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莫诺苷与聚(ADP-核糖)聚合酶相互作用可增强三氧嘧啶诱导的遗传毒性和高血糖症的代谢缓解作用:基于分子对接和实验治疗的见解。

Morroniside interaction with poly (ADP-ribose) polymerase accentuates metabolic mitigation of alloxan-induced genotoxicity and hyperglycaemia: a molecular docking based and experimental therapeutic insight.

机构信息

Cytogenetics and Molecular Biology Laboratory, Department of Zoology, University of Kalyani, Kalyani, Nadia, India.

Dum Dum Motijheel College, Kolkata, India.

出版信息

J Biomol Struct Dyn. 2024 Oct;42(16):8541-8558. doi: 10.1080/07391102.2023.2246585. Epub 2023 Aug 17.

DOI:10.1080/07391102.2023.2246585
PMID:37587909
Abstract

The present study tends to evaluate the possible potential of bio-active Morroniside (MOR), against alloxan (ALX)-induced genotoxicity and hyperglycaemia. prediction revealed the interaction of MOR with Poly (ADP-ribose) polymerase (PARP) protein which corroborated well with experimental L6 cell line and 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.

摘要

本研究旨在评估生物活性莫诺苷(MOR)对抗氧嗪酸钾(ALX)诱导的遗传毒性和高血糖的潜在可能性。预测显示,MOR 与聚 ADP-核糖聚合酶(PARP)蛋白相互作用,这与 L6 细胞系和小鼠模型的实验结果相符。数据显示,MOR 能有效选择性激活 PARP 蛋白,并调节其他应激蛋白 NF-κB 和 TNF-α,从而发挥针对 ALX 诱导的遗传毒性和高血糖的保护作用。此外,通过圆二色性(CD)光谱、紫外-可见(UV-Vis)研究和等温热力学(ITC)数据分析,MOR 与 CT-DNA(小牛胸腺 DNA)的强相互作用表明,涉及抑制染色体畸变和与 DNA 损伤相关的微核形成的生物因子协同作用。最后,MOR 不会抑制微生物生长,这通常是由于高血糖引起的微生物失调所致。因此,从整体研究结果来看,我们可以得出结论,MOR 可能是治疗诱导性高血糖和遗传毒性的潜在药物候选物。通讯作者为 Ramaswamy H. Sarma。

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