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Protective Effect of Dietary Tocotrienols against Infection and Inflammation‐induced Hyperlipidemia: An In Vivo and In Silico Study
Author(s) -
Salman Khan M.,
Akhtar Salman,
AlSagair Othman A.,
Arif Jamal M.
Publication year - 2011
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.3448
Subject(s) - atorvastatin , fluvastatin , hyperlipidemia , hmg coa reductase , pharmacology , reductase , hydroxymethylglutaryl coa reductase , cholesterol , chemistry , inflammation , apolipoprotein b , medicine , enzyme , biochemistry , endocrinology , simvastatin , diabetes mellitus
Currently used hypolipidemic drugs, Fluvastatin and Atorvastatin, act via inhibiting the rate‐limiting enzyme 3‐hydroxy‐3‐methyl‐glutaryl‐coenzyme A (HMG‐CoA) reductase of the mevalonate pathway. The associated severe side‐effects of these statins led us to explore the therapeutic potentials of naturally occurring Tocomin (mixture of dietary α‐, β‐, γ‐ and δ‐tocotrienols). Tocomin (10 mg) was orally administered daily for 10 days before and 12 h after bacterial lipopolysaccharide (200 μg) or 24 h after zymosan (20 mg) or turpentine (0.5 mL) to Syrian hamsters. The data showed that Tocomin significantly reduced the levels of plasma and lipoprotein lipids, cholesterol, apoB, small dense (sd)‐LDL as well as LDL in the hyperlipidemia‐induced hamsters. Further, the mechanism of action of α‐, β‐, γ‐ and δ‐tocotrienols was validated by docking studies with HMG‐CoA reductase enzyme using the Molegro Virtual Docker. The inhibition of HMG‐CoA reductase predicted in terms of MolDockScore and interaction energy suggest the comparative potential in the descending order: Atorvastatin > Fluvastatin ~ δ > γ > β > α. The results favor the daily intake of naturally occurring tocotrienols as dietary supplement in the prevention and treatment of infection/inflammation induced dyslipidemia compared with the hypolipidemic drugs. Copyright © 2011 John Wiley & Sons, Ltd.