Mechanism Of Ginkgo Biloba Extract Research Articles

WITHDRAWN: Experimental study on improvement of lung injury in septic rats by inhibiting RIOK3-ferritin autophagy axis with Ginkgo biloba extract

IntroductionThis study aimed to explore the mechanism of Ginkgo biloba extract(GBE, 银杏叶提取物) improving lung injury in septic rats by interfering with ferritin autophagy. MethodsA rat model of sepsis was established by cecal puncture method, and the animals were randomly divided into 6 groups, including control group, sham operation group, model group and GBE low, medium and high concentration treatment groups. Groups GBE low, medium and high concentration were given intraperitoneal injection of low dose (10mg/kg), medium dose (20mg/kg) and high dose (40mg/kg) GBE, respectively. Detect relevant indicators. ResultsIt was found that the lung tissue of rats in the model group had obvious pathological damage, and the expression of ferritin (FTH1) was significantly reduced, the expression of ferritin autophagy-related factors such as RIOK3, NCOA4, and LC3B was significantly increased, and the contents of Fe2+, malondialdehyde (MDA), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and the lung/body weight ratios were significantly increased. GBE significantly improved the pathological damage of lung tissue in rats, increased the expression of FTH1, knocked down the expression of RIOK3, NCOA4 and LC3B, reduced the contents of Fe2+, MDA, IL-6, and TNF-α, and the lung/body weight ratios, especially in the medium-dose GBE group. ConclusionsGBE can down-regulate the expression of NCOA4 by inhibiting the expression of RIOK3, thereby inhibiting ferritin autophagy and ferroptosis, and ameliorating acute lung injury in sepsis rats. The best effect is found in medium concentration GBE (20mg/kg).

Evaluating the Effectiveness of Ginkgo Biloba Extract in Alleviating Dizziness and Improving Nutritional Status in Cerebral Arteriosclerosis Patients

In this study, we aimed to evaluate the therapeutic efficacy of Ginkgo biloba extract in ameliorating dizziness symptoms and enhancing nutritional status in patients diagnosed with cerebral arteriosclerosis. A total of 170 patients suffering from cerebral arteriosclerosis were selected and divided randomly into two groups: a control group receiving conventional treatment and an experimental group receiving standard treatment plus Ginkgo biloba extract. A comparative analysis revealed that the experimental group demonstrated significant improvement in neurological function and mobility post-treatment, exhibited reduced dizziness symptoms and improved hemodynamics in the vertebral and basilar arteries compared with the control group (P < 0.05). The experimental group exhibited a significantly better nutritional status post-treatment compared with the control group (P < 0.05). To further elucidate the underlying mechanisms of Ginkgo biloba extract’s effects on cerebral arteriosclerosis, a cerebral arteriosclerosis rat model was developed. The results indicated that Ginkgo biloba extract intervention mitigated inflammation and oxidative stress in the brain tissues of rats with cerebral arteriosclerosis, leading to reduced pathological damage. These findings suggest that Ginkgo biloba extract has the potential to relieve cerebral arteriosclerosis-related dizziness and improve nutritional status in patients, offering a promising novel therapeutic modality for the clinical management of cerebral arteriosclerosis.

The Mechanism of Ginkgo Biloba Extract in Treating Glioma

<i>Objective: </i>To explore the active components of ginkgo biloba and the possible targets and pathways for treating glioma. <i>Methods</i>: The chemical components and corresponding targets of Ginkgo biloba were searched by TCMSP, and the "component-target" network map was constructed by Cytoscape. The GenCards database, OMIM database and Disgenet database were used to search for glioma-related genes. Ginkgo biloba targets and glioma gene intersections were extracted using R software, and Veen maps were drawn to obtain key targets. PPI network construction and GO and KEGG enrichment analysis were performed by key targets. <i>Results: </i>A total of 27 active ingredients in Ginkgo biloba leaves and 5770 glioma target genes were collected, and 48 key targets were obtained. PPI analysis showed that the core targets were IL6, ESR1, EGFR, PPARG, VEGFA, CYP3A4, AHR, AR, PGR, etc. GO enrichment analysis is mainly concentrated in nuclear receptor activity, neurotransmitter receptor activity, fatty acid metabolic processes, response to foreign stimuli, etc. KEGG enrichment pathways are mainly manifested in: cholinergic synapses, resistance to EGFR tyrosine kinase inhibitors, tumor necrosis factor signaling pathway PI3K-Akt signaling pathway, etc. <i>Conclusion</i>: Ginkgo biloba can treat glioma through multi-target and multi-pathway, which is in line with the characteristics of holistic treatment of diseases in traditional Chinese medicine.

