Beneficial Metabolic Effects of 2′,3′,5′-tri-acetyl-N(6)- (3-Hydroxylaniline) Adenosine in the Liver and Plasma of Hyperlipidemic Hamsters

BACKGROUND: Pharmaceutical research of hyperlipidemia has been commonly pursued using traditional approaches. However, unbiased metabonomics attempts to explore the metabolic signature of hyperlipidemia in a high-throughput manner to understand pathophysiology of the disease process. METHODOLOGY/PRINCIPAL FINDINGS: As a new way, we performed (1)H NMR-based metabonomics to evaluate the beneficial effects of 2′,3′,5′-tri-acetyl-N(6)- (3-hydroxylaniline) adenosine (WS070117) on plasma and liver from hyperlipidemic Syrian golden hamsters. Both plasma and liver profiles provided a clearer distinction between the control and hyperlipidemic hamsters. Compared to control animals, hyperlipidemic hamsters showed a higher content of lipids (triglyceride and cholesterol), lactate and alanine together with a lower content of choline-containing compounds (e.g., phosphocholine, phosphatidylcholine, and glycerophosphocholine) and betaine. As a result, metabonomics-based findings such as the PCA and OPLS-DA plotting of metabolic state and analysis of potential biomarkers in plasma and liver correlated well to the assessment of biochemical assays, Oil Red O staining and in vivo ultrasonographic imaging suggesting that WS070117 was able to regulate lipid content and displayed more beneficial effects on plasma and liver than simvastatin. CONCLUSIONS/SIGNIFICANCE: This work demonstrates the promise of applying (1)H NMR metabonomics to evaluate the beneficial effects of WS070117 which may be a good drug candidate for hyperlipidemia.