Hsu Ming-Chun, Wang Han-Tsung, Chen Ching-Yi
Department of Animal Science and Technology, National Taiwan University, Taipei 10672, Taiwan.
Int J Mol Sci. 2025 Apr 8;26(8):3495. doi: 10.3390/ijms26083495.
Oxidative stress impairs intestinal function and causes poor growth performance in piglets. Carvacrol is a natural essential oil, and its anti-oxidative and anti-inflammatory activities in the intestines of piglets have been reported in many studies. However, the mechanisms underlying these protective effects against oxidative stress remain unclear. This study aimed to investigate the possible pathway of carvacrol in the porcine intestine under oxidative stress using an in vitro model. Porcine intestinal epithelial cells (IPEC-J2) were treated with carvacrol and hydrogen peroxide (HO), an oxidative stress inducer, to investigate the protective mechanisms of carvacrol under oxidative stress. We found that carvacrol ameliorated a HO-induced loss of cell viability, apoptosis, and reduced intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) levels. Carvacrol reduced mitochondrial ROS generation and increased citrate synthase activity during oxidative stress. Furthermore, carvacrol attenuated an increase in the autophagy marker LC3II-to-I ratio and reduced the accumulation of lysosomes and autolysosomes induced by HO. The increased protein expression of the mitophagy marker PINK1, induced by HO, was also reduced by carvacrol treatment. Metformin-activated autophagy diminished the protective effects of carvacrol on cell viability and MDA levels under HO treatment, indicating that autophagy inhibition is necessary for carvacrol-induced protection in IPEC-J2 cells during oxidative stress. In conclusion, this study demonstrated the underlying mechanism that carvacrol exerted its anti-oxidative effects on porcine intestinal epithelial cells by relieving excessive autophagy during weaning stress.
氧化应激会损害仔猪的肠道功能并导致生长性能不佳。香芹酚是一种天然精油，许多研究已报道其在仔猪肠道中的抗氧化和抗炎活性。然而，这些针对氧化应激的保护作用的潜在机制仍不清楚。本研究旨在使用体外模型研究香芹酚在氧化应激下对猪肠道可能的作用途径。用香芹酚和氧化应激诱导剂过氧化氢（HO）处理猪肠上皮细胞（IPEC-J2），以研究香芹酚在氧化应激下的保护机制。我们发现香芹酚改善了HO诱导的细胞活力丧失、凋亡，并降低了细胞内活性氧（ROS）和丙二醛（MDA）水平。在氧化应激期间，香芹酚减少了线粒体ROS的产生并增加了柠檬酸合酶的活性。此外，香芹酚减弱了自噬标志物LC3II与I比率的增加，并减少了HO诱导的溶酶体和自噬溶酶体的积累。HO诱导的线粒体自噬标志物PINK1蛋白表达增加也因香芹酚处理而降低。二甲双胍激活的自噬减弱了香芹酚对HO处理下细胞活力和MDA水平的保护作用，表明在氧化应激期间，自噬抑制对于香芹酚诱导的IPEC-J2细胞保护是必要的。总之，本研究证明了香芹酚通过减轻断奶应激期间的过度自噬对猪肠上皮细胞发挥抗氧化作用的潜在机制。