Inflammatory mechanisms of Ginkgo Biloba extract in improving memory functions through lncRNA-COX2/NF-κB pathway in mice with status epilepticus.

This study was to explore whether Ginkgo biloba extract (GBE) improve memory impairment by alleviating neuroinflammation signaling in mice with status epilepticus. The status epilepticus (SE) mice model was established by pilocarpine and treated with 100 mg / kg of GBE for 14 days. Spontaneous alternation of Y-maze and new object recognition were used to explore memory impairment. To examine glial cell activation, we performed immunohistochemistry and immunofluorescence staining. The activation of NF-κB signaling and the expression level of lncRNA-COX2 were detected by Western blot and qRT-PCR, respectively. Adeno-associated virus lncRNA-COX2 was injected into mice for overexpression of lncRNA-COX2. After GBE treatment, the spontaneous alternation rate and the recognition coefficient in SE mice were both increased. Moreover, activation of glial cells, NF-κB signaling and lncRNA-COX2 were significantly decreased in SE mice. In the GBE-treated SE mice with lncRNA-COX2 overexpression, NF-κB signaling was up-regulated again; the reduced level of inflammation factors was reversed; the GBE-rescued spontaneous alternation rate of Y-maze was eliminated. Our results suggested that GBE reduces the hippocampal inflammation by down-regulating lncRNA-COX2 / NF-κB signaling in the SE mice, leading to the decrease of neuronal damage and the improvement of memory functions.

Hepatoprotective effect of Ginkgo biloba extract against methotrexate-induced hepatotoxicity via targeting STAT3/miRNA-21 axis

The usage of the chemotherapeutic agent methotrexate (MTX) was associated with hepatotoxicity that minimized its clinical use. The Ginkgo biloba extract (GBE) was used before to alleviate the MTX-induced liver injury through its antioxidant activity. This work was carried out to elucidate other molecular hepatoprotective mechanisms of GBE via examining the IL-6/STAT3 pathway in addition to the miRNA-21 expression in hepatic tissue. Sprague Dawley rats were allocated into four groups: normal control (NC); Ginkgo biloba extract control (GBEC); methotrexate (MTX); and Ginkgo biloba extract and methotrexate (GBE + MTX) group. GBE was administered orally 60 mg/kg/day for 10 days while MTX was intraperitoneally injected with 20 mg/kg on day 5. After the experiment, the serum was separated for liver enzyme determination while liver tissues were collected for biochemical and histopathological examinations. MTX induced marked elevation in the liver enzymes, hepatic IL-6, and HGF mRNA expressions, phospho-STAT3/STAT3 ratio, and miRNA-21 hepatic expression when compared with the NC group. Liver injury was observed histopathologically after MTX. The GBE administration reversed these biochemical alterations and improved liver histopathology. The hepatoprotective mechanism of GBE against MTX-induced hepatotoxicity via the modulation of the IL-6/STAT3 signaling pathway and the downregulation of the miRNA-21 hepatic expression was reported for the first time.

