Pharmacological Research | VOL. 182
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Paeoniflorin prevents aberrant proliferation and differentiation of intestinal stem cells by controlling C1q release from macrophages in chronic colitis

Publication Date Aug 1, 2022

Abstract

The pathological features of inflammatory bowel disease necessitate therapeutic strategies aimed at restoring intestinal mucosal barrier function in addition to controlling inflammation. Paeoniflorin, a bioactive herbal constituent isolated from the root of Paeonia albiflora Pall, has been reported to protect against acute colitis in mice. However, the direct molecular target of paeoniflorin in preventing colitis remains elusive. Here, we evaluated the therapeutical effects of Paeoniflorin using IL-10-/- chronic colitis model, and explored the precise mechanism of action involved. Our results demonstrated that intragastric administration of Paeoniflorin significantly ameliorated inflammatory response and restored the aberrant intestinal proliferation and differentiation in IL-10-/-colitis mice. By utilizing a chemical biology approach, we identified C1qa, a crucial component of C1q, is the direct target of Paeoniflorin. Binding of Paeoniflorin to C1qa prevented the cleavage of C1q on macrophages, resulting in the aggregation of surface membrane-anchored C1q and the diminished C1q secretion. The excessive surface membrane-anchored C1q significantly enhanced the phagocytic capability of macrophages and promoted the elimination of infiltrated bacteria and inflammatory cells in mouse colon. The reduced C1q secretion conferred by Paeoniflorin dampened Wnt/β-catenin signaling activation, thereby rectifying the aberrant proliferation and differentiation of intestinal stem cells (ISCs). In summary, our study demonstrates that Paeoni...

Concepts

Differentiation Of Intestinal Stem Cells Aberrant Proliferation Chronic Colitis Model Proliferation Of Intestinal Stem Cells Acute Colitis In Mice Cells In Mouse Colon Features Of Inflammatory Bowel Disease Aberrant Proliferation Of Cells Differentiation Of Intestinal Cells Proliferation Of Intestinal Cells

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