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

Abstract

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 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: Omar A Harasstani, Saidi Moin, Chau Ling Tham, Choi Yi Liew, Norazren Ismail, Revathee Rajajendram, Hanis H Harith, Zainul A Zakaria, Azam S Mohamad, Mohamad R Sulaiman, Daud A Israf
• Journal: Inflammation research : official journal of the European Histamine Research Society ... [et al.] (Inflamm Res) Vol. 59 Issue 9 Pg. 711-21 (Sep 2010) ISSN: 1420-908X [Electronic] Switzerland
• PMID: 20221843 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Flavonoids
• Lipopolysaccharides
• Tumor Necrosis Factor-alpha
• Nitric Oxide
• Dinoprostone

Topics

• Animals
• Cell Line
• Dinoprostone (antagonists & inhibitors, metabolism)
• Dose-Response Relationship, Drug
• Drug Synergism
• Flavonoids (pharmacology, therapeutic use)
• Inflammation (drug therapy, metabolism)
• Lipopolysaccharides (toxicity)
• Macrophages (drug effects)
• Mice
• Nitric Oxide (antagonists & inhibitors, metabolism)
• Tumor Necrosis Factor-alpha (antagonists & inhibitors, metabolism)