Abstract：
Diabetic liver injury (DLI) is one of the complications of diabetes mellitus, which seriously jeopardizes human health. Punicalagin (PU), a polyphenolic compound mainly found in pomegranate peel, has been shown to ameliorate metabolic diseases such as DLI, and the mechanism needs to be further explored. In this study, a HFD/STZ-induced diabetic mouse model is established to investigate the effect and mechanism of PU on DLI. The results show that PU intervention significantly improves liver histology and serum biochemical abnormalities in diabetic mice, significantly inhibits the expression of pyroptosis-related proteins such as NLRP3, Caspase1, IL-1β, and GSDMD in the liver of diabetic mice, and up-regulated the expression of autophagy-related proteins. Meanwhile, PU treatment significantly increases FoxO1 protein expression and inhibits TXNIP protein expression in the liver of diabetic mice. The above results are further verified in the HepG2 cell injury model induced by high glucose. AS1842856 is a FoxO1 specific inhibitor. The intervention of AS1842856 combined with PU reverses the regulatory effects of PU on pyroptosis and autophagy in HepG2 cells. In conclusion, this study demonstrates that PU may inhibit pyroptosis and upregulate autophagy by regulating FoxO1/TXNIP signaling, thereby alleviating DLI.
摘要：
糖尿病肝损伤(DLI)是糖尿病的并发症之一。严重危害人类健康。Punicalagin(PU),一种主要存在于石榴皮中的多酚类化合物，已被证明可以改善代谢疾病，如DLI，机制有待进一步探索。在这项研究中,建立HFD/STZ诱导的糖尿病小鼠模型，研究PU对DLI的影响及其机制。结果表明，PU干预显著改善糖尿病小鼠肝脏组织学和血清生化异常，显著抑制NLRP3、Caspase1、IL-1β、糖尿病小鼠肝脏中的GSDMD，并上调自噬相关蛋白的表达。同时,PU处理显著增加糖尿病小鼠肝脏中FoxO1蛋白表达并抑制TXNIP蛋白表达。以上结果在高糖诱导的HepG2细胞损伤模型中得到进一步验证。AS1842856是FoxO1特异性抑制剂。AS1842856联合PU的干预作用逆转了PU对HepG2细胞焦凋亡和自噬的调控作用。总之,这项研究表明，PU可能通过调节FoxO1/TXNIP信号抑制细胞凋亡和上调自噬，从而减轻DLI。
