MESUAFERRIN A-BIOACTIVE FLAVONOID ISOLATED FROM THE BARK OF MESUA FERREA L. AGAINST PHOSPHOLIPASE A2, CYCLOOXYGENASE AND LIPOXYGENASE: AN IN VITRO, IN VIVO AND IN SILICO APPROACH


Krishna Chaithanya K., Gopalakrishnan V. K., Zenebe Hagos, Govinda Rao D.

Abstract


Objective: The main objective of the present study was to evaluate the anti-inflammatory activity of isolated bioactive flavonoid Mesuaferrin-A from the bark of Mesuaferrea L. by in vitro, in vivo and in silico approach.

Methods: To evaluate the effect of isolated bioactive flavonoid Mesuaferrin-A on arachidonic acid metabolizing enzymes (PLA2, COX-2 and 5-LOX) using in vitro methods, followed by carrageenan-induced paw edema model by in vivo and to determine the binding orientation and interactions of Mesuaferrin-A onarachidonic acid metabolizing enzymes (PLA2, COX-2 and 5-LOX) crystal proteins using molecular docking (in silico) studies.

Results: Mesuaferrin-A exhibited a dose-dependent significant 5-LOX inhibitory and considerable COX-2 inhibitory activity by in vitro, The inhibitory activities of 5-LOX and COX-2 at 100µg/ml were found to be 78.67%, 81.03% with IC50 values of 45.22µg/ml and 35.74µg/ml respectively. Whereas Mesuaferrin-A showed less PLA2 inhibitory activity. Mesuaferrin-A showed 68.34% inhibitory activity at 400 mg/kg body weight at the late phase of carrageenan-induced paw edema, and In silico studies demonstrated that Mesuaferrin-A strongly binds with 5-LOX and COX-2, these strong binding affinity of Mesuaferrin-A on active site amino acids of 5-LOX and COX-2 may be responsible for inhibition of enzyme activity. Mesuaferrin-A showeda comparable 5-LOX and COX-2 inhibition activity with (positive control).

Conclusion: It was concluded that Mesuaferrin-A act as 5-LOX and COX dual inhibitor, from the results it was suggests that Mesuaferrin-A, may be an effective preventive and therapeutic approach for patients with inflammatory-related diseases.


Keywords


Mesuaferrin-A, Phospholipase-A2(PLA2), 5-Lipooxygenase (5-LOX), Cyclooxygenase-2 (COX-2), Generic Evolutionary Method for molecular Docking (GEM Dock)

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About this article

Title

MESUAFERRIN A-BIOACTIVE FLAVONOID ISOLATED FROM THE BARK OF MESUA FERREA L. AGAINST PHOSPHOLIPASE A2, CYCLOOXYGENASE AND LIPOXYGENASE: AN IN VITRO, IN VIVO AND IN SILICO APPROACH

Keywords

Mesuaferrin-A, Phospholipase-A2(PLA2), 5-Lipooxygenase (5-LOX), Cyclooxygenase-2 (COX-2), Generic Evolutionary Method for molecular Docking (GEM Dock)

DOI

10.22159/ijpps.2018v10i2.23576

Date

01-02-2018

Additional Links

Manuscript Submission

Journal

International Journal of Pharmacy and Pharmaceutical Sciences
Vol 10, Issue 2, 2018 Page: 102-106

Online ISSN

0975-1491

Authors & Affiliations

Krishna Chaithanya K.
Department of Chemistry, College of Natural and Computational Sciences, Aksum University, Axum, Ethiopia
Ethiopia

Gopalakrishnan V. K.
Department of Chemistry, College of Natural and Computational Sciences, Aksum University, Axum, Ethiopia
Ethiopia

Zenebe Hagos
Department of Chemistry, College of Natural and Computational Sciences, Aksum University, Axum, Ethiopia
Ethiopia

Govinda Rao D.
Department of Biochemistry and Molecular Biology, School of Biological Sciences, Central University of Kerala, India
India


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