Diterpenoids from the seeds of Euphorbia lathyris and their effects on microglial nitric oxide production.

Four new lathyrane-type diterpenoids (1-4) and a novel macrocyclic diterpenoid (5) featuring a 5/7/7/4-fused ring system, together with seventeen known ones (6-22), were isolated from the seeds of Euphorbia lathyris. Their structures were elucidated by extensive spectroscopic analyses and single crystal X-ray crystallography. These isolates were evaluated for their inhibition against nitric oxide (NO) production induced by lipopolysaccharide (LPS) in BV-2 microglial cells. As a result, the inhibitory rates of compounds 1, 3, 4, 6, 7, 9-11, 13-15, 20, and 21 on NO production were more than 40% with the cell viability more than 80% at their effective concentrations. In addition, compounds 6 and 11 markedly reduced the mRNA levels of pro-inflammatory cytokines IL-6 and IL-1ß in LPS-stimulated BV-2 cells.

Inhibitory effect of Ginkgo biloba extract on fatty liver: regulation of carnitine palmitoyltransferase 1a and fatty acid metabolism.

OBJECTIVE: To investigate the potential effect of Ginkgo biloba extract (GBE) on the prevention and treatment of nonalcoholic fatty liver disease (NAFLD). METHODS: Male Wistar rats were divided into 4 groups (the control group, GBE group, high-fat diet [HFD] group and HFD + GBE group). The human hepatocellular carcinoma cell line (HepG2) was treated with GBE and its flavonoid ingredients. The fatty acid composition of the rat liver was analyzed with gas chromatography/time-of-flight mass spectrometry (GC/TOFMS). Triglyceride contents of both the rat liver and HepG2 cells were measured by enzymatic colorimetric method. The expressions of fatty acid metabolism-related genes were analyzed with real-time reverse transcription-polymerase chain reaction (RT-PCR). The protein expression and enzymatic activity were subsequently measured. RESULTS: In rat livers, GBE reduced the elevations of hepatic triglyceride contents caused by HFD and the increased hepatic fatty acids were differentially affected by GBE. Notably, the expression and total activity of the fatty acid ß-oxidation rate-limiting enzyme, carnitine palmitoyltransferase 1a (CPT1A), were also promoted with GBE ingestion. In HepG2 cells, GBE and its ingredients, quercetin, kaempferol and isorhamnetin, could decrease the cellular triglyceride content and upregulate the expression and total activity of CPT1A, respectively. CONCLUSIONS: The triglyceride-lowering effect of GBE on the HFD rat liver is closely associated with the increased expression and activity of CPT1A, and the flavonoid ingredients are the major contributors of GBE.

Molecular mechanisms underlying the cholesterol-lowering effect of Ginkgo biloba extract in hepatocytes: a comparative study with lovastatin.

AIM: To explore the molecular mechanisms underlying the cholesterol-lowering effect of a Ginkgo biloba extract (GBE). METHODS: Enzyme activity, cholesterol flux and changes in gene expression levels were assessed in cultured hepatocytes treated with GBE or lovastatin. RESULTS: GBE decreased the total cholesterol content in cultured hepatocytes and inhibited the activity of HMG-CoA reductase, as determined by an in vitro enzyme activity assay. In addition, GBE decreased cholesterol influx, whereas lovastatin increased cholesterol influx. GBE treatment induced significant increases in the expression of cholesterogenic genes and genes involved in cholesterol metabolism, such as SREBF2, as determined by cDNA microarray and real-time RT-PCR. Furthermore, INSIG2, LDLR, LRP1, and LRP10 were differentially regulated by GBE and lovastatin. The data imply that the two compounds modulate cholesterol metabolism through distinct mechanisms. CONCLUSION: By using a gene expression profiling approach, we were able to broaden the understanding of the molecular mechanisms by which GBE lowers cellular cholesterol levels. Specifically, we demonstrated that GBE exhibited dual effects on the cellular cholesterol pool by modulating both HMG-CoA reductase activity and inhibiting cholesterol influx.