Li Yanjuan, Wang Pengquan, Yang Huan, He Jinbiao, Yang Yu, Tao Yuxuan, Zhang Min, Zhang Mei, Yu Jie, Yang Xingxin
College of Pharmaceutical Science, Yunnan University of Chinese Medicine, 1076 Yuhua Road, Kunming, 650500, China.
Yunnan Key Laboratory of Southern Medicine Utilization, 1076 Yuhua Road, Kunming, 650500, China.
Heliyon. 2024 Aug 3;10(16):e35645. doi: 10.1016/j.heliyon.2024.e35645. eCollection 2024 Aug 30.
Currently, no specific treatment exists to alleviate metabolic dysfunction-associated fatty liver (MAFLD). Previously, (PC) effectively relieved MAFLD, but its bioactive components are still unknown. The bioactive substances in PC that regulate mitochondria function to alleviate MAFLD were thus determined. The L02 hepatocyte model induced by fat emulsion and the MAFLD rat model induced by a high-fat diet (HFD) were developed to explore the efficacy of PC against MAFLD. The activity of PC-derived components in the liver mitochondria of HFD-fed rats was evaluated using the L02 hepatocyte model. Additionally, the PC-derived components from the liver mitochondria were identified by ultra-high performance liquid chromatography/mass spectrometry. Finally, the -steatosis ability of PC-derived monomers and monomers groups was evaluated using the adipocyte model. PC maintained the mitochondrial ultrastructure, alleviated mitochondrial oxidative stress, and regulated the energy metabolism and the fatty acid β oxidation to relieve lipid emulsion-induced cellular steatosis and HFD-induced MAFLD. PC-derived components entering the liver mitochondria inhibited oxidative stress injury and improved the energy metabolism to fight cellular steatosis. Additionally, 15 chemicals were identified in the PC-treated rat liver mitochondria. These identified chemical molecules and molecule groups in the mitochondria prevented cellular steatosis by regulating mitochondrial oxidative stress and energy metabolism. PC restores mitochondrial structure and function, alleviating MAFLD, which is related to oxidative stress, energy metabolism, and fatty acid β oxidation. The identified 15 components may be the main effective PC components regulating mitochondria function to alleviate MAFLD. Thus, PC may be a promising mitochondrial regulator to prevent MAFLD.
目前，尚无特定疗法可缓解代谢功能障碍相关脂肪性肝病（MAFLD）。此前，（某种物质）（PC）可有效缓解MAFLD，但其生物活性成分仍不明确。因此，确定了PC中调节线粒体功能以缓解MAFLD的生物活性物质。构建了脂肪乳诱导的L02肝细胞模型和高脂饮食（HFD）诱导的MAFLD大鼠模型，以探究PC对MAFLD的疗效。使用L02肝细胞模型评估HFD喂养大鼠肝脏线粒体中PC衍生成分的活性。此外，通过超高效液相色谱/质谱法鉴定肝脏线粒体中PC衍生的成分。最后，使用脂肪细胞模型评估PC衍生单体和单体组的抗脂肪变性能力。PC维持线粒体超微结构，减轻线粒体氧化应激，并调节能量代谢和脂肪酸β氧化，以缓解脂质乳剂诱导的细胞脂肪变性和HFD诱导的MAFLD。进入肝脏线粒体的PC衍生成分抑制氧化应激损伤并改善能量代谢，以对抗细胞脂肪变性。此外，在PC处理的大鼠肝脏线粒体中鉴定出15种化学物质。线粒体中这些鉴定出的化学分子和分子组通过调节线粒体氧化应激和能量代谢来防止细胞脂肪变性。PC恢复线粒体结构和功能，减轻与氧化应激、能量代谢和脂肪酸β氧化相关的MAFLD。鉴定出的15种成分可能是PC调节线粒体功能以缓解MAFLD的主要有效成分。因此，PC可能是预防MAFLD的一种有前景的线粒体调节剂。
