title: Bergenin decreases the morphine-induced physical dependence via antioxidative activity in mice.
abstract: Oxidative stress plays a role in the development of physical dependence induced by morphine. Bergenin, a polyphenol found in many Asian, African, and South American medicinal plants, is a potent antinarcotic agent with wide spectrum of pharmacological activities including antioxidant action. In the present study, we observed that bergenin decreased the development of physical dependence induced by morphine in mice and the antioxidant activity of bergenin plays a role in the antinarcotic effects through adapting to morphine-induced oxidative stress in the brain. The naloxone-precipitated withdrawal symptom (jumping frequency) was significantly ameliorated (50% of control group) by administration of bergenin (20 mg/kg) in morphine-treated mice. Furthermore, morphine-induced down-regulation of glutathione (GSH) contents was reversed by bergenin administration in the frontal cortex and liver. Bergenin had no effects on the increased levels of nfr2-dependent antioxidant enzyme HO1 and NQO1 in the frontal cortex, striatum, and liver of morphine-treated mice. However, the morphine-induced increase in nrf2 nuclear translocation in the frontal cortex and striatum was inhibited by bergenin treatment. These results suggest that bergenin has a potential antinarcotic effect via regulation of GSH contents and oxidative stress.
authors.affiliation: Pharmacological Research Division, Ministry of Food and Drug Safety, Cheongju, 363-700, Republic of Korea.
authors.forename: Jaesuk
authors.initials: J
authors.lastname: Yun
authors.forename: Yeonju
authors.initials: Y
authors.lastname: Lee
authors.forename: Kyunghwa
authors.initials: K
authors.lastname: Yun
authors.forename: Seikwan
authors.initials: S
authors.lastname: Oh
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001578:Benzopyrans / Q000627:therapeutic use*; D005978:Glutathione / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009021:Morphine Dependence / Q000188:drug therapy* / Q000523:psychology; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy; D014178:Translocation, Genetic / Q000187:drug effects
chemical_list: D000975:Antioxidants; D001578:Benzopyrans; D051267:NF-E2-Related Factor 2; D009292:Narcotic Antagonists; C495636:Nfe2l2 protein, mouse; D009270:Naloxone; D051547:Heme Oxygenase-1; D005978:Glutathione; C006741:bergenin