system. Adopting the concept of multiple herbal mixtures for better therapeutic effects from the ancient Ayurvedic text Sarangdhar Samhita, the present study aimed to develop a polyherbal formulation (PHF) of seven herbs and to evaluate its sodium-glucose cotransporter protein-2 (SGLT2) inhibitory effect on type 2 diabetic rats. Experimental procedure: Streptozotocin (STZ) (60 mg/kg) and nicotinamide (NAM) (120 mg/kg) were intraperitoneally administered to induce type 2 diabetes in Wistar rats. The animals were divided into 5 groups viz. normal control, diabetic control, positive control (dapagliflozin at 0.1 mg/kg) and two test groups (PHF at 250 and 500 mg/kg). Various parameters including blood glucose, serum glutamic pyruvic transaminase (SGPT), serum glutamic-oxaloacetic transaminase (SGOT), bilirubin, triglycerides and creatinine were measured. Results and conclusion: The treatment with PHF (250 and 500 mg/kg) showed a significant (p < 0.05) decrease in blood glucose levels by 56.37% and 58.17%, respectively. The levels of SGOT, SGPT and bilirubin were significantly reduced in PHF-fed diabetic rats. Histopathological examination revealed no major changes in the treated groups as compared to the normal control. The molecular docking study showed strong binding of ?-sitosterol, insulanoline, warifteine, dehydrocorydalmine, taraxerol acetate, lupeol, corydalmine and luteolin to SGLT2 protein. The present study concludes that PHF has promising antidiabetic activity via inhibiting SGLT2 protein without showing any adverse effects. � 2022 Center for Food and Biomolecules, National Taiwan University
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    Virtual screening and molecular dynamics simulation approach for the identification of potential multi-target directed ligands for the treatment of Alzheimer�s disease
    (Taylor and Francis Ltd., 2023-04-28T00:00:00) Jangid, Kailash; Devi, Bharti; Sahoo, Ashrulochan; Kumar, Vijay; Dwivedi, Ashish Ranjan; Thareja, Suresh; Kumar, Rajnish; Kumar, Vinod
    Alzheimer�s disease (AD) is a multifactorial neurological disorder characterized by memory loss and cognitive impairment. The currently available single-targeting drugs have miserably failed in the treatment of AD, and multi-target directed ligands (MTDLs) are being explored as an alternative treatment strategy. Cholinesterase and monoamine oxidase enzymes are reported to play a crucial role in the pathology of AD, and multipotent ligands targeting these two enzymes simultaneously are under various phases of design and development. Recent studies have revealed that computational approaches are robust and trusted tools for identifying novel therapeutics. The current research work is focused on the development of potential multi-target directed ligands that simultaneously inhibit acetylcholinesterase (AChE) and monoamine oxidase B (MAO-B) enzymes employing a structure-based virtual screening (SBVS) approach. The ASINEX database was screened after applying pan assay interference and drug-likeness filter to identify novel molecules using three docking precision criteria; High Throughput Virtual Screening (HTVS), Standard Precision (SP), and Extra Precision (XP). Additionally, binding free energy calculations, ADME, and molecular dynamic simulations were employed to get structural insights into the mechanism of protein-ligand binding and pharmacokinetic properties. Three lead molecules viz. AOP19078710, BAS00314308 and BDD26909696 were successfully identified with binding scores of ?10.565, ?10.543 & ?8.066 kcal/mol against AChE and ?11.019, ?12.357 & ?10.068 kcal/mol against MAO-B, better score as compared to the standard inhibitors. In the near future, these molecules will be synthesized and evaluated through in�vitro and in�vivo assays for their inhibition potential against AChE and MAO-B enzymes. � 2023 Informa UK Limited, trading as Taylor & Francis Group.