title: Induction of heme oxygenase-1 by Macleaya cordata extract and its constituent sanguinarine in RAW264.7 cells.
abstract: Macleaya cordata (plume poppy) is used in traditional Chinese medicine for its anti-inflammatory and antibacterial activities. In this study, we examined whether M. cordata extract and/or its major alkaloid constituents, protopine, allocryptopine, sanguinarine and chelerythrine activate the Nrf2 signalling pathway which regulates the expression of cytoprotective enzymes including heme oxygenase-1 (HO-1) and thioredoxin 1. In murine macrophage RAW264.7 cells, M. cordata extract increased both mRNA and protein levels of HO-1. Of the alkaloids examined, only sanguinarine appeared to be responsible for these effects. At the concentration of 2 μM, sanguinarine induced nuclear accumulation of Nrf2, increased the expression of Hmox1 gene encoding HO-1 and elevated HO-1 protein levels. Sanguinarine-induced Hmox1 mRNA expression was suppressed by SB203580, a pharmacologic inhibitor of p38 mitogen-activated protein kinases (p38 MAPKs). The upregulation of HO-1 in RAW264.7 cells by sanguinarine was, however, accompanied by decrease in cell viability. Nonetheless, sanguinarine at micromolar, non-cytotoxic concentrations elevated protein levels of HO-1 and thioredoxin 1 in primary cultures of human hepatocytes. We conclude that sanguinarine may, under appropriate conditions, increase the capacity of the enzymatic antioxidant defence system via activation of the p38 MAPK/Nrf2 pathway.
authors.affiliation: Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic. vrbambv@seznam.cz
authors.forename: Jiri
authors.initials: J
authors.lastname: Vrba
authors.forename: Eva
authors.initials: E
authors.lastname: Orolinova
authors.forename: Jitka
authors.initials: J
authors.lastname: Ulrichova
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D053119:Benzophenanthridines / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D051547:Heme Oxygenase-1 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D022781:Hepatocytes / Q000201:enzymology; D006801:Humans; D007546:Isoquinolines / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D008516:Medicine, Chinese Traditional; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D028101:Papaveraceae / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry; D012333:RNA, Messenger / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D013879:Thioredoxins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000470:Alkaloids; D000975:Antioxidants; D053119:Benzophenanthridines; D007546:Isoquinolines; D051267:NF-E2-Related Factor 2; D010936:Plant Extracts; D012333:RNA, Messenger; D013879:Thioredoxins; C005705:sanguinarine; D051547:Heme Oxygenase-1