Effects of GBE50 on LPS/ATP induced NLRP3 inflammasome activation in primary rat microglia

In this study, the anti-inflammatory mechanism of Ginkgo biloba extract 50 (GBE50) and its mechanism of action on NLRP3 inflammatory corpuscles were observed by primary microglia cells. LPS/ATP was used to stimulate microglia, and the best time for stimulation and optimal concentration of GBE50 were screened. Pro-inflammatory cytokine IL-1β and TNF-α was determined by ELISA. Western blot was performed to observe the protein expression of NLRP3, ASC, caspase-1 and IL-1β in cultured primary rat microglia. Effect of GBE50 on NLRP3 inflammatory corpuscle aggregation was detected by CO-IP. GBE50 (10 mg·L⁻¹) preconditioning could significantly inhibit the expression of LPS (100 μg·L⁻¹,12 h), ATP (5 mmol·L⁻¹, 30 min) induced primary microglia corpuscle associated protein, inflammatory corpuscle aggregation, and the release of inflammatory factors IL-6 and TNF-α. These results indicated that GBE50 could inhibit the secretion of inflammatory factors after microglia activation, which is related to down regulating the protein expression and activity of NLRP3 inflammatory corpuscle.

Anti-neuroinflammatory effects of Ginkgo biloba extract EGb761 in LPS-activated primary microglial cells

BackgroundNeuroinflammation is a key factor of Alzheimer's disease (AD) and other neurodegenerative conditions. Microglia are the resident mononuclear immune cells of the central nervous system (CNS). They play an essential role in the maintenance of homeostasis and responses to neuroinflammation. Ginkgo biloba extract EGb 761 is one of the most commonly used natural medicines owing to its established efficacy and remarkable biological activities especially in respect to CNS diseases. However, only few studies have addressed the effects and mechanisms of Ginkgo biloba extract in microglia activation. MethodsWe measured the production of pro-inflammatory mediators and cytokines by ELISA and analyzed gene expressions by qRT-PCR and Western Blot in LPS treated cultured primary rat microglia. ResultsThe Ginkgo biloba extract EGb 761 significantly inhibited the release of prostaglandin E2 (PGE2) and differentially regulated the levels of pro-inflammatory cytokines. The inhibition of LPS-induced PGE2 release in primary microglia was partially dependent on reduced protein synthesis of mPGES-1 and the reduction in the activation of cytosolic phospholipase A2 (cPLA2) without altering COX-2 enzymatic activity, inhibitor of kappa B alpha (IkappaBalpha) degradation, and the activation of multiple mitogen activated protein kinases (MAPKs). Altogether, we showed that EGb 761 reduces neuro-inflammatory activation in primary microglial cells by targeting PGE2 release and cytokines. ConclusionGinkgo biloba extract EGb 761 displayed anti-neuroinflammatory activity in LPS-activated primary microglia cells. EGb 761 was able to reduce neuroinflammatory activation by targeting the COX/PGE2 pathway. This effect might contribute to the established clinical cognitive efficacy in Alzheimer's disease, vascular and mixed dementia.

NIK‑ and IKKβ‑binding protein contributes to gastric cancer chemoresistance by promoting epithelial‑mesenchymal transition through the NF‑κB signaling pathway.

