title: Morin sulfates/glucuronides exert anti-inflammatory activity on activated macrophages and decreased the incidence of septic shock.
abstract: Morin is a flavonoid present in fruits and Chinese herbs. Based on in vitro studies, morin has been reported to show various beneficial biological activities. However, there is growing evidence that conjugative metabolism is central to the biological fate of flavonoids. Therefore, the biological effects of morin could be primarily determined by its conjugated metabolites. In this study, the effects of morin and its sulfates/glucuronides on the production of nitric oxide (NO) and cytokines from lipopolysaccharide (LPS)-activated macrophages were individually investigated and compared. The results indicated that the 50% NO production was inhibited from LPS-activated RAW 264.7 cells by 1.25 mM morin and 1.25 microM morin sulfates/glucuronides. Meanwhile, the 50% inhibition concentration (IC50) values of morin and morin sulfates/glucuronides in activated peritoneal macrophages were 1.5 mM morin and 1.5 microM morin sulfates/glucuronides, respectively. In addition, 30% of the tumor necrosis factor-alpha (TNF-alpha) and 35% of the interleukin (IL)-12 productions from activated macrophages were inhibited by 2-2.5 mM morin and 2-2.5 microM morin sulfates/glucuronides, respectively. Furthermore, phagocyte activities in the peripheral blood of those for mice dosed with morin for two months were about 65-70% of controls. Lower NO production and reduced macrophage phagocytic activities corresponded to LPS-resistant state. These findings indicated that morin may exhibit anti-inflammatory activity and reduced the incidence of experimental septic shock through decreasing the functions of macrophages and may regulate immune response through modulating the cytokine profiles. Therefore, morin could be a promising therapeutic candidate for inflammatory disease due to the strong activity of its metabolites.
authors.affiliation: Department of Microbiology, School of Medicine, China Medical University, Taichung 404, Taiwan. shfang@mail.cmu.edu.tw
authors.forename: Shih-Hua
authors.initials: SH
authors.lastname: Fang
authors.forename: Yu-Chi
authors.initials: YC
authors.lastname: Hou
authors.forename: Weng-Cheng
authors.initials: WC
authors.lastname: Chang
authors.forename: Su-Lan
authors.initials: SL
authors.lastname: Hsiu
authors.forename: Pei-Dawn Lee
authors.initials: PD
authors.lastname: Chao
authors.forename: Bor-Luen
authors.initials: BL
authors.lastname: Chiang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D002460:Cell Line; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal; D005419:Flavonoids / Q000378:metabolism / Q000494:pharmacology*; D020719:Glucuronides / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D018664:Interleukin-12 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000378:metabolism; D010586:Phagocytes / Q000187:drug effects; D012772:Shock, Septic / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D013431:Sulfates / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D047309:Flavones
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D004365:Drugs, Chinese Herbal; D005419:Flavonoids; D020719:Glucuronides; D018664:Interleukin-12; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D013431:Sulfates; D014409:Tumor Necrosis Factor-alpha; C008548:morin; D047309:Flavones