Dihydromyricetin Protects Intestinal Barrier Integrity by Promoting IL-22 Expression in ILC3s through the AMPK/SIRT3/STAT3 Signaling Pathway

Background: Previous studies indicate that dihydromyricetin (DHM) could alleviate intestinal inflammation and improve intestinal barrier integrity, yet the underlying mechanism remains obscure. Methods: C57BL/6 male mice were fed with a control diet, high-fat diet (HFD), or HFD + DHM diet for 12 weeks. The intestinal permeability and expression of intestinal tight junction (TJ) protein were detected to evaluate the effects of DHM on intestinal barrier integrity. The interleukin 22 (IL-22) production of group 3 innate lymphoid cells (ILC3s) in small intestine lamina propria was tested to clarify the effects of DHM on ILC3s. In addition, an MNK3 cell line, which expresses the same transcription factors and cytokines as ILC3, was used to investigate the molecular mechanism under DHM-induced IL-22 expression. Results: DHM effectively protected HFD-fed mice against intestinal barrier destruction by promoting ILC3 activation and IL-22 secretion, and IL-22 expression increased the expression levels of TJ molecules to protect intestinal barrier integrity. Moreover, DHM increased activation of the AMPK/SIRT3/STAT3 pathway, which in turn promoted IL-22 expression in MNK3 cells. Conclusions: DHM improved IL-22 production in ILC3 cells to alleviate HFD-induced intestinal barrier destruction via the AMPK/SIRT3/STAT3 pathway.