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Protective effect of coptisine free base on indomethacin-induced gastric ulcers in rats: Characterization of potential molecular mechanisms

Luo, Chaodan, Chen, Hanbin, Wang, Yongfu, Lin, Guosheng, Li, Cailan, Tan, Lihua, Su, Ziren, Lai, Xiaoping, Xie, Jianhui, Zeng, Huifang
Life sciences 2018 v.193 pp. 47-56
angiotensin II, animal models, anti-ulcer activity, antioxidants, berberine, cytosol, enzyme-linked immunosorbent assay, glutathione, heme oxygenase (biliverdin-producing), indomethacin, ingestion, interleukin-1beta, lansoprazole, malondialdehyde, messenger RNA, mitogen-activated protein kinase, myeloperoxidase, prostaglandin synthase, prostaglandins, protective effect, quantitative polymerase chain reaction, rats, reverse transcriptase polymerase chain reaction, signal transduction, stomach ulcers, superoxide dismutase, tumor necrosis factor-alpha
The aim of this study was to comparatively investigate the potential gastroprotective effect and underlying mechanisms of coptisine free base (CFB, 8-hydroxy-7, 8-dihydrocoptisine), berberine and lansoprazole against indomethacin-induced gastric ulcer in rats.CFB (10, 20 and 40mg/kg), berberine (20mg/kg) and lansoprazole (30mg/kg) were orally administrated to rats prior to indometacin ingestion, and gastric lesions were evaluated macroscopically and histologically, and further analyzed by ELISA, qRT-PCR and Western blot.CFB exerted comparable or superior gastroprotective effect to berberine in protecting against indomethacin-induced gastric injury. CFB pretreatment significantly enhanced the levels of superoxide dismutase (SOD) and glutathione (GSH), and markedly decreased the malonaldehyde (MDA) content. CFB administration effectively suppressed the levels of myeloperoxidase (MPO), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and angiotensin II (Ang II). Besides, CFB substantially up-regulated the mRNA expressions of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), and promoted gastric mucosal prostaglandin E2 level (PGE2). Furthermore, CFB pretreatment remarkably increased the translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) from cytosol into the nucleus, and the expression of heme oxygenase-1 (HO-1), while significantly decreased the expression of mitogen activated protein Kinase Kinase 6 (MKK6) and translocation of p38 mitogen-activated protein kinase (p38 MAPK).This was the first investigation reporting the anti-ulcer effect of protoberberine alkaloid free base on in vivo rodent model. The gastroprotective mechanism of CFB might involve favorable regulation of antioxidant and anti-inflammatory status mediated, at least partially, by the Nrf2 signaling pathway and p38 MAPK translocation.