Application of GC/MS-based metabonomic profiling in studying the lipid-regulating effects of Ginkgo biloba extract on diet-induced hyperlipidemia in rats

Abstract

Aim: To evaluate the lipid-regulating effects of extract from Ginkgo biloba leaves (EGB) using pharmacological methods and metabonomic profiling in a rat model of diet-induced hyperlipidemia. Methods: EGB was orally administered at a dose level of 40 mg/kg in both the EGB-prevention and -treatment groups. All rat samples obtained were examined for known and potential biomarkers and enzyme activity using commercial assay kits and GC/MS-based metabonomic profiling coupled with principal component analysis (PCA). Results: The data obtained from the assay kits indicated that EGB reduced total cholesterol and low density lipoprotein cholesterol levels and increased high density lipoprotein cholesterol levels in rat plasma obtained from both the EGB-prevention and -treatment groups compared with those of the diet-induced hyperlipidemia group. EGB also increased the activities of lipoprotein lipase and hepatic lipase and excretion of fecal bile acid in rats from the EGB-prevention and -treatment groups. Using GC/MS-based metabonomic analysis, more than 40 endogenous metabolites were identified in rat plasma. PCA of rat plasma samples obtained using GC/ MS produced a distinctive separation of the four treatment groups and sampling points within each group. Metabolic changes during hyperlipidemia formation and improvement resulting from EGB treatment were definitively monitored with PCA score plots. Furthermore, elevated levels of sorbitol, tyrosine, glutamine and glucose, and decreased levels of citric acid, galactose, palmitic acid, arachidonic acid, acetic acid, cholesterol, butyrate, creatinine, linoleate, ornithine and proline, were observed in the plasma of rats treated with EGB. Conclusion: EGB exerts multi-directional lipid-lowering effects on the rat metabonome, including limitation of the absorption of cholesterol, inactivation of HMGCoA and favorable regulation of profiles of essential polyunsaturated fatty acid (EFA). Further experiments are warranted to explore the mechanisms of action underlying the lipid-regulating effects of EGB against hyperlipidemia.

Ginkgo biloba extracts prevent aortic rupture in angiotensin II-infused hypercholesterolemic mice

“…It hypothesizes GBE in combination with statins helps to treat patients with hyperlipidemia, however, there is no randomized, control clinical trials to prove it. GBE administration has been shown to reduce serum total cholesterol concentration in dietinduced hyperlipidemia rats, mediated by limiting cholesterol absorption, inactivating 3-hydroxy-3-methylglutaryl-coenzyme A, and regulating polyunsaturated fatty acid [28]. In the present studies, GBE administration, for either 1 month or 3 months, did not reduce serum total cholesterol concentrations in apoE−/− mice.…”

Antihyperglycemic Effect ofGinkgo bilobaExtract in Streptozotocin-Induced Diabetes in Rats

“…Previous studies have demonstrated that GBE exerts multidirectional lipid-lowering effects on the rat metabonome, including limitation of the absorption of cholesterol, inactivation of HMG-CoA, and favorable regulation of profiles of essential polyunsaturated fatty acid [24]. In diabetes, hyperglycemia is accompanied with dyslipidemia [25] characterized by increase in TC, LDL, VLDL, and TG and fall in HDL.…”

GC-TOF/MS-based metabolomic profiling of estrogen deficiency-induced obesity in ovariectomized rats

“…As such, metabolomics has been comprehensively applied in physiology, disease, and toxicology research fields [26] . Nuclear magnetic resonance (NMR) spectroscopy [27] , liquid chromatography coupled mass spectrometry (LC-MS) [28] , gas chromatography coupled mass spectrometry (GC-MS) [29] , and Fourier transform mass spectrometry [30] have been successfully used to obtain metabolomic data. GC coupled to a time-of-flight mass analyzer (GC-TOF/ MS) provides an improvement over conventional GC-MS analysis due to its high scan rates and the availability of mathematic algorithms to deconvolute closely overlapping peaks.…”