Systematic chemotherapy is indispensable for gastric cancer patients with advanced stage disease, but the occurrence of chemoresistance drastically limits treatment effectiveness. There is a tremendous need for identifying the underlying mechanism of chemoresistance. NIK‑ and IKKβ‑binding protein (NIBP) (also known as TRAPPC9, trafficking protein particle complex9) is a regulator of the cytokine‑induced NF‑κB signaling pathway which has been proven to play pivotal roles in the progression of various malignancies. Nevertheless, it is still ambiguous whether NIBP is involved in the chemoresistance of gastric cancer. The aim of the present study was to investigate the effect of NIBP on chemotherapy resistance of gastric cancer (GC) and to research the mechanisms of Ginkgo biloba extract761 (EGb761®) on reversing chemoresistence which has been confirmed in our previous study. In the present study, the results of immumohistochemisty revealed that the positive staining rates of NIBP, NF‑κB p65 and NF‑κB p‑p65 in gastric cancer tissues were obviously higher than those in normal tissues. Furthermore, a close correlation was found to exist between the expression of NIBP and NF‑κB p65 (p‑p65) in gastric cancer tissues. Moreover, the overexpression of NIBP was closely related to tumor differentiation, depth of invasion, clinical stage and lymphatic metastasis in gastric cancer. Western blot analysis, real‑time PCR, MTT assay and flow cytometric analysis were performed and the results demonstrated that compared with the gastric cancer SGC‑7901 cells, the expression of NIBP, NF‑κB p65, NF‑κB p‑p65 and mesenchymal marker vimentin were significantly increased in gastric cancer multidrug‑resistant SGC‑7901/CDDP cells, and the epithelial cell marker ZO‑1 was significantly decreased. Meanwhile, it was found that SGC‑7901/CDDP cells were accompanied by spindle‑like mesenchymal appearance and upregulation of stem cell marker CD133 which has been verified to be an upstream regulatory gene of epithelial‑mesenchymal transition (EMT). Further research confirmed that downregulation of NIBP by Ginkgo biloba extract (EGb) 761 EGb 761 suppressed the cis‑diamminedichloroplatinum(II) (CDDP)‑induced NF‑κB signaling pathway, EMT and the expression of CD133 in SGC‑7901 and SGC‑7901/CDDP cells. Altogether, these data indicate that the NIBP‑regulated NF‑κB signaling pathway plays a pivotal role in the chemoresistance of gastric cancer by promoting CD133‑induced EMT.

The Antibiofilm Effect of Ginkgo biloba Extract Against Salmonella and Listeria Isolates from Poultry.

Salmonella spp. and Listeria spp. are common foodborne pathogens in poultry and have caused a large number of outbreaks worldwide. Biofilm formation is common in the food industry and is also a mechanism of antimicrobial resistance. The aim of this work was to investigate the antimicrobial effect and mechanism of Ginkgo biloba extract against the biofilm formation of Salmonella and Listeria isolates from poultry at retail markets. Bacteria detection, isolation, and enumeration were carried out on 27 chicken and 29 ducks at retail markets. The effects of temperature and G. biloba extract against biofilm formation of Salmonella and Listeria isolates were measured using the crystal violet assay and swimming and swarming motilities. The monitoring results of Salmonella and Listeria in 56 poultry carcasses at retail markets in Korea showed that the prevalence of Salmonella spp. in poultry was low (5.4%), but the prevalence of Listeria spp (78.6%) was high. L. innocua was the predominant serotype (80%) in the isolated Listeria species. Temperature, strain, and surface affected the biofilm formation of Salmonella spp. and Listeria spp. L. innocua showed the best biofilm formation ability on a 96-well plate, while Salmonella Enteritidis formed the most biofilm on a glass slide. Biofilm formation abilities of Salmonella spp. and Listeria spp. were increased with the increase of temperature. G. biloba extract at 75 μg/mL significantly inhibited biofilm formation of Salmonella spp. and Listeria spp (p < 0.05). The mechanism of the antibiofilm effect of the G. biloba extract showed that the motility reduction may be one of the mechanisms of G. biloba extract against some serotypes of Salmonella and Listeria, but not L. monocytogenes. The findings of this study provided the basis for the application of G. biloba extract as a food additive to promote the quality and safety of poultry products.

Protection of Vascular Endothelial Cells Injured by Angiotensin II and Hypoxia In Vitro byGinkgo biloba(Ginaton)

The objective of this study was to explore the protective effect and the possible mechanism of Ginkgo biloba extract (Ginaton) on human vascular endothelial cells (VECs) injured by angiotensin II (Ang-II) and hypoxia. The human aortic VECs were divided into different groups to observe the changes in endothelin (ET), calcium concentration ([Ca(2+)]i), and mitochondrial membrane potential (MMP). The results showed that Ginaton had inhibited ET secretion induced by hypoxia and Ang-II (P < .01). the protection offered by Ginaton at mid (10 mg/mL) and low (5 mg/mL) concentrations was obviously better than that offered at high concentration (25 mg/mL). The [Ca(2+)]i increased and MMP decreased significantly in both hypoxia group and Ang-II group (P < .01); however, the changes in [Ca(2+)]i and MMP could be meliorated by Ginaton. This study suggested that Ginaton could effectively protect VECs against injury, and the dose used clinically would rather be low than too high for getting better results.

