Bu-Zhong-Yi-Qi Granule Enhances Colonic Tight Junction Integrity via TLR4/NF-κB/MLCK Signaling Pathway in Ulcerative Colitis Rats

Abstract

Background. Bu-zhong-yi-qi granule (BZYQ), a sort of Chinese herbal medicine, has exhibited therapeutic effects on ulcerative colitis (UC). However, the mechanism of BZYQ has not been fully clarified. This study was aimed at investigating the effects of BZYQ on UC rats model and at exploring its potential mechanism. Methods. The UC rats were established by enema of trinitrobenzene sulfonic acid (TNBS). The therapeutic effects of BZYQ treatment were evaluated by disease activity index (DAI), colon macroscopic damage index (CMDI) scores, and histological observation. The mRNA levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-10 (IL-10) were measured by quantitative real time-polymerase chain reaction (qPCR). The expression of tight junction (TJ) proteins, occludin and claudin-1, in the colon was determined by Western blot and immunofluorescence. The expression of toll-like receptors 4 (TLR4), nuclear factor-kappa B (NF-κB), p-NF-κB, myosin light chain kinase (MLCK), MLC, and p-MLC levels in colon was determined by Western blot or qPCR. Results. The results showed that BZYQ could attenuate DAI, CMDI, and histological inflammation. TJ proteins expression was decreased in UC rats, but treatment with BZYQ restored the expression of occludin and claudin-1. In addition, BZYQ administration ameliorated UC-associated increase in the production of TNF-α, IL-1β, and the expression of TLR4, NF-κB, p-NF-κB, MLCK, MLC, and p-MLC, while BZYQ administration increased the production of IL-10. Conclusions. The therapeutic effect of BZYQ on UC is at least partially through regulation of the secretion of some inflammatory cytokines and improvement of TJ integrity via TLR4/NF-κB/MLCK pathway.

Lead exposure exacerbates liver injury in high-fat diet-fed mice by disrupting the gut microbiota and related metabolites

“…32 NFκB promotes the activation of MLCK, redistributes tight junctions and damages the intestinal barrier. 33 Cheng et al found that an HFD can lead to the activation of NFκB–MLCK and damage intestinal integrity, 34 which is similar to our research results. Notably, the further activation after Pb exposure is most likely mediated by elevated levels of LPS.…”

Inflammatory bowel disease: an overview of Chinese herbal medicine formula-based treatment

“…et Zucc., Atractylodes lancea (Thunb) DC and Glycyrrhiza glabra L. DSS-induced UC rats Inhibit TLR4/NF-κB signaling pathway, inhibit PI3K/AKT/NF-κB signaling pathway and oxidative stress [ 61 ] Bu-Zhong-Yi-Qi Granule Astragalus, Codonopsis pilosula (Franch.) Nannf., Liquorice, Atractylodes macrocephala , Tangerine peel, Cohosh, Bupleurum, Angelica, Zingiber officinale Roscoe, and Jujube TNBS-induced UC rats Restore the expression of TJ protein and regulate the secretion of some inflammatory cytokines through the TLR4/NF-κB/MLCK pathway [ 64 ] Shen-Ling-Bai-Zhu-San Panax ginseng C. A. Mey. , Poria cocos (Schw.)…”

“…A variety of signaling pathways are involved in the activation of MLCK, mainly through the mitogen-activated protein kinase (MAPK) pathway of extracellular regulated protein kinase (ERK) 1/2, P38, c-Jun N-terminal kinase (JNK) pathway, as well as inflammation-related pathways involved in cell proliferation and apoptosis [ 63 ]. In TNBS-induced UC rats, Bu-Zhong-Yi-Qi Granule can regulate the secretion of some inflammatory cytokines and improve TJ integrity through TLR4/NF-κB/MLCK pathway [ 64 ]. Sijunzi Decoction could reduce the levels of NF-κB p65 and MLCK [ 17 ].…”

Senegalia macrostachya seed polysaccharides attenuate inflammation-induced intestinal epithelial barrier dysfunction in a Caco-2 and RAW264.7 macrophage co-culture model by inhibiting the NF-κB/MLCK pathway

“…This result was also supported by previous investigators who reported that inflammation-induced intestinal barrier function loss was related to the upregulation of the NF-kB/MLCK pathway. 89,90 SMSP2 treatment downregulated MLCK and p-MLC, implying that its protective effect was mediated by inhibiting the MLCK signaling pathways. The possible molecular mechanism is summarized in Fig.…”