Si-Wu Water Extracts Protect against Colonic Mucus Barrier Damage by Regulating Muc2 Mucin Expression in Mice Fed a High-Fat Diet

A high-fat diet (HFD) could cause gut barrier damage. The herbs in si-wu (SW) include dang gui (Angelica sinensis (Oliv.) Diels), shu di huang (the processed root of Rehmannia glutinosa Libosch.), chuan xiong (rhizome of Ligusticum chuanxiong Hort.), and bai shao (the root of Paeonia lactiflora f. pilosella (Nakai) Kitag.). Si-wu water extracts (SWE) have been used to treat blood deficiency. Components of one herb from SW have been reported to have anti-inflammatory and anti-obesity activities. However, there have been no reports about the effects of SWE on gut barrier damage. Therefore, the aim of the study was to explore the effect of SWE on gut barrier damage. In this study, we found that SWE effectively controlled body weight, liver weight, and feed efficiency, as well as decreased the serum TC level in HFD-fed mice. Moreover, SWE and rosiglitazone (Ros, positive control) increased the colonic alkaline phosphatase (ALP) level, down-regulated serum proinflammatory cytokine levels, and reduced intestinal permeability. In addition, SWE increased goblet cell numbers and mucus layer thickness to strengthen the mucus barrier. After supplementation with SWE and rosiglitazone, the protein expression of CHOP and GRP78 displayed a decrease, which improved the endoplasmic reticulum (ER) stress condition. Meanwhile, the increase in Cosmc and C1GALT1 improved the O-glycosylation process for correct protein folding. These results collectively demonstrated that SWE improved the mucus barrier, focusing on Muc2 mucin expression, in a prolonged high-fat diet, and provides evidence for the potential of SWE in the treatment of intestinal disease-associated mucus barrier damage.