Effects of ginkgo biloba extract on the expression of inducible nitric oxide synthase and glial fibrillary acidic protein after local cerebral ischemia/reperfusion in rats

Objective To explore the protective effect and mechanism of ginkgo biloba extract on brain tissue after local cerebral ischemia and reperfusion in rats.Methods Eighty male Sprague-Dawley rats were randomly divided into two groups:control group (group A,normal saline injected,n =40),and ginkgo biloba extract intervention group (group B,ginkgo biloba extract injected,n =40),which were then subdivided into 4 subgrouops:post-reperfusion 1,3,6 and 24 h groups,10 in each sub-group.The model of right middle cerebral artery occlusion (MCAO) and reperfusion was made.Pathological changes in brain morphology were observed by hematoxylin and eosin (HE) staining.Immunohitochemistry was used to detect the inducible nitric oxide synthase (iNOS) changes.The expression of glial fibrillary acidic protein (GFAP) was examined by using enzyme linked immunosorbent assay (ELISA).Results (1) Necrosis,apoptosis and cytoplasmic vacuolatin of nerve cells were observed in group A,neuronal shape was difficult to be identified,and most of the cell structure disappeared.However,the injury was relieved at the same time points in group B as compared with that in group A; (2) Immunohitochemical results showed that there were a few iNOS expression positive cells 1 h after reperfusion,iNOS expression positive cells were obviously increased at 3 h after referfusion,and nucler translocation appeared.Analysis by Image-pro plus 5.0 showed that iNOS expression levels in group B (1851.38 ±242.12,2005.41 ± 290.52,2625.28 ±385.21,3142.5 ±425.72 respectively at 1,3,6 and 24 h) were significantly lower than those in group A (1950.25 ± 298.26,2232.45 ± 305.28,3251.22 ± 425.26,3965.36 ± 521.62 respectively at 1,3,6and 24 h) (P ＜ 0.05) ; (3) ELISA results showed that serum GFAP levels were increased after ischemiareperfusion,and those in group B [(275.29 ± 112.72),(308.72 ±124.11),(372.56 ± 185.62),(452.12 ± 145.26) ng/L respectively at 1,3,6 and 24 h] were significantly lower than those in group A [(437.17 ± 152.26),(490.27 ± 198.37),(583.45 ± 201.42),(656.26 ± 256.36) ng/L respectively at 1,3,6 and 24 h] (P ＜ 0.05).Conclusion iNOS and GFAP were significantly increased after the cerebral ischemia-reperfusion in rats.ginkgo biloba extract can significantly reduce the cerebral injury by down-regulating the expression of iNOS and GFAP,suggesting the protective effects of ginkgo biloba extract on the ischemic cerebral tissues. Key words: Ginkgo biloba extract; Ischemia/reperfusion injury; Apoptosis; Inducible nitric oxide synthase

Protective Effects of Ginaton on Vascular Endothelial Cells Injured by Angiotensin II and Hypoxia In Vitro

The objective of this study was to explore the protective effect and possible mechanism of Ginkgo biloba extract (Ginaton) on human vascular endothelial cells (VECs) injured by angiotensin II (Ang-II) and hypoxia. The human aortic VECs were divided into different groups to observe the changes in endothelin (ET), intracellular calcium concentration ([Ca(2+)]i), and mitochondrial membrane potential (MMP). The results showed that Ginaton had inhibited ET secretion induced by hypoxia and Ang-II (P < .01); the protective effects of mid (10 mg/mL) and low concentrations (5 mg/mL) of Ginaton was obviously higher than that of the high concentration (25 mg/mL); [Ca(2+)]i increased and MMP decreased significantly in both the hypoxia and the Ang-II groups (P < .01); however, the changes in [Ca(2+)]i and MMP could be meliorated by Ginaton. This study suggested that Ginaton could effectively protect VECs against injury, and lower dose would be used clinically rather than the higher dose for obtaining better results.

