Sanguisorba officinalis L. derived from herbal medicine prevents intestinal inflammation by inducing autophagy in macrophages

Abstract

Disturbed activation of autophagy is implicated in the pathogenesis of inflammatory bowel disease. Accordingly, several autophagy-related genes have been identified as Crohn's disease susceptibility genes. We screened the autophagy activators from a library including 3,922 natural extracts using a high-throughput assay system. The extracts identified as autophagy activators were administered to mice with 2% dextran sodium sulfate (DSS). Among the autophagy inducers, Sanguisorba officinalis L. (SO) suppressed DSS-induced colitis. To identify the mechanism by which SO ameliorates colitis, epithelial cell and innate myeloid cells-specific Atg7-deficient mice (Villin-cre; Atg7(f/f) and LysM-cre; Atg7(f/f) mice, respectively) were analyzed. SO-mediated inhibition of colitis was observed in Villin-cre; Atg7(f/f) mice. However, SO and a mixture of its components including catechin acid, ellagic acid, gallic acid, and ziyuglycoside II (Mix(4)) did not suppressed colitis in LysM-cre; Atg7(f/f) mice. In large intestinal macrophages (M phi) of Atg7(f/f) mice, SO and Mix(4) upregulated the expression of marker genes of anti-inflammatory M phi including Arg1, Cd206, and Relma. However, these alterations were not induced in LysM-cre; Atg7(f/f) mice. These findings indicate that SO and its active components ameliorate DSS-induced colitis by providing intestinal M phi with anti-inflammatory profiles via promotion of Atg7-dependent autophagy.