Li Yimin, Gong Xiaobing, Peng Yinghua, Kuang Yadang, Huang Jiaxuan, Zheng Mengli, Zhan Leilei, Liang Jiewen, Guo Weiyi
The First Clinical College of Jinan University, Guangzhou, 510632, Guangdong, China.
Department of Gastroenterology, The Tenth Affiliated Hospital, Southern Medical University (Dongguan People's Hospital), Dongguan, 523059, Guangdong, China.
J Mol Histol. 2025 Jul 31;56(4):248. doi: 10.1007/s10735-025-10486-4.
Ulcerative colitis (UC) is a chronic inflammatory disorder characterized by recurrent and intermittent episodes of inflammation. (-)-Myrtenol (MYR) has been shown to exhibit anti-inflammatory, antioxidant, and gastroprotective properties; however, its therapeutic potential in UC remains unexplored. In this study, we established in vitro UC models using lipopolysaccharide (LPS)-induced Caco-2 cells and in vivo models using dextran sulfate sodium (DSS)-induced mice to investigate the effects of MYR on UC. Our findings demonstrated that MYR protected Caco-2 cells from LPS-induced apoptosis and restored mitochondrial function by activating mitophagy. Mechanistically, MYR exerted its protective effects by upregulating ANXA1 expression in LPS-challenged Caco-2 cells, which subsequently activated the PINK1/Parkin pathway. Consistent with these in vitro results, experiments in the DSS-induced mouse model revealed that MYR alleviated UC symptoms and mitigated mitochondrial damage through the regulation of the ANXA1/PINK1/Parkin pathway-mediated mitophagy. In conclusion, MYR reduced apoptosis in LPS-induced Caco-2 cells and ameliorated UC symptoms in DSS-induced mice by enhancing mitophagy and alleviating mitochondrial dysfunction via the ANXA1/PINK1/Parkin pathway.
溃疡性结肠炎（UC）是一种慢性炎症性疾病，其特征为炎症反复发作和间歇性发作。（-）-桃金娘烯醇（MYR）已被证明具有抗炎、抗氧化和胃保护特性；然而，其在UC中的治疗潜力仍未得到探索。在本研究中，我们使用脂多糖（LPS）诱导的Caco-2细胞建立了体外UC模型，并使用葡聚糖硫酸钠（DSS）诱导的小鼠建立了体内模型，以研究MYR对UC的影响。我们的研究结果表明，MYR通过激活线粒体自噬保护Caco-2细胞免受LPS诱导的凋亡并恢复线粒体功能。从机制上讲，MYR通过上调LPS刺激的Caco-2细胞中膜联蛋白A1（ANXA1）的表达发挥其保护作用，随后激活PINK1/Parkin通路。与这些体外结果一致，在DSS诱导的小鼠模型中的实验表明，MYR通过调节ANXA1/PINK1/Parkin通路介导的线粒体自噬减轻UC症状并减轻线粒体损伤。总之，MYR通过增强线粒体自噬并通过ANXA1/PINK1/Parkin通路减轻线粒体功能障碍，减少了LPS诱导的Caco-2细胞中的凋亡并改善了DSS诱导的小鼠的UC症状。