Effects of ginkgo biloba extract on the expression of inducible nitric oxide synthase and platelet-activating factor after local cerebral ischemia/reperfusion in rats

Objective To explore the protective effect and mechanism of ginkgo biloba extract (GBE) on brain tissue after local cerebral ischemia and reperfusion in rats.Methods Eight male SpragueDawley rats were randomly divided into two groups:control group ( group A,normal saline injected,n =40),GBE intervention group (group B,GBE injected,n =40),which were then divided into 4 subgrouops,namely,1 h,3 h,6 h and 24 h after reperfusion,10 in each sub-group.The model of right middle cerebral artery occlusion (MCAO) and reperfusion was made.Pathological changes in brain morphology were observed by Hematoxylin and Eosin (HE) staining; immunohitochemical method was used to detect the inducible nitric oxide synthase (iNOS) changes; platelet activating factor (PAF) was detected by enzyme linked immunosorbent assay (ELISA).Results Nerve cell necrosis,apoptosis and cytoplasmic vacuolatin were observed,neuronal shape was difficult to identify,and most of the cell structures disappeared in group A.The injury was relieved at the same time points in group B compared with that in group A.Immunohitochemical results showed that there were a few iNOS expression positive cells 1 h after reperfusion,which increased at 3 h after referfusion and had nucler translocation.Analysis by Image-pro plus 5.0 showed that iNOS expression levels in group B ( 1851.38 ±242.12,2005.41 ±290.52,2625.28 ±385.21,3142.50 ± 425.72) were significantly lower than those in group A ( 1950.25 ± 298.26,2232.45 ± 305.28,3251.22 ± 425.26,3965.36 ± 521.62) (P ＜ 0.05 ),respectively.ELISA results showed that serum PAF levels were increased after ischemia-reperfusion,peaked at 6 h,and decreased at 24 h.Serum PAF level were significantly lower in group B ( 15.36 ± 2.12,18.56 ± 3.28,28.21 ± 4.26,22.48 ± 4.21 ) μg/L than in group A (20.52 ± 4.26,28.25 ± 6.18,36.08 ± 7.45,30.26 ± 6.02) μg/L ( P ＜ 0.05).Conclusion iNOS,and PAF change significantly after the cerebral ischemia-reperfusion in rats,which may be involved in cerebral ischemia-reperfusion injury mechanism.GBE can significantly alleviate the cerebral injury by regulating the expression of iNOS and PAF,suggesting GBE can effectively protect the ischemic cerebral tissues. Key words: Ginkgo biloba extract; Cerebral ischemia; Reperfusion injury; Inducible nitric oxide synthase

The hepatic protective mechanism of Ginkgo biloba extract in rats with obstructive jaundice

The objective of our study was to examine the hepatic protective mechanism of Ginkgo biloba extract (GBE) in rats with obstructive jaundice (OJ). Twenty rats underwent bile duct ligation and received daily intraperitoneal injections of either control saline or Ginkgo biloba extract for 14 days. Ten sham-operated rats had their bile duct exposed but not ligated or sectioned. Serum alanine transaminase (ALT) was analyzed for liver function tests and liver damage was further assessed by histologic examination. The levels of endothelin 1 (ET-1) and nitric oxide (NO) in blood and liver homogenate were measured. The serum alanine transaminase was elevated in the bile duct ligation rats (BDL rats); GBE could significantly lower serum transaminase level and ameliorate liver histological damage. ET-1 and NO levels in both plasma and liver tissue were also elevated in common bile duct (CBD)-ligated rats, but this increase was significantly decreased by GBE treatment. Moreover, the degree of liver damage severity positively correlates with high levels of ET-1 and NO. GBE mediated the liver protective effect at least in part by suppressing overproduction of ET-1 and NO and restoring a proper balance between ET-1 and NO to some extent.

