Chaodan Luo1, Hanbin Chen2, Yongfu Wang1, Guosheng Lin1, Cailan Li1, Lihua Tan1, Ziren Su1, Xiaoping Lai1, Jianhui Xie3, Huifang Zeng4. 1. Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China. 2. The First Affiliated Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, PR China. 3. Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510120, PR China. Electronic address: xiejianhui123@aliyun.com. 4. The First Affiliated Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, PR China. Electronic address: gancaozhf@126.com.
Abstract
AIMS: 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. MATERIALS AND METHODS: 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. KEY FINDINGS: 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). SIGNIFICANCE: 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.
AIMS: 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. MATERIALS AND METHODS: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. KEY FINDINGS: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 mucosalprostaglandin 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). SIGNIFICANCE: 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.
Authors: Amy Fakhry Boushra; Asmaa Mohammed Elsayed; Noha Abdellatif Ibrahim; Maha Khaled Abdelwahed; Eman Ibrahim Ahmed Journal: Mol Biol Rep Date: 2019-07-11 Impact factor: 2.316
Authors: Mohamed T Khayyal; Walaa Wadie; Enas A Abd El-Haleim; Kawkab A Ahmed; Olaf Kelber; Ramy M Ammar; Heba Abdel-Aziz Journal: World J Gastroenterol Date: 2019-10-21 Impact factor: 5.742