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OBJECTIVE To investigate the inhibitory effects of Ginkgo biloba extract （GBE） on renal inflammation in diabetic nephropathy （DN） model mice， and its potential mechanism. METHODS KK/Ay mice were fed with high fat and high sugar to induce DN model. They were divided into model group， positive control group [metformin 200 mg/（kg·d）]， GBE low-dose and high-dose groups [100， 200 mg/（kg·d）]， with 6 mice in each group. Six C57BL/6J mice were fed with a regular diet as the control group. Administration groups were given relevant liquid intragastrically， control group and model group were given constant volume of normal saline intragastrically， once a day， for 8 consecutive weeks. The body weight， fasting blood glucose， 24-hour food intake， 24-hour urine output， monocyte chemoattractant protein-1 （MCP-1）， interleukin-12 （IL-12）， IL-10， advanced glycation end products （AGEs）， blood urea nitrogen （BUN） and serum creatinine （Scr） of mice were measured， and the ratio of bilateral kidneys to body weight was also calculated. The pathological injury and fibrotic changes of the renal cortex were observed， and the expressions of macrophage polarization marker proteins [type M1： inducible nitric oxide synthase （iNOS）； type M2： arginase-1 （Arg-1）] and AGEs-the receptor of advanced glycation end products （RAGE）/Ras homolog gene pharm_chenjing@163.com family member A （RhoA）/Rho-associated coiled-coil forming protein kinase （ROCK） signaling pathway-related proteins were determined in renal cortex. RESULTS Compared with the model group， the symptoms such as renal cortical hyperplasia， vacuoles， infiltration of inflammatory cells， and renal cortical fibrosis had been improved in GBE low-dose and high-dose groups； body weight， serum level of IL-10， the expression of Arg-1 in the renal cortex were significantly higher than model group （P＜ 0.01）； fasting blood glucose， 24-hour food intake， 24-hour urine output， serum levels of MCP-1， IL-12， BUN， Scr and AGEs， the ratio of bilateral kidneys to body weight， renal injury score， the proportion of renal interstitial fibrosis， the protein expressions of iNOS， RAGE， RhoA and ROCK1 （except for GBE low-dose group） in renal cortex were significantly lower than model group （P＜0.01）. CONCLUSIONS GBE could improve kidney damage and alleviate inflammatory response in DN model mice， the mechanism of which may be related to inhibiting the AGEs-RAGE/RhoA/ROCK signaling pathway and regulating macrophage polarization.
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AIM To investigate the effects of Ginkgo biloba extract on hearing function,cochlear morphology and autophagy-related protein expression in a rat model of presbycusis.METHODS Forty-five rats were randomly divided into the control group,the model group and the low,medium and high dose G.biloba extract groups(10,20 and 30 mg/kg),with 9 rats in each group.The rat model of presbycusis was established by intraperitoneal injection of 500 mg/kg D-galactose(D-gal).Eight weeks after the corresponding administration,the rats had their changes of hearing threshold detected by the auditory brainstem evoked potential(ABR);their morphological changes of cochlear hair cells,stria vascularis(SV)and spiral ganglion cells observed by HE staining;their number of hair cells inside and outside the cochlea detected by immunofluorescence staining;their ultrastructure changes of cochlear hair cells observed by transmission electron microscopy;and their expression of autophagy-related proteins in cochlea tissue detected by Western blot.RESULTS Compared with the control group,the model group displayed increased ABR threshold(P<0.01);more severely damaged inner and outer hair cells,spiral ganglion cells and SV,decreased SV thickness and numbers of spiral ganglion cells,inner and outer hair cells and autophagosomes(P<0.01);decreased protein expressions of Beclin1 and LC3 Ⅱ and ratio of LC3 Ⅱ/LC3 Ⅰ in cochlear tissue(P<0.01),and higher P62 protein expression(P<0.01).Compared with the model group,the medium and high dose G.biloba extract groups shared decreased ABR thresholds(P<0.01);improved morphology of inner and outer hair cells and SV in the cochlea,normalized,morphology of spiral ganglion cells,and increased SV thickness and the numbers of spiral ganglion cells,inner and outer hair cells and autophagosomes(P<0.05,P<0.01);increased protein expressions of Beclin1 and LC3 Ⅱ and the ratio of LC3 Ⅱ/LC3 Ⅰ in the cochlea(P<0.01),and decreased P62 protein expression(P<0.01).CONCLUSION The protective effects G.biloba extract on hearing function and cochlear cells in the rat model of presbycusis may be associated with the up-regulated expression of Beclin1 and LC3 Ⅱ proteins and down-regulated P62 protein expression in cochlear tissues.
