Salvia-Nelumbinis naturalis (SNN) formula is an effective agent in treating nonalcoholic steatohepatitis (NASH); however, the precise mechanisms are still undefined. Activation of Kupffer cells by gut-derived lipopolysaccharide (LPS) plays a central role in the pathogenesis of NASH. In the present study, we aimed to explore the epigenetic regulation of microRNAs under the beneficial effects of SNN-containing serum in LPS stressed macrophages. Kupffer cells were isolated from C57BL/6 mice and treated with LPS or LPS and SNN-containing serum; the mRNA expression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) was assessed. By using microarray chips, we investigated differentially expressed microRNA profiles to decipher the underlining mechanisms of SNN-containing serum. It was revealed that SNN-containing serum decreased TNF-α and IL-6 expression, and microRNA-152 was identified as the potential epigenetic regulator. We further verified the pharmacological effects in Raw264.7 cells; while transfection with miRNA-152 mimics could reduce TNF-α and IL-6, transfection with miRNA-152 inhibitor blocked the anti-inflammatory effect of SNN-containing serum. These results suggested that SNN-containing serum could improve inflammation in LPS stressed Kupffer cells and macrophages via upregulating microRNA-152.
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