Ginkgolides,the unique terpenoids in Ginkgo biloba,have a significant effect on the prevention and treatment of cardiovascular and cerebrovascular diseases. Metabolic regulation and synthetic biology strategies are efficient methods to obtain high-quality ginkgolides. The present study reviewed the cloning and functions of genes related to the biosynthetic pathway of ginkgolides,as well as relevant studies of omics,genetic transformation,and metabolic regulation in recent years,and predicted the research trends and prospects,aiming to provide a reference for discovering the key genes related to the biosynthetic pathway and the biosynthesis of ginkgolides.
Ginkgo biloba/genetics* ; Ginkgolides ; Humans ; Lactones ; Plant Extracts ; Terpenes

OBJECTIVETo investigate the effects of Egb761, an extract of ginkgo biloba , and dipyridamole on inducible NO synthase (iNOS) in rabbits after myocardial ischemia-reperfusion injury.

METHODSAfter being established into ischemia-reperfusion injury model, 35 rabbits were divided randomly into 5 groups: Group A (the sham group), Group B (the model group), Group C (treated with dipyridamole 0.8 mg/kg), Group D (treated with Egb761, 40 mg/kg), and Group E (treated with Egb761 40 mg/kg combined with dipyridamole 0.8 mg/kg), all the medications were administered by intravenous injection 30 min after reperfusion. After administration, myocardial iNOS mRNA expression was detected by RT-PCR and western blot.

RESULTSMyocardial iNOS mRNA transcriptive expression in the 5 groups were A 0, B 157.11 +/- 17.73, C 202.6 +/- 21.84, D 356.13 +/- 24.18 and E 562.34 +/- 35.19 respectively, showing significant difference between the treated groups and group B (P <0.01). The translative expression of myocardial iNOS in the 5 groups were A 34.24 +/- 15.78, B 75.70 +/- 13.71, C 116.89 +/- 22.57, D 143.75 +/- 16.05 and E 195.09 +/- 22.25 respectively, showing significant difference between the treated groups and group B as well (P < 0.05, P < 0.01).

CONCLUSIONBoth Egb761 and dipyridamole could increase myocardial iNOS expression in transcriptive and translative levels in rabbits after myocardial ischemia-reperfusion injury, and the combined treatment of them shows a more significant effect.

Animals ; Dipyridamole ; therapeutic use ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Ginkgo biloba ; Male ; Myocardial Reperfusion Injury ; drug therapy ; enzymology ; genetics ; Myocardium ; enzymology ; Nitric Oxide Synthase Type II ; biosynthesis ; genetics ; Phytotherapy ; RNA, Messenger ; biosynthesis ; genetics ; Rabbits ; Random Allocation ; Transcription, Genetic

OBJECTIVETo investigate the intervention effect and mechanism of compound Ginkgo biloba (CGB) preparations on nonalcoholic fatty liver disease (NAFLD).

METHODThe C57BL/6 mouse NAFLD model was induced with high fat diets. Since the 2nd week after modeling, the mice were orally administered with 600 and 200 mg x kg(-1) x d(-1) CGB for eight weeks. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), cholesterol (CHOL) and LPS in serum, as well as pathological changes and expression of tumor necrosis factor-alpha (TNF-alpha) in hepatic tissues were observed. Changes in intestinal tight junction proteins ZO-1, Occludin, Claudin-1 in intestinal tissues were determined under microscopy.

RESULTCompared with the normal group, the model group showed obvious fatty degeneration in rat livers, with notable increase in TNF-alpha expression (P < 0.01), significant increases in ALT, AST, TG, CHOL and LPS in serum (P < 0.01, P < 0.05), injury in intestinal tight junction proteins, and remarkable declines in ZO-1, Occludin and Claudin-1 (P < 0.01). Compared with the model group, CGB high and low dose groups showed obvious relieves in fatty degeneration in rat livers and injury in intestinal tight junction proteins, significant reductions in TNF-alpha expression (P < 0.01, P < 0.05) and AST, TG, CHOL and LPS in serum (P < 0.01, P < 0.05) and remarkable increases in ZO-1 and Occludin expressions (P < 0.05).

CONCLUSIONCGB can protect intestinal tight junction proteins, reduce intestinal leakage, relieve fatty degeneration and inflammations in livers and prevent NAFLD occurrence and development.

