Astragalus polysaccharide protects sepsis model rats after cecum ligation and puncture

Abstract

To investigate the protective effect and mechanism of Astragalus polysaccharide (APS) on septic rats, the present project applied APS at concentrations of 400, 600, and 800 mg/kg/d to rats for prophylactic administration for 7 d, and a rat sepsis model was constructed by the cecum ligation and puncture (CLP) method. Forty-eight rats were divided into six groups of eight each. Each experiment was repeated at least three times. Rat serum levels of VD3, 25(OH)D3, 1,25(OH)2D3, IL-6, TNF-α, CRP, sICAM-1, corticosterone (CORT), and short-chain fatty acids (SCFAs) in each group were detected, and renal damage was observed by H&E. We also determined the protein expression of CYP27B1, CYP24A1, vitamin D receptor (VDR), steroidogenic acute regulatory protein (STAR), 3β-hydroxysteroid dehydrogenase (3β-HSD), CYP21A2, CYP17A1, and CYP11B1. An operational taxonomic unit (OTU) was used to determine the gut microbiota diversity of septic rats after prophylactic administration and before modeling. Results revealed that APS markedly increased the contents of 25(OH)D3 and 1,25(OH)2D3 but greatly decreased those of TNF-α, IL-6, CRP, sICAM-1, and CORT. APS alleviated renal tubular dilation and vascular congestion in rat kidneys and substantially reduced renal cell apoptosis. Moreover, the expression of CYP24A1, VDR, CYP11B1, CYP21A2, CYP17A1, STAR, and 3β-HSD in the kidneys of the H-APS group was substantially decreased compared to that of the model group, whereas CYP27B1 was markedly increased. GC-MS detection indicated a substantial increase in SCFAs and acetic acid content in the H-APS group versus model group. Through 16S sequencing, the abundance of genus and gut microbiota species increased in the APS groups compared to that of the control group. Taken together, APS increased the activity of the vitamin D axis, inhibited the production of inflammatory factors in the body, altered the structure of rat intestinal flora, and increased the amount of acetic acid and SCFAs in rats, thereby effectively hindering inflammation and organ damage in septic rats.

Modulation of the vitamin D receptor by traditional Chinese medicines and bioactive compounds: potential therapeutic applications in VDR-dependent diseases

“…Additionally, Astragalus polysaccharide has shown immense potential in the treatment of various diseases, including cancer, diabetes, cardiovascular diseases, and liver diseases ( Li et al, 2022b ). Its efficacy extends not only to alleviating these conditions but also to combating sepsis, as revealed by a recent study ( Li et al, 2022c ). This study suggested that the upregulation of adrenocortical VDR activity and vitamin D levels might be the mechanism by which astragalus polysaccharide improves sepsis outcomes.…”

“…The latter is especially significant as these proteins play a crucial role in modulating the gut microbiota flora, specifically, those species that produce short-chain fatty acids. These fatty acids can directly or indirectly mitigate sepsis processes and renal damage induced by sepsis ( Li et al, 2022c ). This is consistent with a previous study that also show the protective effects of astragalus polysaccharide on sepsis-indued acute kidney injury ( Sun et al, 2021 ).…”