Ganjiang Huangqin Huanglian Renshen Decoction protects against ulcerative colitis by modulating inflammation, oxidative stress, and gut microbiota

BACKGROUND: Ulcerative colitis (UC) is a disease that is difficult to treat and has been associated with high rates of recurrence. Moreover, the current medications for UC induce serious side effects following prolonged use. Ganjiang Huangqin Huanglian Renshen Decoction (GJHQHLRSD), has been traditionally used to treat UC. However, its protective mechanisms have not been fully studied. PURPOSE: In this study the mechanisms by which GJHQHLRSD treats UC was investigated. METHODS: The GJHQHLRSD and GJHQHLRSD drug-containing serum (GJHQHLRSD-DS) were characterized using LC-MS/MS. The therapeutic effect of GJHQHLRSD on dextran sodium sulfate (DSS)-induced UC was explored by assessing various parameters including intestinal flora 16S rRNA, intestinal barrier function, oxidative stress (OS) response, inflammatory cytokines, colonic histopathological injury, colon length, disease activity index (DAI) and body weight. RESULTS: Treatment with GJHQHLRSD increased body weight, ameliorated colon length shortening and edema, reduced the DAI score, improved the pathological injury, down-regulated the levels of IL-1β, IL-6, IL-8, TNF-α, LPS, LDH, TLR4, and NLRP3, and up-regulated the ZO-1 and Occludin levels in UC mice. It also decreased intestinal oxidative stress in UC mice and improved mitogenic activity by modulating mitochondrial ultrastructure as well as the expression level of PINK1, LC3-II/Ⅰ, Beclin-1, p62, and Parkin proteins. In addition, we found that the effects of GJHQHLRSD on UC mice were inhibited by 3-MA.GJHQHLRSD treatment reduced the imbalance of intestinal flora in UC mice, by regulating the inflammation and oxidative stress. CONCLUSION: These findings suggested that GJHQHLRSD effectively attenuated inflammatory responses, inhibited the TLR4/NF-κB/NLRP3 signalling, oxidative stress, and modulated the gut microbiota, and alleviated the DSS-induced UC symptoms, making it a promising and innovative therapeutic option for the treatment of UC.