Astragalus polysaccharide protects experimental colitis through an aryl hydrocarbon receptor‐dependent autophagy mechanism

Abstract

Background and PurposeDisruption of intestinal barriers plays a vital role in the pathogenesis of colitis. The aryl hydrocarbon receptor (AhR) is a recognition sensor that mediates intestinal immune homeostasis and minimizes intestinal inflammation. Autophagy depends on AhR activation and might constitute a therapeutic target for colitis. Astragalus polysaccharide (APS) exerts pharmacological action in colitis; however, the mechanism has not been elucidated. We aimed to determine whether APS protects colitis through AhR‐dependent autophagy.Experimental ApproachThe symptoms of DSS‐induced colitis mice involving intestinal barrier function and inflammatory injury were evaluated after APS administration. Intestinal‐specific Becn1 conditional knockout mice (Becn1 cKO) were constructed and compared to WT mice. Autophagy and the therapeutic function of APS were investigated after the deactivation of AhR. The relationship between APS‐induced AhR and autophagic Becn1 was investigated using a dual luciferase reporter system and ChIP‐qPCR assay. Caco‐2 cells investigated inflammatory response and AhR‐dependent autophagy.Key ResultsAPS improved intestinal barrier function in the context of inflammatory injury in the colitis mice. APS triggered autophagic flow, however, knockout of the Becn1 in the gut increased susceptibility to colitis, leading to diminished epithelial barrier function and severe intestinal inflammation, furthermore impairing the protective effects of APS. Mechanistically, APS‐triggered autophagy depends on AhR expression. Activated AhR bound to the promoter Becn1 to operate transcription of genes involved in anti‐inflammation and intestinal barrier repair, while deactivation of AhR correlated with intestinal inflammation and the therapeutic function of APS.Conclusion and ImplicationsAPS protects colitis mice by targeting autophagy, especially that AhR stimulate the repair of damaged intestinal barrier functions.

Astragalus Polysaccharide Modulates the Gut Microbiota and Metabolites of Patients with Type 2 Diabetes in an In Vitro Fermentation Model

“…In addition, Supplementary Figure S2 shows that APS concentration at 50–400 µg/mL had no significant effect on Caco2 activity. Consistent with our results, Ying et al [ 27 ] and Wang et al [ 28 ] also found that APS was almost non-toxic to epithelial cells. In Figure S3 , the sequencing depth of samples was seen to sufficiently reflect the composition of most microorganisms in the samples.…”

A Traditional Chinese Medicine, Zhenqi Granule, Potentially Alleviates Dextran Sulfate Sodium-Induced Mouse Colitis Symptoms

“…Moreover, each of the individual components of the formula, Astragali Radix and Fructus Ligustri Lucidi, has been shown to have a therapeutic effect in treating colitis, respectively. Astragalus polysaccharide, an extract of Astragali Radix, showed an anti-colitis effect in DSS-induced mice, which may function through systemic immune regulation [ 27 , 28 , 29 , 30 ]. Yu et al reported that Fructus Ligustri Lucidi had therapeutic efficacy in murine models of experimental colitis by suppressing inflammation and rescuing dysbiosis [ 31 ].…”

Structural Characterization and Screening for Anti‐inflammatory Activity of Polysaccharides with Different Molecular Weights from Astragali Radix

“…[6] Yi Ying et al demonstrated that APSs protected experimental colitis through an aryl hydrocarbon receptordependent autophagy mechanism. [7] APSs have a wide molecular weight distribution and complex branch structure. The vast majority of studies have now concentrated on the whole APSs or a specific component of APSs due to the limits of the current separation and structural analysis technology of polysaccharides.…”