Huai hua san alleviates dextran sulphate sodium-induced colitis and modulates colonic microbiota

J Ethnopharmacol. 2020 Sep 15:259:112944. doi: 10.1016/j.jep.2020.112944. Epub 2020 May 5.

Abstract

Ethnopharmacological relevance: Huai hua san (HHS) is a traditional Chinese herbal formula which is firstly documented in the ancient Chinese classic medical work "Pu Ji Ben Shi Fang" in 1132 AD. It has been widely used in the treatment of lower gastrointestinal disorders such as acute colitis and hematochezia for more than 800 years. However, scientific evidence of the efficacy and the exact mechanism of HHS against colitis has not yet been reported.

Aim of the study: The aim of this study is to investigate the potential effects of HHS in the alleviation of dextran sulphate sodium (DSS)-induced colitis and the alteration of colonic microbiota composition and structure.

Materials and methods: HHS solution was orally administrated to 5% DSS-challenged rats once a day for 8 days. Colitis clinical symptoms of colitis were collected, together with colonic mucosal damage assessed at histomorphometric and ultrastructural levels. The protein levels of inflammatory mediators TNF-α and CRP were detected by ELISA. The colonic vascular permeability was evaluated by Evans blue extravasation. Meanwhile, The effects of the HHS therapy on the colonic microbiota were evaluated by analyzing the V3 and V4 regions of the 16S rRNA gene by Illumina sequencing and multivariate statistical methods.

Results: Daily oral administration of HHS markedly alleviated DSS-induced colitis, as evidenced by decreased colitis disease activity index (DAI) score, reduced colonic inflammation and normalization of colonic vascular hyperpermeability. Moreover, the 16S rRNA gene sequencing analysis demonstrated that HHS treatment during colitis prevented the colitis-associated alteration of colonic microbial community at operational taxonomic unit level, together with the DSS-induced colonic microbiota dysbiosis at taxonomic levels. In addition, HHS therapy reduced colitis-associated high increased ratio of Bacteroidetes to Firmicutes to a normal level.

Conclusion: HHS could attenuate ulcerative colitis and ameliorate gut microbial dysbiosis.

Keywords: Colonic microbiota; Gut microbial dysbiosis; Gut-vascular barrier; Huai hua san; Ulcerative colitis.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Bacteria / classification
  • Bacteria / drug effects*
  • Bacteria / growth & development
  • Carrier Proteins / metabolism
  • Colitis / chemically induced
  • Colitis / drug therapy*
  • Colitis / metabolism
  • Colitis / microbiology
  • Colon / drug effects*
  • Colon / metabolism
  • Colon / microbiology
  • Colon / ultrastructure
  • Dextran Sulfate
  • Disease Models, Animal
  • Drugs, Chinese Herbal / pharmacology*
  • Dysbiosis
  • Gastrointestinal Microbiome / drug effects*
  • Inflammation Mediators / metabolism
  • Male
  • Permeability
  • Rats, Sprague-Dawley
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • Carrier Proteins
  • Crp protein, rat
  • Drugs, Chinese Herbal
  • Inflammation Mediators
  • Tumor Necrosis Factor-alpha
  • huai hua san
  • Dextran Sulfate