Ginkgo Biloba extract, via upregulation of heme oxygenase‐1, confers protection from oxidative stress‐related apoptosis induced by cigarette smoke extract in human lung endothelial cells

We investigated the cytoprotective effects and therapeutic mechanisms of Ginkgo Biloba extract (EGb) against apoptosis of human pulmonary artery endothelial cells (HPAECs) induced by cigarette smoke extract (CSE). Challenge of CSE (160 microgram/ml) caused reduction in cell viability, increases in reactive oxygen species (ROS) and promotion of caspase‐dependant apoptosis in HPAECs, all of which were alleviated by pretreatment with EGb (100 microgram/ml). Exposure of HPAECs to EGb alone produced activation of mitogen‐activated protein kinases (MAPKs), increase in nuclear level of transcription factor Nrf2 and upregulation of heme oxygenase‐1 (HO‐1, an oxidative stress‐responsive protein). This HO‐1 upregulation was eliminated by inhibitors of MAPKs. While gene knockdown by small interfering RNAs targeting HO‐1 prevented the EGb‐induced HO‐1 upregulation, it also abolished the antioxidant, anti‐apoptotic and cytoprotective effects of EGb in HPAECs challenged with CSE. We conclude that EGb confers protection from oxidative stress–related apoptosis induced by CSE in HPAECs and its antioxidant and anti‐apoptotic effects are mediated through upregulation of HO‐1. (Supported by NSC‐95‐2320‐B‐010‐025‐MY3).

Ginkgo biloba extract improves spatial memory in rats mainly but not exclusively via a histaminergic mechanism

In order to clarify the mechanism of Ginkgo biloba extract (GBE) on learning and memory, we studied the effect of GBE on spatial memory deficits induced by diphenhydramine, pyrilamine and scopolamine using the eight-arm radial maze performance of rats, in comparison with donepezil. Total error (TE), reference memory error (RME) and working memory error (WME) were used as indices of spatial memory deficits. Both GBE and donepezil caused a potent antagonistic effect on the increase in TE, RME and WME induced by diphenhydramine. GBE and donepezil also antagonized scopolamine-induced spatial memory deficits. Although the antagonistic effect of GBE on pyrilamine-induced spatial memory deficits was weak, a significant difference was observed with TE and WME. However, donepezil caused no antagonistic effect on pyrilamine-induced memory deficits. From these findings, we concluded that the effects of GBE are mainly contributable to cholinergic activity and perhaps partly due to a histaminergic mechanism.

Effects of Ginkgo biloba extract on cell proliferation, cytokines and extracellular matrix of hepatic stellate cells

Hepatic fibrosis is the common wound-healing response to chronic liver injury. Ginkgo biloba extract (GbE) has been indicated to reverse hepatic fibrosis and exhibit therapeutic effects both in vitro and in vivo. This study aimed to investigate the underlying mechanism of GbE using HSC-T6 cells, a subline of hepatic stellate cells (HSC) as a model. HSC-T6 cells were seeded into six-well plates and allowed to attach overnight. After exposure to different concentrations of GbE761 for 24 or 48 h, cell cycle analysis, semiquantitative RT-PCR, Western blotting analysis and analysis of ECM secretion were performed. It was revealed that GbE (1, 10, 100, 500 mg/l) suppressed HSC proliferation and caused G0/G1 phase arrest in a concentration-dependent manner. RT-PCR and Western blot assays were applied to detect the decline of transforming growth factor beta1(TGF-beta1) and connective tissue growth factor (CTGF) in both mRNA and protein levels after GbE treatment in HSC-T6 cells for 24 or 48 h. Meanwhile, GbE inhibited the synthesis of type I and type III collagens. Secretion of some extracellular matrix (ECM) proteins, such as type III procollagen (PC III), type IV collagen (collagen IV), laminin (LN), hyaluronic acid (HA), were all decreased in supernatant of GbE treated HSC cells. Our results suggest that GbE confers its anti-fibrosis effects through inhibiting HSC proliferation, reducing TGF-beta1 and CTGF expression and consequently suppressing the collagen production and ECM secretion.