Inhibition of hematopoietic prostaglandin D2 Synthase (H-PGDS) by an alkaloid extract from Combretum molle

BMC Complementary and Alternative Medicine

Stanley Mukanganyama¹  Theresa Chimponda²  Rejoice Moyo³ 

[1] Biomolecular Interactions Analyses Group, Department of Biochemistry, University of Zimbabwe, P.O. Box MP 167, Mt. Pleasant, Harare, Zimbabwe;Department of Biochemistry, University of Zimbabwe, Mt. Pleasant, Harare, Zimbabwe;School of Pharmacy, College of Health Sciences, University of Zimbabwe, Mt. Pleasant, Harare, Zimbabwe

关键词: Hematopoietic prostaglandin D₂ synthase;    Alkaloid;    Combretum molle;   

Others  :  1087471
DOI  :  10.1186/1472-6882-14-221

 received in 2014-02-06, accepted in 2014-06-30,  发布年份 2014

【 摘 要 】

Background

Hematopoietic prostaglandin D₂ synthase (H-PGDS, GST Sigma) is a member of the glutathione S-transferase super family of enzymes that catalyses the conjugation of electrophilic substances with reduced glutathione. The enzyme catalyses the conversion of PGH₂ to PGD₂ which mediates inflammatory responses. The inhibition of H-PGDS is of importance in alleviating damage to tissues due to unwarranted synthesis of PGD₂. Combretum molle has been used in African ethno medicinal practices and has been shown to reduce fever and pain. The effect of C. molle alkaloid extract on H-PGDS was thus, investigated.

Methods

H-PGDS was expressed in Escherichia coli XL1-Blue cells and purified using nickel immobilized metal affinity chromatography. The effect of C. molle alkaloid extract on H-PGDS activity was determined with 1-chloro-2, 4-dinitrobenzene (CDNB) as substrate. The effect of C. molle alkaloid extract with time on H-PGDS was determined. The mechanism of inhibition was then investigated using CDNB and glutathione (GSH) as substrates.

Results

A specific activity of 24 μmol/mg/min was obtained after H-PGDS had been purified. The alkaloid extract exhibited a 70% inhibition on H-PGDS with an IC₅₀ of 13.7 μg/ml. C. molle alkaloid extract showed an uncompetitive inhibition of H-PGDS with K_i = 41 μg/ml towards GSH, and non-competitive inhibition towards CDNB with K_i = 7.7 μg/ml and K_i^′ = 9.2 μg/ml.

Conclusion

The data shows that C. molle alkaloid extract is a potent inhibitor of H-PGDS. This study thus supports the traditional use of the plant for inflammation.

【 授权许可】

   
2014 Moyo et al.; licensee BioMed Central Ltd.

【 图 表 】

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