Zhang Teng, Zhou Yong, Zhang Yan, Wang De-Guo, Lv Qiu-Yue, Wang Wen, Bai Ya-Ping, Hua Qiang, Guo Li-Qun
Department of Gastroenterology, The First Affiliated Hospital of Wannan Medical College, Yijishan Hospital, Wuhu, China.
Department of Cardiology, Suzhou Hospital of Anhui Medical University, Suzhou, China.
Front Pharmacol. 2024 Feb 1;15:1347274. doi: 10.3389/fphar.2024.1347274. eCollection 2024.
Sesamin (Ses) is a natural lignan abundantly present in sesame and sesame oil. Pyroptosis, a newly identified type of pro-inflammatory programmed necrosis, contributes to the development of non-alcoholic steatohepatitis (NASH) when hepatocyte pyroptosis is excessive. In this study, Ses treatment demonstrated an improvement in hepatic damage in mice with high-fat, high-cholesterol diet-induced NASH and palmitate (PA)-treated mouse primary hepatocytes. Notably, we discovered, for the first time, that Ses could alleviate hepatocyte pyroptosis both and . Furthermore, treatment with phorbol myristate acetate, a protein kinase Cδ (PKCδ) agonist, increased PKCδ phosphorylation and attenuated the protective effects of Ses against pyroptosis in PA-treated mouse primary hepatocytes. Mechanistically, Ses treatment alleviated hepatocyte pyroptosis in NASH, which was associated with the regulation of the PKCδ/nod-like receptor family CARD domain-containing protein 4/caspase-1 axis. This study introduces a novel concept and target, suggesting the potential use of functional factors in food to alleviate liver damage caused by NASH.
芝麻素（Ses）是一种天然木脂素，大量存在于芝麻和芝麻油中。细胞焦亡是一种新发现的促炎性程序性坏死，当肝细胞焦亡过度时，会促进非酒精性脂肪性肝炎（NASH）的发展。在本研究中，芝麻素治疗可改善高脂、高胆固醇饮食诱导的NASH小鼠以及棕榈酸（PA）处理的小鼠原代肝细胞的肝损伤。值得注意的是，我们首次发现芝麻素可以在体内和体外减轻肝细胞焦亡。此外，用蛋白激酶Cδ（PKCδ）激动剂佛波酯处理可增加PKCδ磷酸化，并减弱芝麻素对PA处理的小鼠原代肝细胞焦亡的保护作用。机制上，芝麻素治疗可减轻NASH中的肝细胞焦亡，这与PKCδ/含半胱天冬酶激活和募集结构域的核苷酸结合寡聚化结构域样受体家族蛋白4/半胱天冬酶-1轴的调节有关。本研究引入了一个新的概念和靶点，提示了食物中的功能因子在减轻NASH所致肝损伤方面的潜在用途。
