Su Weitong, Zhang Cheng, Chen Feng, Sui Junwen, Lu Jiaqi, Wang Qingqing, Shan Qun, Zheng Guihong, Lu Jun, Sun Chunhui, Fan Shaohua, Wu Dongmei, Zhang Zifeng, Zheng Yuanlin
Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, College of Health Science, Jiangsu Normal University, Xuzhou, Jiangsu Province, P. R. China.
Food Nutr Res. 2020 Feb 4;64. doi: 10.29219/fnr.v64.1509. eCollection 2020.
Recent evidence indicates that the inhibition of hepatocyte apoptosis is possible to develop a potential therapeutic strategy for nonalcoholic fatty liver disease (NAFLD). Our previous work suggested that purple sweet potato color (PSPC), a class of naturally occurring anthocyanins, effectively improved many features of high-fat diet (HFD)-induced NAFLD. However, whether PSPC ameliorates HFD-induced hepatocyte apoptosis has never been investigated.
Here we investigated the effects of PSPC on HFD-induced hepatic apoptosis and the mechanisms underlying these effects.
Mice were divided into four groups: Control group, HFD group, HFD + PSPC group and PSPC group. PSPC was administered by daily oral gavage at doses of 700 mg/kg/day for 20 weeks. EX-527 (a SirT1-selective inhibitor) and siRNA were used to demonstrate the Sirt1 dependence of PSPC-mediated effects on apoptotic and survival signaling pathways and .
Our results showed that PSPC reduced body weights, hepatic triglyceride contents, histopathological lesions and serum ALT levels in a mouse model of NAFLD induced by HFD. Furthermore, PSPC attenuated HFD-induced hepatocyte apoptosis ratio from 7.27 ± 0.92% to 1.79 ± 0.27% in mouse livers, which is insignificant compared with that of controls. Moreover, PSPC activated Sirt1 by boosting NAD level in HFD-treated mouse livers. Furthermore, PSPC promoted Sirt1-dependent suppression of P53-mediated apoptotic signaling and activation of Akt survival signaling pathway in HFD-treated mouse livers, which was confirmed by EX527 treatment. Moreover, knockdown abolished these ameliorative effects of PSPC on apoptosis and P53 acetylation and protein expression in PA-treated L02 cells. Ultimately, PSPC reduced Caspase-3 activation and Bax level, and elevated the Bcl-2 level in HFD-treated mouse livers.
PSPC protected against HFD-induced hepatic apoptosis by promoting Sirt1- dependent inhibition of p53-apoptotic pathway and facilitation of Akt survival pathway. This study indicates that PSPC is a candidate for nutritional intervention of NAFLD.
最近的证据表明，抑制肝细胞凋亡可能为非酒精性脂肪性肝病（NAFLD）开发一种潜在的治疗策略。我们之前的研究表明，紫甘薯色素（PSPC），一类天然存在的花青素，能有效改善高脂饮食（HFD）诱导的NAFLD的许多特征。然而，PSPC是否能改善HFD诱导的肝细胞凋亡从未被研究过。
在此，我们研究了PSPC对HFD诱导的肝脏凋亡的影响及其潜在机制。
将小鼠分为四组：对照组、HFD组、HFD + PSPC组和PSPC组。PSPC以700 mg/kg/天的剂量每日经口灌胃给药20周。使用EX-527（一种SirT1选择性抑制剂）和小干扰RNA（siRNA）来证明PSPC介导的对凋亡和生存信号通路的影响对Sirt1的依赖性。
我们的结果表明，在HFD诱导的NAFLD小鼠模型中，PSPC降低了体重、肝脏甘油三酯含量、组织病理学损伤和血清ALT水平。此外，PSPC使HFD诱导的小鼠肝脏中肝细胞凋亡率从7.27±0.92%降至1.79±0.27%，与对照组相比无显著差异。此外，PSPC通过提高HFD处理的小鼠肝脏中的NAD水平来激活Sirt1。此外，PSPC促进了HFD处理的小鼠肝脏中Sirt1依赖性抑制P53介导的凋亡信号和Akt生存信号通路，这通过EX527处理得到证实。此外，小干扰RNA敲低消除了PSPC对棕榈酸（PA）处理的L02细胞凋亡、P53乙酰化和蛋白表达的这些改善作用。最终，PSPC降低了HFD处理的小鼠肝脏中Caspase-3的激活和Bax水平，并提高了Bcl-2水平。
PSPC通过促进Sirt1依赖性抑制p53凋亡途径和促进Akt生存途径，保护肝脏免受HFD诱导的凋亡。本研究表明，PSPC是NAFLD营养干预的一个候选物。
