Natural parkin modulators drive mitophagy and overcome metabolic dysfunction-associated fatty liver disease

IF 5.6 1区农林科学 Q1 AGRICULTURAL ENGINEERING

Industrial Crops and Products Pub Date : 2025-06-27 DOI:10.1016/j.indcrop.2025.121404

Xudong He , Mei Zhang , Zhiwei Yang , Rui Ji , Dihong Gong , Yanjuan Li , Shubin Yang , Jie Yu , Feng Xu , Xingxin Yang

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引用次数: 0

Abstract

Metabolic-associated fatty liver disease (MAFLD) is an increasingly common chronic liver disease currently lacking effective treatments. Mitophagy promotion and subsequent enhancement of mitochondrial quality effectively reduce MAFLD. The PINK1/Parkin pathway is involved in the regulation of mitophagy. Therefore, the aim of this work was to explore the effect of naturally occurring Parkin modulators derived from Sophora flavescens on MAFLD. These regulators, including kushenol I, kurarinone, and kushenol F, effectively targeted the active catalytic center of Parkin, consisting of Ubl, RING1, and IBR, and exerted an exceptional regulation of mitophagy and anti-hepatocellular steatosis effect. A prolonged administration of these Parkin regulators ameliorated systemic metabolic disorders and MAFLD induced by a high-fat diet, as a result of the enhancement of Parkin-mediated mitophagy, which improved mitochondrial quality and promoted mitochondrial biogenesis. The 30-day administration and pharmacokinetic characteristics confirmed the suitability of the modulators for therapeutic use. Thus, these three Parkin modulators exhibited promising anti-MAFLD properties, opening up new possibilities in the development of drugs targeting MAFLD.

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天然帕金调节剂驱动线粒体自噬和克服代谢功能障碍相关的脂肪肝疾病

代谢性脂肪性肝病（MAFLD）是一种日益常见的慢性肝病，目前缺乏有效的治疗。线粒体自噬的促进和随后线粒体质量的提高有效地减少了MAFLD。PINK1/Parkin通路参与线粒体自噬的调控。因此，本研究的目的是探讨从苦参中提取的天然Parkin调节剂对MAFLD的影响。这些调节因子包括苦参酚I、苦参酮和苦参酚F，它们有效地靶向Parkin的活性催化中心Ubl、RING1和IBR，并发挥了特殊的调节线粒体自噬和抗肝细胞脂肪变性的作用。长期服用这些帕金调节因子可改善由高脂肪饮食引起的全身性代谢紊乱和MAFLD，这是由于帕金介导的线粒体自噬增强，从而改善线粒体质量并促进线粒体生物发生。30天的给药和药代动力学特征证实了调节剂用于治疗的适用性。因此，这三种Parkin调节剂显示出很好的抗MAFLD特性，为开发针对MAFLD的药物开辟了新的可能性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Industrial Crops and Products 农林科学-农业工程

CiteScore

9.50

自引率

8.50%

发文量

1518

审稿时长

43 days

期刊介绍： Industrial Crops and Products is an International Journal publishing academic and industrial research on industrial (defined as non-food/non-feed) crops and products. Papers concern both crop-oriented and bio-based materials from crops-oriented research, and should be of interest to an international audience, hypothesis driven, and where comparisons are made statistics performed.