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

<jats:title>Abstract</jats:title><jats:p>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, <jats:italic>Sanguisorba officinalis L</jats:italic>. (SO) suppressed DSS-induced colitis. To identify the mechanism by which SO ameliorates colitis, epithelial cell and innate myeloid cells-specific <jats:italic>Atg7</jats:italic>-deficient mice (<jats:italic>Villin-cre; Atg7</jats:italic><jats:sup><jats:italic>f/f</jats:italic></jats:sup> and <jats:italic>LysM-cre; Atg7</jats:italic><jats:sup><jats:italic>f/f</jats:italic></jats:sup> mice, respectively) were analyzed. SO-mediated inhibition of colitis was observed in <jats:italic>Villin-cre</jats:italic>; <jats:italic>Atg7</jats:italic><jats:sup><jats:italic>f/f</jats:italic></jats:sup> mice. However, SO and a mixture of its components including catechin acid, ellagic acid, gallic acid, and ziyuglycoside II (Mix<jats:sub>4</jats:sub>) did not suppressed colitis in <jats:italic>LysM-cre</jats:italic>; <jats:italic>Atg7</jats:italic><jats:sup><jats:italic>f/f</jats:italic></jats:sup> mice. In large intestinal macrophages (Mφ) of <jats:italic>Atg7</jats:italic><jats:sup><jats:italic>f/f</jats:italic></jats:sup> mice, SO and Mix<jats:sub>4</jats:sub> upregulated the expression of marker genes of anti-inflammatory Mφ including <jats:italic>Arg1</jats:italic>, <jats:italic>Cd206</jats:italic>, and <jats:italic>Relma</jats:italic>. However, these alterations were not induced in <jats:italic>LysM-cre</jats:italic>; <jats:italic>Atg7</jats:italic><jats:sup><jats:italic>f/f</jats:italic></jats:sup> mice. These findings indicate that SO and its active components ameliorate DSS-induced colitis by providing intestinal Mφ with anti-inflammatory profiles via promotion of Atg7-dependent autophagy.</jats:p>