Inhibitory effects of flavonol glycosides from Cinnamomum osmophloeum on inflammatory mediators in LPS/IFN-gamma-activated murine macrophages.
Four kaempferol glycosides were isolated from the leaves of Cinnamomum osmophloeum Kaneh, a Taiwan endemic tree. These compounds namely, kaempferitrin (1), kaempferol 3-O-beta-D-glucopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-7-O-alpha-L-rhamnopyranoside (2), kaempferol 3-O-beta-D-apiofuranosyl-(1-->2)-alpha-L-arabinofuranosyl-7-O-alpha-L-rhamnopyranoside (3), and kaempferol 3-O-beta-D-apiofuranosy-(1-->4)-alpha-L-rhamnopyranosyl-7-O-alpha-L-rhamnopyranoside (4). The structure of compound 2 was determined by spectroscopic analyses and acid hydrolysis. The isolates 1-4 were evaluated as inhibitors of some macrophage functions involved in the inflammatory process. These four compounds inhibited lipopolysaccharide (LPS) and interferon (IFN)-gamma-induced nitric oxide (NO), and cytokines [tumor necrosis factor (TNF)-alpha and interleukin (IL)-12] in a dose-dependent manner. The concentration of 50% inhibition (IC(50)) of NO by compounds 1, 3, 4 were 40, 15, 20microM, respectively. In parallel, these concentrations were approximately in a similar manner to that observed for TNF-alpha and IL-12 production. However, compound 2 inhibited NO and cytokines production by 30% at 100microM concentration. On the other hand, compounds 3 and 4 showed no inhibitory effect on the production of NO from macrophages, when inducible NO synthase was already expressed by the stimulation with LPS and IFN-gamma. Taken together, our results provide evidence that isolates of C. osmophloeum possess an anti-inflammatory potential which constitutes a previously unrecognized biological activity.
Fang
Shih-Hua
SH
Department of Microbiology, School of Medicine, China Medical University, Taichung 400, Taiwan, ROC.
Rao
Yerra Koteswara
YK
Tzeng
Yew-Min
YM
D000818:Animals; D002236:Carbohydrate Conformation; D027424:Cinnamomum / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D005260:Female; D044948:Flavonols / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006027:Glycosides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors*; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000494:pharmacology; D018664:Interleukin-12 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000187:drug effects; D018515:Plant Leaves / Q000737:chemistry; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D044948:Flavonols; D006027:Glycosides; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D009569:Nitric Oxide; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase