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 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

In the present study, we analyzed the role of Ginkgo biloba extract in lipopolysaccharide(LPS)-induced acute lung injury (ALI). ALI was induced in mice by intratracheal instillation of LPS. G. biloba extract (12 and 24 mg·kg(-1)) and dexamethasone (2 mg·kg(-1)), as a positive control, were given by i.p. injection. The cells in the bronchoalveolar lavage fluid (BALF) were counted. The degree of animal lung edema was evaluated by measuring the wet/dry weight ratio. The superoxidase dismutase (SOD) and myeloperoxidase (MPO) activities were assayed by SOD and MPO kits, respectively. The levels of inflammatory mediators, tumor necrosis factor-a, interleukin-1b, and interleukin-6, were assayed by enzyme-linked immunosorbent assay. Pathological changes of lung tissues were observed by H&E staining. The levels of NF-κB p65 and COX-2 expression were detected by Western blotting. Compared to the LPS group, the treatment with the G. biloba extract at 12 and 24 mg·kg(-1) markedly attenuated the inflammatory cell numbers in the BALF, decreased NF-κB p65 and COX-2 expression, and improved SOD activity, and inhibited MPO activity. The histological changes of the lungs were also significantly improved. The results indicated that G. biloba extract has a protective effect on LPS-induced acute lung injury in mice. The protective mechanism of G. biloba extract may be partly attributed to the inhibition of NF-κB p65 and COX-2 activation.
Acute Lung Injury ; chemically induced ; drug therapy ; metabolism ; Animals ; Bronchoalveolar Lavage Fluid ; cytology ; Cell Count ; Cyclooxygenase 2 ; genetics ; metabolism ; Enzyme-Linked Immunosorbent Assay ; Gene Expression ; drug effects ; Ginkgo biloba ; chemistry ; Interleukin-1beta ; analysis ; Interleukin-6 ; analysis ; Lipopolysaccharides ; Lung ; immunology ; pathology ; Male ; Mice ; Mice, Inbred BALB C ; Peroxidase ; metabolism ; Phytotherapy ; Plant Extracts ; pharmacology ; Pulmonary Edema ; Superoxide Dismutase ; metabolism ; Transcription Factor RelA ; genetics ; metabolism ; Tumor Necrosis Factor-alpha ; analysis

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

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

OBJECTIVETo observe the effect of Ginkgo biloba extract (GbE) against the bleomycin induced pulmonary fibrosis and to investigate its mechanisms.

METHODSD rats were randomly divided into 3 groups: Control group, BLM + NS group and BLM + GbE group (n = 6 in each time point of each group). Rats in each group were sacrificed on the 14th and 30th day after endotracheal injection of bleomycin A5. Lung injury through HE stain and pulmonary fibrosis through Masson stain were observed by light microscope. The content of collagen protein in lung tissue and malondialdehyde (MDA) in plasma were assayed by biochemical methods. The expressions of TGF-beta1 in tissue and bronchoalveolar lavage fluid (BALF) were detected by immunohistochemistry and immunocytochemistry respectively.

RESULTCompared with control group, every datum in each time point in BLM + NS group showed significant changes which indicated the success of the model. Compared with BLM + NS (14 d) group, MDA in serum and TGF-beta1 in alveolar macrophage were significantly reduced in BLM + GbE (14 d) group. The data in BLM + GbE (30 d) group were compared with those in BLM + NS (30 d) group as follows. The lung injury and fibrosis were significantly ameliorated, the content of collagen in lung tissue and MDA in plasma were significantly reduced, the expression of TGF-beta1 in lung tissue was significantly reduced, however the expression of TGF-beta1 in BALF cells was not significantly changed.

CONCLUSIONGbE inhibited bleomycin induced lung injury and fibrosis in rats. The possible mechanisms were that GbE could inhibit the expression of TGF-beta1 in alveolar macrophage in early stage of fibrosis (14 d) and in noninflammatory cells in proliferative stage (30 d), and GbE could also attenuate the oxidative stress induced by bleomycin.

