Purple sweet potato color protects against hepatocyte apoptosis through Sirt1 activation in high-fat-diet-treated mice

Abstract

Background: 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. Objective: Here we investigated the effects of PSPC on HFD-induced hepatic apoptosis and the mechanisms underlying these effects. Design: 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 Sirt1 siRNA were used to demonstrate the Sirt1 dependence of PSPC-mediated effects on apoptotic and survival signaling pathways in vivo and in vitro. Results: 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, Sirt1 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. Conclusion: 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.

Sweet Potato Leaf Feeding Decreases Cholesterol, Oxidative Stress and Thrombosis Formation in Syrian Hamsters with a High-Cholesterol Diet

“…SPL has been noted for its beneficial effects in the treatment of hyperglycemia or as a food additive for the prevention of type 2 diabetes via the activation of GLUT4 and the regulation of the PI3K/AKT pathway [ 36 ]. In addition, an extract of sweet potato exerts hepatic protection and treatment potential for non-alcoholic fatty liver disease [ 6 , 37 ]. In our study, hepatic SREBP-1 expression was elevated by SPLP feeding.…”

Metabolic Impact of Flavonoids Consumption in Obesity: From Central to Peripheral

“…All these data confirm the impact of anthocyanins and even in a more significative way of the anthocyanin-rich foods on metabolism. These effects can be added to their anti-inflammatory, antiapoptotic, pro-autophagic and antioxidant properties in steatotic livers [ 59 , 62 , 102 , 103 , 104 ].…”

Immune-Enhancing Effects of a Novel Glucan from Purple Sweet Potato Ipomoea batatas (L.) Lam on RAW264.7 Macrophage Cells via TLR2- and TLR4-Mediated Pathways

“…Sweet potato (Ipomoea batatas) is a kind of both edible and medicinal agricultural food, which provides a dietary source of vitamins, minerals, carbohydrates, proteins, anthocyanins, essential fatty acids, trace elements, and other nutrients, and these active substances play roles in many pharmacological activities such as antitumor, immune regulation, hepatoprotective effect, hypoglycemic effect, hypolipidemic effect, antiaging, intestinal regulation, , antiobesity, antifatigue, and so on . Some water-soluble bioactive polysaccharides and alkali-soluble bioactive polysaccharides have been purified from purple sweet potato. − In our recent report, a new 18.3 kDa homogeneous polysaccharide component named PSPP-1 was isolated from purple sweet potato, and its structures were elucidated comprehensively for the first time, which was very useful for its further structure–activity relationship study.…”