Ginsenoside Rg3 treats acute radiation proctitis through the TLR4/MyD88/NF-kB pathway and regulation of intestinal flora

Objectives: This study aimed to investigate the protective effect of ginsenosideRg3 (GRg3) against acute radiation proctitis (ARP) in rats.Methods: Wistar rats were randomly divided into control, model,dexamethasone-positive, GRg3 low-dose, GRg3 medium-dose, and GRg3high-dose groups. The ARP rat model was established by a single 22-Gyirradiation of 6 MV) X-rays. The distribution and function of intestinal florawere detected using 16S rRNA high-throughput sequencing, rectal tissue wasobserved by hematoxylin and eosin (H&E) staining, the expression of interleukin Q71b (IL-1b) and IL-10 inflammatory factors was detected by ELISA, and mRNAand protein expression of toll-like receptor 4 (TLR4), myeloid differentiationprimary response 88 (MyD88), and NF-kB) were detected by RT-qPCR andWestern blotting, respectively.Results: GRg3 improved the symptoms of ARP in rats in a dose-dependentmanner. The species distribution of intestinal flora in GRg3 rats was significantlydifferent from that in ARP rats. These differences were more significant in thehigh-dose group, where the numbers of Ruminococcus, Lactobacillus, andother beneficial bacteria were significantly increased, whereas those ofEscherichia, Alloprevotella, and other harmful bacteria were decreased. Inaddition, GRg3 was closely related to amino acid metabolism. After GRg3treatment, the mRNA and protein expression of TLR4, MyD88, and NF-kB inrectal tissue was significantly down-regulated, and the content of downstreaminflammatory factor IL-1b decreased, whereas that of IL-10 increased.Conclusion: Our study indicated GRg3 as a new compound for the treatmentof ARP by inhibiting the TLR4/MyD88/NF-kB pathway, down-regulating theexpression of proinflammatory factors, thus effectively regulating intestinalflora and reducing inflammatory reactions.