College of Science, Yunnan Agricultural University, Kunming 650201, China.
Key Laboratory of Pu-er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming 650201, China.
Molecules. 2024 Apr 26;29(9):1999. doi: 10.3390/molecules29091999.
Gallic acid (GA) is a type of polyphenolic compound that can be found in a range of fruits, vegetables, and tea. Although it has been confirmed it improves non-alcoholic fatty liver disease (NAFLD), it is still unknown whether GA can improve the occurrence of NAFLD by increasing the low-density lipoprotein receptor (LDLR) accumulation and alleviating cholesterol metabolism disorders. Therefore, the present study explored the effect of GA on LDLR and its mechanism of action. The findings indicated that the increase in LDLR accumulation in HepG2 cells induced by GA was associated with the stimulation of the epidermal growth factor receptor-extracellular regulated protein kinase (EGFR-ERK1/2) signaling pathway. When the pathway was inhibited by EGFR mab cetuximab, it was observed that the activation of the EGFR-ERK1/2 signaling pathway induced by GA was also blocked. At the same time, the accumulation of LDLR protein and the uptake of LDL were also suppressed. Additionally, GA can also promote the accumulation of forkhead box O3 (FOXO3) and suppress the accumulation of hepatocyte nuclear factor-1α (HNF1α), leading to the inhibition of proprotein convertase subtilisin/kexin 9 (PCSK9) mRNA expression and protein accumulation. This ultimately results in increased LDLR protein accumulation and enhanced uptake of LDL in cells. In summary, the present study revealed the potential mechanism of GA's role in ameliorating NAFLD, with a view of providing a theoretical basis for the dietary supplementation of GA.
没食子酸（GA）是一种多酚化合物，存在于多种水果、蔬菜和茶中。虽然已经证实它可以改善非酒精性脂肪性肝病（NAFLD），但尚不清楚 GA 是否可以通过增加低密度脂蛋白受体（LDLR）积累和缓解胆固醇代谢紊乱来改善 NAFLD 的发生。因此，本研究探讨了 GA 对 LDLR 的影响及其作用机制。研究结果表明，GA 诱导 HepG2 细胞中 LDLR 积累的增加与表皮生长因子受体-细胞外调节蛋白激酶（EGFR-ERK1/2）信号通路的刺激有关。当该途径被 EGFR mab cetuximab 抑制时，观察到 GA 诱导的 EGFR-ERK1/2 信号通路的激活也被阻断。同时，LDLR 蛋白的积累和 LDL 的摄取也受到抑制。此外，GA 还可以促进叉头框 O3（FOXO3）的积累，抑制肝细胞核因子-1α（HNF1α）的积累，从而抑制前蛋白转化酶枯草杆菌蛋白酶/kexin9（PCSK9）mRNA 表达和蛋白积累。这最终导致 LDLR 蛋白积累增加和细胞内 LDL 的摄取增强。综上所述，本研究揭示了 GA 改善 NAFLD 的潜在作用机制，为 GA 的饮食补充提供了理论依据。