Alanine Transaminase ; genetics ; metabolism ; Animals ; Aspartate Aminotransferases ; genetics ; metabolism ; Cholesterol ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; Fatty Liver ; drug therapy ; enzymology ; genetics ; metabolism ; Ginkgo biloba ; chemistry ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Triglycerides ; metabolism

OBJECTIVETo investigate the expression of tissue transglutaminase( tTG) in unilateral ureteral obstruction (UUO) rats and the intervention of Folium Ginkgo (GBE).

METHODThe animal models of unilateral ureteral obstruction (UUO) were used. Wistar rats were randomly divided into four groups, the Sham-operated group, the UUO group, the benazepril (Bena)-treated UUO group and the GBE-treated group. The rats were sacrificed at day 14. Histological changes in renal tubular interstitium were observed with HE and Masson staining, and the mRNA and protein levels of tTG and FN were detected by RT-PCR and immunohistochemistry.

RESULTCompared with the sham group, the expression of tTG and FN were significantly increased (P < 0.01), and decreased after been treated by Bena and GBE (P < 0.05).

CONCLUSIONBena and GBE may suppress the development of fibrosis partially via down-regulation of tTG expression.

Animals ; Drugs, Chinese Herbal ; pharmacology ; Fibrosis ; Gene Expression Regulation, Enzymologic ; drug effects ; Ginkgo biloba ; chemistry ; Immunohistochemistry ; Kidney ; drug effects ; enzymology ; metabolism ; pathology ; Male ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Wistar ; Transglutaminases ; genetics ; metabolism

OBJECTIVETo evaluate the effects of Ginkgo biloba extract (EGB) on CCl(4)-induced liver fibrosis and to investigate the underlying mechanisms.

METHODSRats were divided into the following groups: normal control group, CCl(4) model group, low dose EGB group, moderate dose EGB group and high dose EGB group. The rat liver fibrosis model was induced by intraperitoneal injection of CCl(4) twice a week for 8 weeks. The model rats of the three EGB treated groups were given 0.25 g/kg, 0.5 g/kg, 1.0 g/kg of EGB by stomach tubes every day. At the end of the eighth week, the blood and liver specimens were obtained. The expressions of nuclear factor kappaB (NF-kappaB) P65, and alpha-smooth muscle actin (alpha-SMA) were detected by immunohistochemistry. Radioimmunoassay was exploited to evaluate serum hyaluronic acid (HA) and laminin (LN) levels. Electrophoretic mobility shift assay (EMSA) was used to confirm the nuclear translocation activity of NF-kappaB in liver tissues. The mRNA expression of transforming growth factor-beta1 (TGFbeta1) and collagen I was determined by RT-PCR. Malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in liver tissues and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the sera were also examined.

RESULTSCCl(4) administration induced liver fibrosis, which was inhibited by EGB in a dose-dependent manner. The histopathologic scores of liver fibrosis, the levels of serum ALT, AST, HA and LN were significantly lower in the rats treated with EGB compared with those not treated (P <0.01 or P <0.05). SOD and GSH-Px activities were notably elevated and MDA content was significantly lower in the rats treated with EGB (P <0.01 or P <0.05), indicating reduced oxidative stress. Immunohistochemical staining demonstrated inhibition of hepatic stellate cell (HSC) activation (in terms of alpha-SMA expression) and NF-kappaB P65 expression in the livers of the EGB-treated rats. As determined by EMSA and RT-PCR, activation of NF-kappaB, the mRNA expression of TGFbeta1 and collagen I were significantly higher in model group rats, but obviously lower in EGB treated rats.

CONCLUSIONEGB is able to ameliorate liver injury and prevent rats from CCl(4)-induced liver fibrosis by suppressing oxidative stress. This process may be related to inhibiting the expression of TGFbeta1 and the induction of NF-kappaB on HSC activation.

Animals ; Carbon Tetrachloride ; Carbon Tetrachloride Poisoning ; Drugs, Chinese Herbal ; therapeutic use ; Ginkgo biloba ; Liver Cirrhosis, Experimental ; chemically induced ; drug therapy ; Male ; NF-kappa B ; biosynthesis ; genetics ; Phytotherapy ; Plant Leaves ; Rats ; Rats, Wistar ; Transforming Growth Factor beta ; biosynthesis ; genetics

AIMTo study the expression of vascular endothelial growth factor (VEGF) in U937 foam cells and the inhibitory effect of salvianolic acid B and Ginkgo biloba extract in vitro.

