Salvianolic acid A (Sal A), a natural polyphenol compounds extracted from Radix Salvia miltiorrhiza (known as Danshen in China), has been shown possessing lots of potential pharmacological activities. This study aimed to investigate the hepatoprotective effects of Sal A against lipotoxicity-induced liver injury in high-fat diet (HFD)-fed c57bl/6 mice and cultured human hepatoma cell line (HepG2), and further explore the potential mechanisms underlying this process. Our results showed that Sal A treatment significantly attenuated HFD-induced weight gain, liver injury, and lipids accumulation in the liver of mice. Sal A incubation markedly reversed palmitic acids-induced cell death in HepG2 cells. Further mechanistic investigations revealed that Sal A treatment did not alleviate lipotoxicity-altered expressions of phosphorylated-JNK, -p38, -ERK1/2, and -PKA in cultured hepatocytes. However, Sal A robustly reversed both HFD- and palmitic acids-decreased AMP-activated protein kinase (AMPK) phosphorylation and sirtuin 1 (SIRT1) expression. Sal A up-regulated phosphorylated-AMPK and SIRT1 expressions in a dose-dependent manner. Silencing either AMPK or SIRT1 gene expression using siRNA abolished Sal A-protected cell death-induced by lipotoxicity. AMPK silencing significantly blocked Sal A-increased SIRT1 expression, otherwise, SIRT1 silencing did not affect Sal A-upregulated phosphorylated-AMPK, indicating AMPK was involved in Sal A-increased SIRT1. Collectively, our data uncover a novel mechanism for Sal A in protecting hepatocytes against lipotoxicity-induced injury of HFD-fed mice liver and palmitic acids-exposed hepatocytes.

Activation of AMPK/SIRT1 pathway contributes to Salvianolic acid A-conferred protection against lipotoxicity in hepatocytes and NAFLD in mice

2019 Fall National Meeting

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