Luo Ruixi, Hu Yudie, Wang La, Ke Zunli, Wang Wenjia, Wang Ping, Tian Weiyi
Department of Immunology and Microbiology School of Basic Medical Sciences, Guizhou University of Traditional Chinese Medicine Guiyang China.
Food Sci Nutr. 2024 Apr 16;12(7):5176-5187. doi: 10.1002/fsn3.4165. eCollection 2024 Jul.
The primary catalyst for nonalcoholic fatty liver disease (NAFLD) is widely recognized as the induction of lipotoxicity in hepatocytes by an excess of fatty acids. In China, Pursh (PcP) is commonly employed as a functional food due to its known hepatoprotective properties. The present study aimed to investigate the influence of PcP extract on in vivo and in vitro models of NAFLD. We found that PcP extract can attenuate palmitic acid (PA)-induced lipotoxicity in HepG2 cells. PA was observed to trigger pyroptosis, as indicated by the increased expression of NLRP3 and GSDMD/N, activation of Caspase-1, and subsequent release of IL-1β and IL-18. However, these changes were reversed after PcP was administered. Furthermore, the application of an NLRP3 agonist inhibited the protective effects of PcP on lipotoxicity, indicating that PcP decreased lipotoxicity by inhibiting the NLRP3/Caspase-1/GSDMD pathway. Ultimately, we established a rat model of NAFLD through the administration of a high-fat diet (HFD), followed by the oral delivery of PcP extracts. The results demonstrated that the administration of PcP extract effectively decreased dyslipidemia and hepatic steatosis, which coincided with a decrease in hepatic pyroptosis through modulation of the NLRP3/Caspase-1/GSDMD pathway in liver tissues. Overall, our findings provide insight into the mechanism by which PcP extracts alleviate hepatic steatosis, highlighting the potential significance of modulating the NLRP3/Caspase-1/GSDMD pathway in the context of pyroptosis.
非酒精性脂肪性肝病（NAFLD）的主要催化剂被广泛认为是过量脂肪酸在肝细胞中诱导的脂毒性。在中国，刺蒺藜（PcP）因其已知的肝脏保护特性而常被用作功能性食品。本研究旨在探讨PcP提取物对NAFLD体内和体外模型的影响。我们发现PcP提取物可以减轻棕榈酸（PA）诱导的HepG2细胞脂毒性。观察到PA引发了细胞焦亡，表现为NLRP3和GSDMD/N表达增加、Caspase-1激活以及随后IL-1β和IL-18的释放。然而，给予PcP后这些变化得到了逆转。此外，应用NLRP3激动剂抑制了PcP对脂毒性的保护作用，表明PcP通过抑制NLRP3/Caspase-1/GSDMD途径降低了脂毒性。最终，我们通过给予高脂饮食（HFD）建立了NAFLD大鼠模型，随后口服PcP提取物。结果表明，给予PcP提取物有效降低了血脂异常和肝脂肪变性，这与通过调节肝组织中的NLRP3/Caspase-1/GSDMD途径减少肝脏细胞焦亡相一致。总体而言，我们的研究结果为PcP提取物减轻肝脂肪变性的机制提供了见解，突出了在细胞焦亡背景下调节NLRP3/Caspase-1/GSDMD途径的潜在意义。
