Flavonoid combinations cause synergistic inhibition of proinflammatory mediator secretion from lipopolysaccharide-induced RAW 264.7 cells.

Objectives: 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...

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Main Authors: Harasstani, Omar A., Moin, Saidi, Tham, Chau Ling, Liew, Choi Yi, Ismail, Norazren A., Rajajendram, Revathee, Harith, Hanis Hazeera, Zakaria, Zainul Amiruddin, Tengku Mohamad, Tengku Azam Shah, Sulaiman, Mohd Roslan, Israf Ali, Daud Ahmad
Format: Article
Language:English
English
Published: Springer Verlag 2010
Online Access:http://psasir.upm.edu.my/id/eprint/14777/
http://psasir.upm.edu.my/id/eprint/14777/1/Flavonoid%20combinations%20cause%20synergistic%20inhibition%20of%20proinflammatory%20mediator%20secretion%20from%20lipopolysaccharide.pdf
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Summary:Objectives: 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 E2 (PGE2) and tumour necrosis factor-α (TNF-α) secretion from the LPS-induced RAW 264.7 monocytic macrophage was assessed and IC50 values obtained. Flavonoids that showed reasonable inhibitory effects in at least two out of the three assays were combined in a series of fixed IC50 ratios and reassessed for inhibition of NO, PGE2 and TNF-α. 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, PGE2 and TNF-α secretion. These findings open further avenues of research into combinatorial therapeutics of inflammatory-related diseases and the pharmacology of flavonoid synergy.