Xuanfei Baidu decoction attenuates intestinal disorders by modulating NF-κB pathway, regulating T cell immunity and improving intestinal flora

Background: A number of studies have shown that gastrointestinal manifestations co-exist with respiratory symptoms in coronavirus disease 2019 (COVID-19) patients. Xuanfei Baidu decoction (XFBD) was recommended by the National Health Commission to treat mild and moderate COVID-19 patients and proved to effectively alleviate intestinal symptoms. However, the exact mechanisms remain elusive. Purpose: This study aimed at exploring potential mechanisms of XFBD by utilizing a mouse model of dextran sulfate sodium (DSS)-induced acute experimental colitis, mimicking the disease conditions of intestinal micro-ecological disorders. Methods: The network pharmacology approach was employed to identify the potential targets and pathways of XFBD on the intestinal disorders. Mice with DSS-induced intestinal disorders were utilized to evaluate the protective effect of XFBD in vivo, including body weight, disease activity index (DAI) score, colon length, spleen weight, and serum tumor necrosis factor-alpha (TNF-alpha) level. Colon tissues were used to perform hematoxylin-eosin (H&E) staining, western blot analysis, and transcriptome sequencing. Macrophages, neutrophils and the pro-portions of T helper cell (Th) 1 and Th2 cells were measured by flow cytometry. Intestinal contents were collected for 16S rRNA gene sequencing. Results: Network pharmacology analysis indicated that XFBD inhibited the progression of COVID-19-related intestinal diseases by repressing inflammation. In mice with DSS-induced intestinal inflammation, XFBD treat-ment significantly reduced weight loss, the spleen index, the disease activity index, TNF-alpha levels, and colonic tissue damage, and prevented colon shortening. Transcriptomics and flow cytometry results suggested that XFBD remodeled intestinal immunity by downregulating the Th1/Th2 ratio. Western blot analysis showed that XFBD exerted its anti-inflammatory effects by blocking the nuclear factor-kappa B (NF-kappa B) signaling pathway. Indicator analysis of microbiota showed that 75 operational taxonomic units (OTUs) were affected after XFBD adminis-tration. Among them, Akkermansia, Muribaculaceae, Lachnospiraceae, and Enterorhabdus were simultaneously negatively correlated with intestinal disorders' parameters, and Bacteroides, Escherichia-Shigella, Eubacterium nodatum,Turicibacter, and Clostridium sensu stricto 1, showed positive correlations with intestinal disorders' parameters. Conclusions: Our data indicate that XFBD treatment attenuated intestinal disorders associated with inhibiting inflammation, remodeling of intestinal immunity, and improving intestinal flora. These findings provide a scientific basis for the clinical use of XFBD and offer a potential therapeutic approach for the treatment of COVID-19 patients with intestinal symptoms.