Ascorbic acid 6-palmitate

A potent inhibitor of human and soybean lipoxygenase-dependent lipid peroxidation

Riyaz Mohamed, Shaista Tarannum, Manjunath Yariswamy, Hamse K. Vivek, Jalahalli M. Siddesha, Nataraju Angaswamy, Bannikuppe S. Vishwanath

Research output: Contribution to journalArticle

7 Citations (Scopus)

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. Key findings Vcpal potently inhibited 5-LOX when compared with its inhibitory effect on sLOX (IC50; 2.5 and 10.3μm 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.

Original languageEnglish (US)
Pages (from-to)769-778
Number of pages10
JournalJournal of Pharmacy and Pharmacology
Volume66
Issue number6
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

Fingerprint

Lipoxygenase
Palmitates
Soybeans
Arachidonate 5-Lipoxygenase
Lipid Peroxidation
Ascorbic Acid
Lipoxygenases
Lipoxygenase Inhibitors
Enzymes
Arachidonate 15-Lipoxygenase
Masoprocol
Arachidonic Acids
Leukotrienes
Lipid Peroxides
Computer Simulation
Inhibitory Concentration 50
Reactive Oxygen Species
Antioxidants
High Pressure Liquid Chromatography
Lymphocytes

Keywords

  • ascorbic acid 6-palmitate
  • human
  • lipid peroxidation
  • lipoxygenase
  • soybean

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

Cite this

Mohamed, R., Tarannum, S., Yariswamy, M., Vivek, H. K., Siddesha, J. M., Angaswamy, N., & Vishwanath, B. S. (2014). Ascorbic acid 6-palmitate: A potent inhibitor of human and soybean lipoxygenase-dependent lipid peroxidation. Journal of Pharmacy and Pharmacology, 66(6), 769-778. https://doi.org/10.1111/jphp.12200

Ascorbic acid 6-palmitate : A potent inhibitor of human and soybean lipoxygenase-dependent lipid peroxidation. / Mohamed, Riyaz; Tarannum, Shaista; Yariswamy, Manjunath; Vivek, Hamse K.; Siddesha, Jalahalli M.; Angaswamy, Nataraju; Vishwanath, Bannikuppe S.

In: Journal of Pharmacy and Pharmacology, Vol. 66, No. 6, 01.01.2014, p. 769-778.

Research output: Contribution to journalArticle

Mohamed, R, Tarannum, S, Yariswamy, M, Vivek, HK, Siddesha, JM, Angaswamy, N & Vishwanath, BS 2014, 'Ascorbic acid 6-palmitate: A potent inhibitor of human and soybean lipoxygenase-dependent lipid peroxidation', Journal of Pharmacy and Pharmacology, vol. 66, no. 6, pp. 769-778. https://doi.org/10.1111/jphp.12200
Mohamed, Riyaz ; Tarannum, Shaista ; Yariswamy, Manjunath ; Vivek, Hamse K. ; Siddesha, Jalahalli M. ; Angaswamy, Nataraju ; Vishwanath, Bannikuppe S. / Ascorbic acid 6-palmitate : A potent inhibitor of human and soybean lipoxygenase-dependent lipid peroxidation. In: Journal of Pharmacy and Pharmacology. 2014 ; Vol. 66, No. 6. pp. 769-778.
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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. Key findings Vcpal potently inhibited 5-LOX when compared with its inhibitory effect on sLOX (IC50; 2.5 and 10.3μm 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.",
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T2 - A potent inhibitor of human and soybean lipoxygenase-dependent lipid peroxidation

AU - Mohamed, Riyaz

AU - Tarannum, Shaista

AU - Yariswamy, Manjunath

AU - Vivek, Hamse K.

AU - Siddesha, Jalahalli M.

AU - Angaswamy, Nataraju

AU - Vishwanath, Bannikuppe S.

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N2 - 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. Key findings Vcpal potently inhibited 5-LOX when compared with its inhibitory effect on sLOX (IC50; 2.5 and 10.3μm 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.

AB - 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. Key findings Vcpal potently inhibited 5-LOX when compared with its inhibitory effect on sLOX (IC50; 2.5 and 10.3μm 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.

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