Bergenin, the main active ingredient of <i>Bergenia purpurascens</i> , attenuates Th17 cell differentiation by downregulating fatty acid synthesis

Bergenin is the main active ingredient of Bergenia purpurascens, a medicinal plant which has long been used to treat a variety of Th17 cell-related diseases in China, such as allergic airway inflammation and colitis. This study aimed to uncover the underlying mechanisms by which bergenin impedes Th17 cell response in view of cellular metabolism. In vitro, bergenin treatment reduced the frequency of Th17 cells generated from naïve CD4⁺ T cells of mice. Mechanistically, bergenin preferentially restrained fatty acid synthesis (FAS) but not other metabolic pathways in differentiating Th17 cells, and exogenous addition of either palmitic acid (PA) or oleic acid (OA) and combination with acetyl-CoA carboxylase 1 (ACC1) activator citric acid dampened the inhibition of bergenin on Th17 cell differentiation. Bergenin inhibited FAS through downregulating the expression of SREBP1 via restriction of histone H3K27 acetylation in the SREBP1 promoter, and SREBP1 overexpression weakened the inhibition of bergenin on Th17 differentiation. Furthermore, bergenin was shown to directly interact with SIRT1 and result in activation of SIRT1. Either combination with SIRT1 inhibitor EX527 or point mutation plasmid of SIRT1 diminished the inhibitory effect of bergenin on FAS and Th17 cell differentiation. Finally, the inhibitory effect of bergenin on Th17 cell response and SIRT1 dependence were verified in mice with dextran sulfate sodium-induced colitis. In short, bergenin repressed Th17 cell response by downregulating FAS via activation of SIRT1, which might find therapeutic use in Th17 cell-related diseases.