Ascorbic acid 6-palmitate: a potent inhibitor of human and soybean lipoxygenase-dependent lipid peroxidation.
J Pharm Pharmacol
; 66(6): 769-78, 2014 Jun.
Article
in En
| MEDLINE
| ID: mdl-24359271
ABSTRACT
OBJECTIVES:
Lipoxygenases (LOX) are the key enzymes involved in the biosynthesis of leukotrienes and reactive oxygen species, which are implicated in pathophysiology of inflammatory disorders. This study was conducted to evaluate the inhibitory effect of water-soluble antioxidant ascorbic acid and its lipophilic derivative, ascorbic acid 6-palmitate (Vcpal) on polymorphonuclear lymphocyte 5-LOX and soybean 15-LOX (sLOX) in vitro.METHODS:
LOX activity was determined by measuring the end products, 5-hydroperoxy eicosatetraenoic acid (5-HETE) and lipid hydroperoxides, by spectrophotometric and high performance liquid chromatography methods. The substrate-dependent enzyme kinetics and docking studies were carried out to understand the nature of inhibition. KEYFINDINGS:
Vcpal potently inhibited 5-LOX when compared with its inhibitory effect on sLOX (IC50; 2.5 and 10.3 µm respectively, P = 0.003). Further, Vcpal inhibited 5-LOX more strongly than the known synthetic drugs phenidone and nordihydroguaiaretic acid (P = 0.0007). Enzyme kinetic studies demonstrated Vcpal as a non-competitive reversible inhibitor of 5-LOX. In-silico molecular docking revealed high MolDock and Rerank score for Vcpal than ascorbic acid, complementing in-vitro results.CONCLUSION:
Both in-vitro and docking studies demonstrated Vcpal but not ascorbic acid as a non-competitive inhibitor of 5-LOX- and sLOX-induced lipid peroxidation, suggesting a key role for lipophilic nature in bringing about inhibition.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Ascorbic Acid
/
Arachidonate 5-Lipoxygenase
/
Lipid Peroxidation
/
Antioxidants
Limits:
Humans
Language:
En
Journal:
J Pharm Pharmacol
Year:
2014
Document type:
Article
Affiliation country:
India