title: Flavonoid combinations cause synergistic inhibition of proinflammatory mediator secretion from lipopolysaccharide-induced RAW 264.7 cells.
abstract: OBJECTIVE
  We evaluated several flavonoid combinations for synergy in the inhibition of proinflammatory mediator synthesis in the RAW 264.7 cellular model of inflammation.
  
  
  METHODS
  The inhibitory effect of chrysin, kaempferol, morin, silibinin, quercetin, diosmin and hesperidin upon nitric oxide (NO), prostaglandin E(2) (PGE(2)) and tumour necrosis factor-alpha (TNF-alpha) secretion from the LPS-induced RAW 264.7 monocytic macrophage was assessed and IC(50) values obtained. Flavonoids that showed reasonable inhibitory effects in at least two out of the three assays were combined in a series of fixed IC(50) ratios and reassessed for inhibition of NO, PGE(2) and TNF-alpha. Dose-response curves were generated and interactions were analysed using isobolographic analysis.
  
  
  RESULTS
  The experiments showed that only chrysin, kaempferol, morin, and silibinin were potent enough to produce dose-response effects upon at least two out of the three mediators assayed. Combinations of these four flavonoids showed that several combinations afforded highly significant synergistic effects.
  
  
  CONCLUSIONS
  Some flavonoids are synergistic in their anti-inflammatory effects when combined. In particular chrysin and kaempferol significantly synergised in their inhibitory effect upon NO, PGE(2) and TNF-alpha secretion. These findings open further avenues of research into combinatorial therapeutics of inflammatory-related diseases and the pharmacology of flavonoid synergy.
authors.affiliation: Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia.
authors.forename: Omar A
authors.initials: OA
authors.lastname: Harasstani
authors.forename: Saidi
authors.initials: S
authors.lastname: Moin
authors.forename: Chau Ling
authors.initials: CL
authors.lastname: Tham
authors.forename: Choi Yi
authors.initials: CY
authors.lastname: Liew
authors.forename: Norazren
authors.initials: N
authors.lastname: Ismail
authors.forename: Revathee
authors.initials: R
authors.lastname: Rajajendram
authors.forename: Hanis H
authors.initials: HH
authors.lastname: Harith
authors.forename: Zainul A
authors.initials: ZA
authors.lastname: Zakaria
authors.forename: Azam S
authors.initials: AS
authors.lastname: Mohamad
authors.forename: Mohamad R
authors.initials: MR
authors.lastname: Sulaiman
authors.forename: Daud A
authors.initials: DA
authors.lastname: Israf
mesh_terms: D000818:Animals; D002460:Cell Line; D015232:Dinoprostone / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005419:Flavonoids / Q000494:pharmacology* / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000633:toxicity; D008264:Macrophages / Q000187:drug effects*; D051379:Mice; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D005419:Flavonoids; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D015232:Dinoprostone