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

  • Original Research Paper
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Inflammation Research Aims and scope Submit manuscript

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 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.

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Abbreviations

NO:

Nitric oxide

PGE2 :

Prostaglandin E2

TNF-α:

Tumour necrosis factor-α

LPS:

Lipopolysaccharide

IC50 :

Inhibitory concentration 50

DMSO:

Dimethyl sulfoxide

DMEM:

Dulbecco’s modified eagle media

MTT:

3-[4, 5-Dimethyl-2-thiazolyl]-2,5-diphenyl tetrazolium bromide

FBS:

Foetal bovine serum

L-NAME:

N-nitro-l-arginine methyl ester

MRSA:

Methicillin-resistant Staphylococcus aureus

MIC:

Minimal inhibitory concentration

EGCG:

Epigallocatechin gallate

NSAID:

Non-steroidal anti-inflammatory drug

MAPK:

Mitogen-activated protein kinase

IRF-1:

Interferon regulatory factor-1

ERK:

Extracellular-regulated kinase

JNK:

c-Jun N-terminal kinase

LDL:

Low density lipoprotein

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Acknowledgments

We thank Zulkhairi Zainol, Abdul Rahman Hassan and Nora Asyikin Mohd Salim for technical assistance. This investigation was financially supported by Science Fund (06-01-04-SF0973), Ministry of Science, Technology and Innovation, Malaysia.

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Authors and Affiliations

  1. Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia

    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

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  1. Omar A. Harasstani
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Correspondence to Daud A. Israf.

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Responsible Editor: J. Skotnicki.

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Harasstani, O.A., Moin, S., Tham, C.L. et al. Flavonoid combinations cause synergistic inhibition of proinflammatory mediator secretion from lipopolysaccharide-induced RAW 264.7 cells. Inflamm. Res. 59, 711–721 (2010). https://doi.org/10.1007/s00011-010-0182-8

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  • DOI: https://doi.org/10.1007/s00011-010-0182-8

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