Animals ; Bleomycin ; adverse effects ; analogs & derivatives ; Bronchoalveolar Lavage Fluid ; chemistry ; Disease Models, Animal ; Drugs, Chinese Herbal ; administration & dosage ; Ginkgo biloba ; chemistry ; Humans ; Macrophages, Alveolar ; drug effects ; metabolism ; Male ; Malondialdehyde ; metabolism ; Pulmonary Fibrosis ; chemically induced ; drug therapy ; genetics ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Transforming Growth Factor beta1 ; genetics ; metabolism

OBJECTIVETo investigate the changes in contents of cycloxygenase-2 (COX-2) and its downstream effectors in rat's myocardial ischemia/reperfusion (I/R) model and observe the effects of precondition with GBE50 (Ginkgo biloba extract 50) and Salviae miltiorrhizae (SM) on them.

METHODSRat's I/R model was established by 30-min left anterior descending coronary artery occlusion followed with 60-min reperfusion. Animals were divided into the model control group, the sham-operated group and the tested groups (received 1-week precondition with GBE50 and SM respectively via intragastric infusion before modeling). COX-2 mRNA expression in myocardium was detected by real-time PCR; contents of thromboxane B2 (TXB2) and 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha) were measured by radioimmunoassay.

RESULTSThe mRNA expression of COX-2 in the model group was obviously higher than that in the sham-operated group (P < 0.001), while that in the tested groups was down-regulated significantly (P < 0.01), and the content of TXB2 as well as the ratio of TXB2/PGF1alpha was reduced significantly (P < 0.05). Besides, SM also showed the up-regulation effect on 6-keto-PGF1alpha content in myocardium (P < 0.05).

CONCLUSIONCOX-2 affects the myocardium through thromboxane A2 and prostacyclin after I/R; both GBE50 and SM can inhibit the production of COX-2, but they may act in different paths.

6-Ketoprostaglandin F1 alpha ; metabolism ; Animals ; Cyclooxygenase 2 ; genetics ; metabolism ; Drugs, Chinese Herbal ; therapeutic use ; Ginkgo biloba ; chemistry ; Ischemic Preconditioning, Myocardial ; methods ; Male ; Myocardial Ischemia ; physiopathology ; Myocardial Reperfusion Injury ; metabolism ; pathology ; Myocardium ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Salvia miltiorrhiza ; chemistry ; Thromboxane B2 ; metabolism

OBJECTIVETo study the effect of the Chinese compound prescription Ginkgo biloba Pingchan Recipe (GBPR) on experimental Parkinson disease (PD) in mice and explore the possible mechanism.

METHODSMale C57/BL6J mice were divided into normal control, PD model and treatment groups. PD model was established by intraperitoneal injection with 1-methl-4-phenyl-1,2,3,6-tetrahydropyridin (MPTP) in the mice, and in the treatment group, GBPR was administered intragastrically after the injection. The mice were sacrificed 14 and 28 days later, and using in situ hybridization with Digoxin-labeled nNOS cDNA oligonucleotide probe, neuronal nitric oxide synthase (nNOS) mRNA was detected in the striatum and substantia nigra in the brain of mice.

RESULTSnNOS mRNA expression was detected in the striatum and substantia nigra of the PD model mice, and GBPR treatment significantly reduced its expressions.

CONCLUSIONGBPR has obvious inhibitory effect against the neurotoxicity of NO probably by producing an anti-oxiditive effect through decreasing nNOS synthesis in the brain.

Animals ; Brain ; drug effects ; enzymology ; metabolism ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Gene Expression Regulation, Enzymologic ; drug effects ; Ginkgo biloba ; chemistry ; Male ; Mice ; Mice, Inbred C57BL ; Neostriatum ; drug effects ; metabolism ; Nitric Oxide Synthase Type I ; genetics ; Parkinson Disease ; enzymology ; genetics ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Substantia Nigra ; drug effects ; 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 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