Browsing by Author "Suresh Thareja"

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Anti-androgenic and anti-proliferative properties of methanolic leaf extract of Allamanda cathartica Linn. in adult mouse testis: Evidences from in vivo and in silico studies
(Elsevier Ltd, 2025) Rakesh Raman; Rimple Kaur; Swanand Kulkarni; Deepanshu Joshi; Jyoti Parkash; Suresh Thareja; Debarshi Sarkar; Shio Kumar Singh
Dysregulation in androgen production causes a variety of clinical disorders like male pattern baldness, hirsutism, acne vulgaris, benign prostatic hyperplasia, prostate cancer and polycystic ovarian syndrome. Although the common synthetic drugs used to treat these diseases have many side effects, there is growing demand for alternative and herbal therapies. Allamanda cathartica Linn. (family, Apocynaceae) is traditionally used to treat variety of diseases because of its hepatoprotective, antidiabetic, anti-inflammatory, antitumor and antimicrobial properties. However, the effects of Allamanda leaves on testosterone production still remain elusive. The present study aims to elucidate the effect and possible mode(s) of action of the methanolic leaf extract of A. cathartica (MLEAC) on androgen biosynthesis and germ cell proliferation in adult mouse testis. Adult male C57BL/6J mice were orally administered MLEAC (150 and 300 mg/kg body weight/day) or distilled water (controls) for 42 days. MLEAC treatment caused non-uniform degenerative changes in the histoarchitecture of testis. The treatment also had negative impact on serum testosterone level with downregulation of the expressions of major steroidogenic proteins (StAR, CYP11A1, 3β-and 17β-HSD3). Flow cytometry and immunohistochemical analyses showed impaired gem cell proliferation in MLEAC-treated mice testes. The GC-MS method identified 20 phytocompounds in MLEAC. The in silico study further revealed that GC-MS-derived phytochemicals have the potential to bind with major steroidogenic proteins in testis. MLEAC treatment thus causes suppression of germ cell proliferation via downregulation of testosterone production. Keeping in view the traditional use of Allamanda, the present findings may prove helpful in the search of a plant-based anti-androgenic compound. © 2025 Elsevier Ltd
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., 2024) Kailash Jangid; Bharti Devi; Ashrulochan Sahoo; Vijay Kumar; Ashish Ranjan Dwivedi; Suresh Thareja; Rajnish Kumar; Vinod Kumar
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.