6,7-Dihydroxy-2,4-Dimethoxyphenanthrene from Chinese Yam Peels Alleviates DSS-Induced Intestinal Mucosal Injury in Mice via Modulation of the NF-κB/COX-2 Signaling Pathway

In this study, we evaluated the protective effect and molecular mechanism of a dominant phenanthrene, (6,7-dihydroxy-2,4-dimethoxyphenanthrene, CYP4), from Chinese yam peels on intestinal epithelial integrity. Three doses of Chinese yam phenolic extract (CYPE) and Chinese yam phenanthrene 4 (CYP4) were administered to BALB/c mice for 7 days before dextran sulfate sodium (DSS) treatment, with berberine hydrochloride as a positive control (PC). Results showed that both disease activity indexes (DAIs), histological damage score (HDS) and survival rate in DSS mice, were improved with preintervention of CYPE and CYP4, which exhibited better efficiency than PC. Further studies showed that administration of CYP4 downregulated the oxidative stress-associated factors, MPO and NO, and improved tight junction protein occludin. Besides, the CYP4 treatment substantially downregulated the caspase-3 expression and the apoptosis rate of intestinal epithelial cells. In addition, the CYP4 treatment ameliorated the production of inflammatory cytokines including TNF-α, IFN-γ, IL-10, and IL-23 in the colon. Furthermore, the protein expression of ERK1/2, NF-κB p65, pNF-κB, and COX-2 was suppressed in CYE4 groups as compared with that in model control (MC). These findings suggested that CHP4 could effectively inhibit the activation of NF-κB/COX-2 in an experimental UC model in vivo. It was demonstrated for the first time that CYPE and CYP4 protected intestinal mucosa from damage and prevented DSS-induced colitis in mice. CYP4 was one of the active principles obligatory for the biological effect of Chinese yam in protecting intestinal health. These findings indicated that CYP4 might be a promising and useful approach for treatment of UC in humans.