Anticolitic Effect of Berberine in Rat Experimental Model: Impact of PGE2/p38 MAPK Pathways

Abstract

Berberine (BER), a natural isoquinoline alkaloid, has been demonstrated to have appreciable anticolitis effects. Nevertheless, the protective mechanism of BER in ulcerative colitis (UC) is barely understood. The present study was aimed at exploring the therapeutic efficacy of BER on UC in experimental colitis rat model. Rats were orally administered with BER for seven days at low and high doses (25 and 50 mg/kg/day) before AcOH intracolonic instillation. BER significantly retrieved colon inflammation and mucosal damage indicated by inhibition of macroscopic score and lessened the levels of inflammatory biomarkers (IL-1β, IL-6, TNF-α, MPO, and PGE2). Notable downregulation of mRNA expression of p38 MAPK and increased protein expression of TGF-β were achieved by BER treatment. The anti-inflammatory potential of BER was supported by the histopathological screening of colon mucosa. In addition, BER restored colonic antioxidant capacity through elevation of GSH level and antioxidant enzymatic activities (SOD, CAT, GPx, and GR) together with reductions of both MDA and NO levels. Marked downregulation of Nos2 mRNA expression is accompanied by increased Nrf2 and Hmox-1 expressions in colon specimens treated by BER. Furthermore, BER exhibited noticeable antiapoptotic activities through decreasing proapoptotic proteins (Bax and caspase-3) and lessening antiapoptotic Bcl-2 protein in the colon mucosa. Based on these findings, BER may improve colitis markedly which may be mediated by its striking antioxidant, anti-inflammatory, and antiapoptotic properties.

High-mobility group box 1 (HMGB1) in COVID-19: extrapolation of dangerous liaisons

“…Initiation of ALI is started when extracellular HMGB1 activates cell membrane TLR2, TLR4 and RAGE receptors. Activation of RAGE receptors leads to triggering of ROS-dependent activation of MAPK pathway (Al-Kuraishy et al 2021c ; Jia et al 2020 ). Though, activations of TLR2 and TLR4 by HMGB1 trigger activations of intracellular myeloid differentiation 88 (MyD88), which activates inhibitor of nuclear factor kappa B kinase (IKK-β) (Al-Kuraishy et al 2021c ).…”

Saccharomyces boulardii Ameliorates Dextran Sulfate Sodium‐Induced Ulcerative Colitis in Mice by Regulating NF‐κB and Nrf2 Signaling Pathways

“…Remarkably, nuclear transcription factor kappa B (NF- κ B), a key regulatory component in inflammatory process, has been found to be observably activated in UC patients and strongly affects the progression of mucosal inflammation [ 10 ]. Moreover, as one of the pivotal transcription factors against inflammation and oxidative stress, nuclear factor erythroid 2-related factor 2 (Nrf2) is reported to be implicated in the suppression of proinflammatory signaling and inflammation-associated pathogenesis [ 11 , 12 ]. In this regard, it is likely that NF- κ B and Nrf2 signaling pathways are promising targets for the molecular therapy of UC.…”

Based on Network Pharmacology to Explore the Active Ingredients and Molecular Targets of Zuojin Pill for the Treatment of Ulcerative Colitis

“…ZJP is composed of Coptis chinensis and Evodia rutaecarpa, which has the material basis for the treatment of UC. For example, berberine inhibited p38 MAPK signaling pathway and decreased the levels of in ammatory biomarkers IL-1,TNF-α and IL-6 in UC [13] ; rutaecarpine inhibited KEAP1-NRF2…”

“…ZJP is composed of Coptis chinensis and Evodia rutaecarpa, which has the material basis for the treatment of UC. For example, berberine inhibited p38 MAPK signaling pathway and decreased the levels of in ammatory biomarkers IL-1,TNF-α and IL-6 in UC [13] ; rutaecarpine inhibited KEAP1-NRF2 interaction to activate NRF2 and ameliorate dextran sulfate sodium-induced colitis [14] .However, as a traditional Chinese medicine compound, the mechanism of ZJP on UC is not clear, and other effective components are still worth exploring. In this study, we successfully identi ed 7 active molecules and 3 important pathways related to UC through network pharmacology and bioinformatics.…”