莫罗尼苷与聚(ADP-核糖)聚合酶的相互作用可加强对阿脲诱导的遗传毒性和高血糖的代谢缓解作用:基于分子对接的体外和体内实验治疗见解。

IF 2.7 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Journal of Biomolecular Structure & Dynamics Pub Date : 2024-10-01 Epub Date: 2023-08-17 DOI:10.1080/07391102.2023.2246585
Sudatta Dey, Isha Nagpal, Priyanka Sow, Rishita Dey, Arnob Chakrovorty, Banani Bhattacharjee, Saikat Saha, Avishek Majumder, Manindranath Bera, Naidu Subbarao, Sisir Nandi, Sabir Hossen Molla, Pradeepta Guptaroy, Suresh K Abraham, Anisur Rahman Khuda-Bukhsh, Asmita Samadder
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引用次数: 0

摘要

本研究旨在评估具有生物活性的莫罗尼苷(MOR)在对抗阿脲(ALX)诱导的遗传毒性和高血糖症方面可能具有的潜力。硅学预测显示,MOR 与多(ADP-核糖)聚合酶(PARP)蛋白之间存在相互作用,这与体外 L6 细胞系和体内小鼠模型的实验结果相吻合。数据显示,MOR 可选择性地激活 PARP 蛋白,并调节其他应激蛋白 NF-κB 和 TNF-α,从而对 ALX 诱导的遗传毒性和高血糖产生保护作用。此外,通过 CD 光谱、UV-Vis 研究和 ITC 数据分析,MOR 与 CT-DNA(小牛胸腺 DNA)之间的强相互作用揭示了生物因子在抑制与 DNA 损伤相关的染色体畸变和微核形成方面的协同作用。最后,MOR 在抑制微生物生长方面没有发挥任何作用,而微生物生长抑制通常是由于高血糖菌群失调引起的。因此,从总体研究结果来看,我们可以得出结论,MOR可能是治疗诱导性高血糖和基因毒性的潜在候选药物。
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Morroniside interaction with poly (ADP-ribose) polymerase accentuates metabolic mitigation of alloxan-induced genotoxicity and hyperglycaemia: a molecular docking based in vitro and in vivo experimental therapeutic insight.

The present study tends to evaluate the possible potential of bio-active Morroniside (MOR), against alloxan (ALX)-induced genotoxicity and hyperglycaemia. In silico prediction revealed the interaction of MOR with Poly (ADP-ribose) polymerase (PARP) protein which corroborated well with experimental in vitro L6 cell line and in vivo mice models. Data revealed the efficacy of MOR in the selective activation of PARP protein and modulating other stress proteins NF-κB, and TNF-α to initiate protective potential against ALX-induced genotoxicity and hyperglycaemia. Further, the strong interaction of MOR with CT-DNA (calf thymus DNA) analyzed through CD spectroscopy, UV-Vis study and ITC data revealed the concerted action of bio-factors involved in inhibiting chromosomal aberration and micronucleus formation associated with DNA damage. Finally, MOR does not play any role in microbial growth inhibition which often occurs due to hyperglycemic dysbiosis. Thus, from the overall findings, we may conclude that MOR could be a potential drug candidate for the therapeutic management of induced-hyperglycaemia and genotoxicity.Communicated by Ramaswamy H. Sarma.

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来源期刊
Journal of Biomolecular Structure & Dynamics
Journal of Biomolecular Structure & Dynamics 生物-生化与分子生物学
CiteScore
8.90
自引率
9.10%
发文量
597
审稿时长
2 months
期刊介绍: The Journal of Biomolecular Structure and Dynamics welcomes manuscripts on biological structure, dynamics, interactions and expression. The Journal is one of the leading publications in high end computational science, atomic structural biology, bioinformatics, virtual drug design, genomics and biological networks.
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