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. 2020 Sep 29:2020:9419085.
doi: 10.1155/2020/9419085. eCollection 2020.

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

Li Jia  1 , Kuijin Xue  2 , Junheng Liu  2 , Ola A Habotta  3 , Lianhai Hu  4 , Ahmed E Abdel Moneim  5
Affiliations

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

Li Jia et al. Mediators Inflamm. .

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.

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Conflict of interest statement

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1
Figure 1
Effect of berberine at different doses on experimental colitis in rats. (a) Macroscopic appearance of rat colon in experimental colitis. (b) Macroscopic score. (c) Histological score. The results are expressed as the mean ± SD (n = 7). #p < 0.05 compared to the CNTR group (intact group); $p < 0.05 compared to UC-untreated group.
Figure 2
Figure 2
Histological findings of the colon (H&E). (a) Colon from the CNTR group (intact group). (b) Colon from the BER group (without ulceration rats). (c) Colon in experimental colitis, untreated group; tissue injury is characterized by severe mucosal damage with severe hemorrhage and infiltration of inflammatory cells. (d) Colon in BER low dose (25 mg/kg) and experimental colitis, treated group, showing reduced tissue injury. (e) Colon in BER high dose (50 mg/kg) and experimental colitis, treated group, showing the greatest reduction in the tissue injury characterized by less mucosal damage and low infiltration of inflammatory cells. All the images were taken at a 200x magnification.
Figure 3
Figure 3
Effect of berberine at different doses on oxidative stress markers ((a) LPO, (b) GSH, and (c) NO) and (d) Nos2 mRNA expression in colonic tissue of experimental colitis in rats. The results are expressed as the mean ± SD (n = 7). qRT-PCR results of Nos2 were normalized with Gapdh and represented as fold change as compared to mRNA levels in the CNTR rats. #p < 0.05 compared to the CNTR group (intact group); $p < 0.05 compared to UC-untreated group.
Figure 4
Figure 4
Effect of berberine at different doses on antioxidant enzymes activity ((a) SOD, (b) CAT, (c) GPx, and (d) GR) in colonic tissue of experimental colitis in rats. The results are expressed as the mean ± SD (n = 7). #p < 0.05 compared to the CNTR group (intact group); $p < 0.05 compared to UC-untreated group.
Figure 5
Figure 5
Effect of berberine at different doses on (a) Nfe2l2 and (b) Hmox1 mRNA expression in colonic tissue of experimental colitis in rats. The results are expressed as the mean ± SD (n = 7). qRT-PCR results were normalized with Gapdh and represented as fold change as compared to mRNA levels in the CNTR rats. #p < 0.05 compared to the CNTR group (intact group); $p < 0.05 compared to UC-untreated group.
Figure 6
Figure 6
Effect of berberine at different doses on inflammatory mediators and cytokines ((a) PGE2, (b) TNF-α, (c) IL-1β, and (d) IL-6) and (e) Mapk14 mRNA expression in colonic tissue of experimental colitis in rats. The results are expressed as the mean ± SD (n = 7). qRT-PCR results of Mapk14 were normalized with Gapdh and represented as fold change as compared to mRNA levels in the CNTR rats. #p < 0.05 compared to the CNTR group (intact group); $p < 0.05 compared to UC-untreated group.
Figure 7
Figure 7
Effect of berberine at different doses on MPO activity in colonic tissue of experimental colitis in rats. The results are expressed as the mean ± SD (n = 7). #p < 0.05 compared to the CNTR group (intact group); $p < 0.05 compared to UC-untreated group.
Figure 8
Figure 8
Berberine supressing the protein expressions of TGF-β in colonic tissue of experimental colitis in rats. (a) Colon from the CNTR group (intact group). (b) Colon from the BER group (without ulceration rats). (c) Colon in experimental colitis, untreated group. (d) Colon in BER low dose (25 mg/kg) and experimental colitis, treated group. (e) Colon in BER high dose (50 mg/kg) and experimental colitis, treated group. All the images were taken at a 100x magnification.
Figure 9
Figure 9
Effect of berberine at different doses on apoptosis-related protein ((a) Bcl-2, (b) Bax, and (c) caspase-3) in colonic tissue of experimental colitis in rats. The results are expressed as the mean ± SD (n = 7). #p < 0.05 compared to the CNTR group (intact group); $p < 0.05 compared to UC-untreated group.
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