Isolation and identification of two galangin metabolites from rat urine and determination of their in vitro hypolipidemic activity

Purpose: To investigate the lipid-lowering activity of two metabolites of galangin, namely, galangin-3-Oβ-D-glucuronic acid (GG-1) and galangin-7-O-β-D-glucuronic acid (GG-2). Methods: Female Sprague-Dawley rats were orally administered with galangin. The two metabolites of galangin were isolated from urine sample and purified using Sephadex LH-20 and semi-preparative high performance liquid chromatography (HPLC). The structures of the metabolites were identified by analyzing spectroscopic data. Hypolipidemic activity was evaluated in HepG2 cells. The down- or upregulation of lipogenic genes was detected using real-time quantitative polymerase chain reaction (qPCR). Results: Both metabolites of galangin showed hypolipidemic activity. These activities are closely associated with the down-regulation of lipogenic genes such as SREBP-1a, SREBP-1c, and SREBP-2 transcription factors, and the downstream genes such as FAS, ACC, and HMGR were revealed by realtime qPCR data. Conclusion: The results show that both metabolites possess better lipid-lowering activities than galangin. These hypolipidemic activities are closely associated with inhibiting key genes or proteins that regulated the biosynthesis of both cholesterol and triglycerides.

The influence of ApoE genotype on the lipid profile and lipoproteins during normal pregnancy in a Southern African population.

Background: Pregnancy is associated with increases in fasting triglycerides and total cholesterol.1 ApoE isoforms are known to influence the concentration of cholesterol, with apoE2 homozygosity lowering and apoE4 homozygosity raising the cholesterol concentration compared with E3 homozygosity.2 The lipid profiles ApoE status and prevalence of small dense LDL species were evaluated for subjects attending an antenatal clinic. Results: Samples from 690 women aged between 16 and 42 years of age were analyzed during and after pregnancy. The fasting plasma triglyceride concentration (in mmol/L) was significantly higher in pregnancy (median = 1.5, IQR 1.0-2.0 vs median = 0.6, IQR 0.5-0.8 respectively, p < 0.0001). Similarly, the total cholesterol (in mmol/L) was increased during pregnancy (median=4.1, IQR 3.6-4.7 vs median 3.5, IQR 3.1-3.5, respectively p=0.0167). The median LDL cholesterol and HDL cholesterol did not change. Higher proportions of small density LDL species were seen during pregnancy compared to after pregnancy. The distribution of the LDL species during pregnancy and 6 weeks post-partum were significantly different p<0.0001 with the smaller species being much higher during pregnancy. Conclusion: ApoE4 genotype was associated with increased total cholesterol and LDL cholesterol concentrations during pregnancy. Pregnancy results in a reversible remodeling of LDL to smaller species, the significance of which is unknown but may indicate a predisposition to atherosclerosis