METHODSU937 cells were incubated with 80 mg.L-1 oxidized low density lipoprotein (OX-LDL) for 48 h and a macrophage-derived foam cell model was established. The VEGF concentration in the media was determined by ELISA; the VEGF protein expression in cells was measured with immunohistochemistry; the VEGF mRNA level in cells was measured by in situ hybridization; the positive ratio detected by a morphometrical analysis system was used as the amount of the VEGF protein expression and the mRNA level.

RESULTSAfter U937 cells were incubated with OX-LDL, VEGF expression level increased greatly both in the cells and in the media. Salvianolic acid B and Ginkgo biloba extract were shown to remarkably inhibit the increase of VEGF. After treated with 10 micrograms/L-1 salvianolic acid B and Ginkgo biloba extract, the VEGF protein concentration in the media and positive ratio in the cells decreased compared with foam cells. After treated with 10 micrograms.L-1 salvianolic acid B and 100 micrograms.L-1 Ginkgo biloba extract, the VEGF mRNA level decreased measured by in situ hybridization.

CONCLUSIONA high VEGF expression level was determined in U937 foam cells. Salvianolic acid B and Ginkgo biloba extract were found to inhibit VEGF expression significantly in U937 foam cells in vitro.

Benzofurans ; pharmacology ; Foam Cells ; drug effects ; metabolism ; Gene Expression ; drug effects ; Ginkgo biloba ; chemistry ; Humans ; Plant Extracts ; isolation & purification ; pharmacology ; RNA, Messenger ; biosynthesis ; genetics ; U937 Cells ; Vascular Endothelial Growth Factor A ; biosynthesis ; genetics

In this study, the synergistic effect of 6-[4-(1-cyclohexyl-1H-tetrazol-5-yl) butoxy]-3,4-dihydro-2(1H)-quinolinone (cilostazol) and Ginkgo biloba extract (GbE) was examined in apolipoprotein E (ApoE) null mice. Co-treatment with GbE and cilostazol synergistically decreased reactive oxygen species (ROS) production in ApoE null mice fed a high-fat diet. Co-treatment resulted in a significantly decreased atherosclerotic lesion area compared to untreated ApoE mice. The inflammatory cytokines and adhesion molecules such as monocyte chemoattractant-1 (MCP-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and VCAM-1 which can initiate atherosclerosis were significantly reduced by the co-treatment of cilostazol with GbE. Further, the infiltration of macrophages into the intima was decreased by co-treatment. These results suggest that co-treatment of GbE with cilostazol has a more potent anti-atherosclerotic effect than treatment with cilostazol alone in hyperlipidemic ApoE null mice and could be a valuable therapeutic strategy for the treatment of atherosclerosis.
Animals ; Apolipoproteins E/genetics/physiology ; Atherosclerosis/*drug therapy ; Cytokines/metabolism ; Disease Models, Animal ; Drug Synergism ; Ginkgo biloba/*chemistry ; Humans ; Macrophages/cytology/drug effects ; Male ; Mice ; Mice, Nude ; Plant Extracts/*administration & dosage/chemistry ; Reactive Oxygen Species/*metabolism ; Tetrazoles/*administration & dosage

BACKGROUNDThe extract of Ginkgo biloba leaves tablets, ginaton, is widely used in treating ischemic cerebrovascular disease in the clinic. This study aimed to investigate the expression of aquaporin-1 (AQP-1) in rat lung with ischemia/reperfusion injury after pretreatment with ginaton, and whether the pretreatment with ginaton reduces the acute lung injury caused by ischemia/reperfusion injury.

METHODSAdult Wistar rats were divided into two groups. Some rats were used as donors (n = 20), the others as recipients (n = 20). Left lungs of donor rats were used for the isolated lung reperfusion model, which perfused only with low potassium dextran (LPD) solution as group A (n = 10); the others were pretreated with ginaton before reperfusion as group C (n = 10). Right lung of donor rat without any treatment was used as a control group (group B and group D, n = 10 for each group). After the model was established, the expression of AQP-1 in the lung tissues was examined by immunohistochemistry, Western blotting, and reverse transcriptase-polymerase chain reaction.

RESULTSImmunohistochemical examination revealed that AQP-1 was expressed in endothelia. Immunoblotting demonstrated that the relative gray values of AQP-1 protein in groups A and C were 0.65±0.06, 0.88±0.11, respectively. The relative gray values of the mRNA expression in groups A and C were 0.30±0.08, 0.49±0.11, respectively. The expression of AQP-1 protein and mRNA in group C was significantly higher than in group A (P < 0. 05).

CONCLUSIONThe pretreatment with ginaton can reduce the acute lung injury caused by ischemia/reperfusion.

