Abstract
Aim:
To investigate the protective effects of berberine on ethanol-induced gastric ulcer in mice.
Methods:
Gastric ulcers were induced by oral ingestion of ethanol. Nitric oxide (NO) content was measured, and mRNA expression of endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) were analyzed by reverse transcription-polymerase chain reaction (RT-PCR).
Results:
The ulcer index (UI) at 1 h, 2 h, 3 h and 6 h after oral administration of ethanol was 23.8±1.4, 23.3±2.2, 22.3±1.2 and 20.8±1.1, respectively. The UI in the berberine-treated groups (5 mg/kg and 50 mg/kg) was less than the control group. The content of NO in the control group was 73.3±7.3 μL/L, 94.0±9.2 μL/L, 109.6± 6.4 μL/L and 138.2±10.2 μL/L in gastric juice and 5.8±1.1 μmol/g protein, 8.3± 1.1 μmol/g protein, 9.8± 1.1 μmol/g protein and 11.9± 1.2 μmol/g protein in gastric tissue at 1 h, 2 h, 3 h and 6 h, respectively, after the oral administration of ethanol. The content of NO in the berberine-treated groups (5 mg/kg and 50 mg/kg) was higher than the control group at 1 h after the oral administration of ethanol (P<0.05), and was lower at 6 h (P<0.05). Analysis by RT-PCR showed that expression of eNOS was inhibited but iNOS expression was enhanced by ethanol. However, the expression of eNOS could be enhanced and iNOS expression could be inhibited by berberine (P<0.01).
Conclusion:
Berberine could significantly protect gastric mucosa from damage by ethanol. This effect may be related to the increased expression of eNOS mRNA and inhibited expression of iNOS mRNA.
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Pan JF, Yu C, Zhu DY, Zhang H, Zeng JF, Jiang SH, et al. Identification of three sulfate-conjugated metabolites of berberine chloride in healthy volunteers' urine after oral administration. Acta Pharmacol Sin 2002; 23: 77–82.
Hicano H . Protective effects of Huanglian on gastric mucosa. Foreign Med Sci 1998; 20: 31.
Luo JD, Chen AF . Nitric oxide: a newly discovered function on wound healing. Acta Pharmacol Sin 2005; 26: 259–64.
Ma L, Wallace JL . Endothelial nitric oxide synthase modulates gastric ulcer healing in rats. Am J Physiol Gastrointest Liver Physiol 2000; 279: 341–6.
Cho CH . Current roles of nitric oxide in gastrointenstinal disorders. J Physiol Paris 2001; 95: 253–6.
Kang DG, Sohn EJ, Kwon EK, Han JH, Oh H, Lee HS . Effects of berberine on angiotensin-converting enzyme and NO/cGMP system in vessels. Vascul Pharmacol 2002; 39: 281–6.
Lee DU, Kang YJ, Park MK, Lee YS, Seo HG, Kim TS, et al. Effects of 13-alkyl-substituted berberine alkaloids on the expression of COX-II, TNF-α, iNOS, and IL-12 production in LPS-stimulated macrophages. Life Sci 2003; 73: 1401–12.
Jimenez D, Martin MJ, Pozo D, Alarcon C, Md JE, Bruseghini L, et al. Mechanisms involved in protection afforded by L-arginine in ibuprofen-induced gastric damage: role of nitric oxide and prostaglandins. Dig Dis Sci 2002; 47: 44–53.
Qureshi MA, Darzi A, Leahy AL, Bouchier-Hayes DJ . Transient reduction in gastric acid secretion following gastric mucosal laser irradiation. Surg Laparosc Endosc 1998; 8: 356–9.
Laufs U, Gertz K, Dirnagl U, Bohm M, Nickenig G, Endres M . Rosuvastatin, a new HMG-CoA reductase inhibitor, upregulates endothelial nitric oxide synthase and protects from ischemic stroke in mice. Brain Res 2002; 942: 23–30.
Garhart CA, Heinzel FP, Czinn SJ, Nedrud JG . Vaccine-induced reduction of Helicobacter pylori colonization in mice is interleukin-12 dependent but gamma interferon and inducible nitric oxide synthase independent. Infect Immun 2003; 71: 910–21.
Ma L, Wallace JL . Endothelial nitric oxide synthase modulates gastric ulcer healing in rats. Am J Physiol Gastrointest Liver Physiol 2000; 279: 341–6.
Ma JJ, Li SA . Nitric oxide and gastric ulcer. Prog Physiol Sci 1998; 29: 260–1.
Nishida K, Ohta Y, Ishiguro I . Role of gastric mucosal constitutive and inducible nitric oxide synthases in the development of stress-induced gastric mucosal lesions in rats. Biochem Biophys Res Commun 1997; 236: 275–9.
Qiu BS, Pfeiffer CJ, Cho CH . Effects of chronic nitric oxide synthase inhibition in cold-restraint and ethanol-induced gastric mucosal damage in rats. Digestion 1996; 57: 60–6.
Tepperman BL, Soper BD . Nitric oxide synthase induction and cytoprotection of rat gastric mucosa from injury by ethanol. Can J Physiol Pharmacol 1994; 72: 1308–12.
Zhang GF, Zhang MA, Chen YR, Wang L . The roles of endothelin and nitric oxide in gastric mucosa injuries in rats with endotoxemia. World Chin J Digestol 2000; 8 Suppl 8: 24.
Fischer H, Becker JC, Boknik P, Huber V, Lüss H, Neumann J, et al. Expression of constitutive nitric oxide synthase in rat and human gastrointestinal tract. Biochim Biophys Acta 1999; 1450: 414–22.
Li Y, Wang WP, Wang HY, Cho CH . Intragastric administration of heparin enhances gastric ulcer healing through a nitric oxide-dependent mechanism in rats. Eur J Pharmacol 2000; 399: 205–14.
Yu XE, Luo QN . Protective effects of exogenous nitric oxide on acid-ethanol induced gastric ulcer in guinea-pig. World Chin J Digestol 2000; 8: 224.
Ko WH, Yao XQ, Lau CW, Law WI, Chen ZY, Kwok W, et al. Vasorelaxant and antiproliferative effects of berberine. Eur J Pharmacol 2000; 399: 187–96.
Peng X, Feng JB, Wang SL, You ZY, Li A . Alterations of nitric oxide synthase and nitric oxide in gastric tissues of burned rats. World Chin J Digestol 1997; 5: 765–6.
Barrachina MD, Panes J, Esplugues JV . Role of nitric oxide in gastrointestinal inflammatory and ulcerative diseases: perspective for drugs development. Curr Pharm Des 2001; 7: 31–48.
Guo JS, Cho CH, Wang WH, Shen XZ, Cheng CL, Koo MW . Expression and activity patterns of three inducible enzymes in the healing of gastric ulcers in rats. Word J Gastroenterol 2003; 9: 1767–71.
Ding HL, Zhu HF, Dong JW, Zhu WZ, Yang WW, Yang HT, et al. Inducible nitric oxide synthase contributes to intermittent hypoxia against ischemia/reperfusion injury. Acta Pharmacol Sin 2005; 26: 315–22.
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Project supported by the National Natural Science Foundation of China, No 30171151.
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Pan, Lr., Tang, Q., Fu, Q. et al. Roles of nitric oxide in protective effect of berberine in ethanol-induced gastric ulcer mice. Acta Pharmacol Sin 26, 1334–1338 (2005). https://doi.org/10.1111/j.1745-7254.2005.00186.x
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DOI: https://doi.org/10.1111/j.1745-7254.2005.00186.x
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