Sijunzi Decoction attenuates 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats and ameliorates TNBS-induced claudin-2 damage via NF-κB pathway in Caco2 cells

BMC Complement Altern Med. 2017 Jan 10;17(1):35. doi: 10.1186/s12906-016-1549-3.

Abstract

Background: SijunziDecoction (SJZD) is a traditional Chinese medicine prescription used to treat the diseases of gastrointestinal tract since ancient times. The objective of this study was to investigate the protective effects of SJZD on TNBS-induced colitis in rats and TNBS-damaged Caco2 cells.

Methods: The rat colitis model was induced by 2, 4, 6-trinitrobenzene sulfonic acid (TNBS). SJZD (2.8 5.6, 11.2 g/kg) or salazosulfapyridine (SASP) (0.4 g/kg) was administrated orally in rats for 7 days. DAI, pathological scores and the expression of claudin-2 were evaluated. Then we explored the effect and mechanism of SijunziDecoction Serum (SJZDS) onTNBS-damaged Caco2 cells to figure out intestinal barrier protective effect and mechanism of SJZD.

Results: SJZD significantly ameliorated the severity of TNBS-induced colitis and downregulated the level of claudin-2 in colonic tissues. SJZDS promoted proliferation and inhibited apoptosis ofTNBS-damaged Caco2 cells. In Caco2 cell monolayers, we provided mechanistic evidence that SJZDS-induced increased TEER and decreased permeability after TNBS damage, which were mediated through claudin-2 and NF-κB pathway, including the upregulation of claudin-2, decreased activity of NF-κB p65, reduced level of NF-κB p65 and MLCK.

Conclusions: Our results indicated that SJZD possesses protective effect of intestinal barrier towards TNBS-induced colitis in rats and TNBS-damaged Caco2 cells in vitro. SJZDis a potential protective agent of intestinal barrier that deserves further investigation.

Keywords: Claudin-2; Inflammatory bowel disease; NF-κB pathway; SijunziDecoction; Tight junction.

MeSH terms

  • Animals
  • Caco-2 Cells
  • Claudin-2 / genetics
  • Claudin-2 / metabolism*
  • Colitis / chemically induced
  • Colitis / drug therapy*
  • Colitis / genetics
  • Colitis / metabolism
  • Drugs, Chinese Herbal / administration & dosage*
  • Humans
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / metabolism
  • Male
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Rats
  • Signal Transduction / drug effects
  • Trinitrobenzenesulfonic Acid

Substances

  • Claudin-2
  • Drugs, Chinese Herbal
  • NF-kappa B
  • Trinitrobenzenesulfonic Acid