Animals ; Aquaporin 1 ; genetics ; metabolism ; Ginkgo biloba ; chemistry ; Immunohistochemistry ; Lung ; drug effects ; metabolism ; Plant Extracts ; therapeutic use ; Plant Leaves ; chemistry ; Rats ; Rats, Wistar ; Reperfusion Injury ; drug therapy ; metabolism ; Tablets

OBJECTIVETo explore the protective effects of extract of Ginkgo biloba (EGB) in adriamycin (ADR)-induced heart failure (HF) and the mechanism of ghrelin peptide.

METHODWistar rats were randomly divided into three groups: control group, HF group and EGB group. ADR was injected in the rats of HF group and EGB group by caudal vein. After the last injection, the rats in EGB group were given intra-gastric administration of EGB solution (100 mg x kg(-1) x d(-1)). Three weeks later, cardiac function was detected; Ghrelin levels in plasma and myocardium were measured by radio-immunology assay (RIA); High energy phosphates (HEP) contents in myocardium were measured by HPLC; Myocardial gene expression of ghrelin was measured by RT-PCR.

RESULTCompared with control group, HF group had obviously decreased index of cardiac function, and these indexes such as +/- dp/dt max in EGB group were higher than those in ADR group. Plasma ghrelin level in HF group was higher than that in control group while myocardial ghrelin level was significantly lower than that in control group. Myocardial ATP content and gene expression of ghrelin mRNA in HF group were significantly lower than those in control group; Plasma ghrelin level in EGB group was significantly increased. Myocardial ATP content and gene expression of ghrelin mRNA in EGB group were significantly higher than those in HF group, and were closed to those of control group.

CONCLUSIONMyocardial energy dysfunction is an important reason of ADR-induced HF. EGB therapy can improve cardiac function and energy metabolism in HF rats, partly because it might increase the expression and production of ghrelin, which can promote positive energy metabolism.

Animals ; Disease Models, Animal ; Doxorubicin ; adverse effects ; Gene Expression ; drug effects ; Ghrelin ; metabolism ; Ginkgo biloba ; chemistry ; Heart Failure ; drug therapy ; genetics ; metabolism ; Humans ; Male ; Myocardium ; metabolism ; Plant Extracts ; administration & dosage ; Protective Agents ; administration & dosage ; Random Allocation ; Rats ; Rats, Wistar

This study is to investigate the protein and mRNA expressions of pro-inflammatory and anti-inflammatory cytokines in U937 foam cells and effects of Ginkgo biloba extract (GbE) on the cytokines. U937 cells were cultured with different concentrations of GbE (0.1, 1, and 10 microg x L(-1)), and stimulated by 100 mg x L(-1) oxidized low density lipoprotein (ox-LDL) for 24 h. The expressions of interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) in culture solution were detected by enzyme-linked immunosorbant assay (ELISA) and reverse transcriptase polymerase chain reaction (RT-PCR). The results showed that incubated with 100 mg x L(-1) ox-LDL for 24 h, the U937 cells became foam cells, the protein or mRNA expressions of IL-1beta, TNF-alpha, IL-10, and its receptor IL-10R in U937 foam cells were higher markedly than those in normal U937 cells. When the cells were pretreated with GbE (0.1, 1, and 10 microg x L(-1)), the increases of IL-1beta and TNF-alpha in U937 foam cells were remarkably inhibited, but IL-10 expression increased greatly. Especially when cells were pretreated with 10 microg x L(-1) GbE, the protein and mRNA expressions of IL-1beta and TNF-alpha were markedly lower than those in U937 foam cells. The protein expression of IL-10 and mRNA expressions of IL-10 and its receptor IL-10R were markedly higher than those in U937 foam cells. GbE inhibited production of pro-inflammatory cytokines IL-1beta and TNF-alpha, but up-regulated the production of anti-inflammatory cytokine IL-10 and its receptor IL-10R in U937 foam cells, which might be related with its anti-atherosclerotic actions.
Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Foam Cells ; metabolism ; Ginkgo biloba ; chemistry ; Humans ; Interleukin-10 ; biosynthesis ; genetics ; Interleukin-1beta ; biosynthesis ; genetics ; Lipoproteins, LDL ; Plants, Medicinal ; chemistry ; RNA, Messenger ; metabolism ; Receptors, Interleukin-10 ; biosynthesis ; genetics ; Tumor Necrosis Factor-alpha ; biosynthesis ; genetics ; U937 Cells