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

Abstract

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 pro-inflammatory 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.

Capsazepine-Induced Altered Colonic Mucosal Health Limits Isomalto-oligosaccharide Action in High-Fat Diet-Fed C57BL/6J Mice

“…Colon innervating TRPA1 and TRPV1 +ve peptidergic sensory neurons regulate intestinal pain during inflammatory conditions like IBD , and are crucial for colonic mucosal health. ,, Our group’s previous research demonstrated the functional role of TRPA1 and TRPV1 channels in the regulation of intestinal mucus homeostasis. ,, CPZ administration inhibits TRPA1- and TRPV1-mediated nociceptive response and has been proposed as a possible candidate for therapeutics for IBD . However, it also reduces gastrointestinal mucus production and alters gut barrier integrity, which contrasts to its protective effects. , HFD feeding has detrimental effects on glucose homeostasis, mucus content in the colon, and gut barrier integrity. ,, Hence, considering the clinical scenario, we studied how HFD consumption affects the colonic mucosal health of mucosal compromised patients (CPZ administered). Furthermore, the efficacy of prebiotics in these conditions was tested.…”

“…18,21 HFD feeding has detrimental effects on glucose homeostasis, mucus content in the colon, and gut barrier integrity. 7,23,24 Hence, considering the clinical scenario, we studied how HFD consumption affects the colonic mucosal health of mucosal compromised patients (CPZ administered). Furthermore, the efficacy of prebiotics in these conditions was tested.…”

Characteristics of mucin hypersecretion in different inflammatory patterns based on endotypes of chronic rhinosinusitis

“…(8) TNF‐α can induce MUC1 gene transcription by activating the MEK1/2/ERK1/Sp1 pathway 52,53 . (9) TNF‐α can induce MUC2 gene transcription by activating the PKC/TK pathway 40,41 …”

“…proposed the following mechanism by which TNF‐α might induce MUC5AC gene expression: TNF‐α activates mitogen, mitogen‐ and stress‐activated protein kinase 1(MSK1), cAMP response element‐binding protein, and cAMP response element through ERK1/2 and p38MAP kinases, thereby causing a signaling cascade and inducing Muc5ac gene expression 39 . In human lung mucoepidermoid cancer cell lines, TNF‐α mediates MUC‐2 gene expression via the protein kinase C and tyrosine kinase signal transduction pathways in a concentration‐dependent manner 40,41 . However, with the increase in goblet cells, mucus gels are formed in the inflammatory region, and make it difficult for TNF‐α to bind with its receptors.…”

“… 39 In human lung mucoepidermoid cancer cell lines, TNF‐α mediates MUC‐2 gene expression via the protein kinase C and tyrosine kinase signal transduction pathways in a concentration‐dependent manner. 40 , 41 However, with the increase in goblet cells, mucus gels are formed in the inflammatory region, and make it difficult for TNF‐α to bind with its receptors. This decrease in binding reduces the pro‐inflammatory effects of TNF‐α.…”