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Background Arsenic exposure is a common and important environmental and occupational hazardous factor in China, and arsenic-induced insulin resistance (IR) has attracted widespread attention as a negative health outcome to the population. Objective To explore part of the mechanism of hepatic IR induced by arsenic exposure based on the peroxisome proliferators-activated receptors γ (PPARγ)/ glucose transporter 4 (GLUT4) pathway, and to investigate potential effects of Ginkgo biloba extract (GBE) on hepatic IR induced by arsenic exposure and associated mechanism of action. Methods The target of drug action was predicted by network pharmacology and verified by in vivo and in vitro experiments. In vivo experiments: 48 SPF C57BL/6J male mice were divided into 4 groups, including control group, 50 mg·L−1 NaAsO2 model group (NaAsO2), 50 mg·L−1 NaAsO2+10 mg·kg−1 GBE intervene group (NaAsO2+GBE), and 10 mg·kg−1 GBE group (GBE), 12 mice in each group. The animals were given free access to purified water containing 50 mg·L−1 NaAsO2, or given intraperitoneal injection of normal saline containing 10 mg·kg−1 GBE once per week. After 6 months of exposure, blood glucose detection, intraperitoneal glucose tolerance test (IPGTT), and insulin tolerance test (ITT) were performed. Serum and liver tissues were collected after the mice were neutralized, liver histopathological sections were obtained, serum insulin levels, liver tissue glycogen content, glucose content were detected by enzyme linked immunosorbent assay (ELISA), and the expression of PPARγ and GLUT4 proteins was detected by Western blot (WB). In vitro experiments: HepG2 cells were divided into 4 groups, including control group, 8 μmol·L−1 NaAsO2 group (NaAsO2), 8 μmol·L−1 NaAsO2 + 200 mg·L−1 GBE intervene group (NaAsO2+GBE), and 200 mg·L−1 GBE group (GBE). The levels of glycogen and glucose were detected by ELISA, and the expression of PPARγ and GLUT4 proteins was detected by WB. Results A strong binding effect between GBE and PPARγ was revealed by network pharmacology. In in vivo experiments, the NaAsO2 group exhibited an elevated blood glucose compared to the control group, and the NaAsO2+GBE group showed a decreased blood glucose compared to the NaAsO2 group (P<0.01). The histopathological sections indicated severe liver structural damage in the arsenic exposure groups (NaAsO2 group and NaAsO2+GBE group), with varying staining intensity, partial liver cell necrosis, and diffuse red blood cell appearance. Both results of in vitro and in vivo experiments showed a decrease in glycogen synthesis and glucose uptake in the NaAsO2 groups compared to the control groups, which was alleviated in the NaAsO2+GBE group (P<0.01). The results of WB revealed inhibited PPARγ expression and reduced GLUT4 levels on the cell membrane, and all these changes were alleviated in the NaAsO2+GBE group (P<0.01). Conclusion This study findings suggest that GBE antagonizes arsenic exposure-induced hepatic IR by regulating the PPARγ/GLUT4 pathway, indicating that GBE has a protective effect on arsenic exposure-induced hepatic IR, and PPARγ may be a potential therapeutic target for arsenic exposure-induced hepatic IR.
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Background Fluorine accumulates in the brain tissue after long-term excessive intake and subsequently cause nerve damage and decline of learning and memory ability. Receptor of advanced glycation end-products (RAGE)/p38 mitogen-activated protein kinase (p38MAPK)/nuclear factor kappa-B (NF-κB) signaling pathway is considered to be involved in the associated mechanism. Objective To study the changes of RAGE/ p38MAPK/ NF-κB signaling pathway in rats with subchronic fluorosis, and to explore the protective effects of extract of Ginkgo biloba 761 (EGb761) and RAGE antagonist (FPS-ZM1) on neuromemory ability. Methods Ninety male clean SD rats were divided into 9 groups with 10 rats in each group. The modeling period was 6 months. Control group (C group): free drinking tap water (fluoride content <0.5 mg·L−1), low- and high-dose fluoride groups (LF group, HF group): free drinking tap water with 10 or 50 mg·L−1 fluoride; intervention group of Ginkgo biloba extract (CE, LFE, and HFE groups): on the basis of the C group, LF group, and HF group, 100 mg·kg−1·d−1 EGb761 was given daily via intragastric administration; FPS-ZM1 intervention groups (CF, LFF, and HFF groups): 7 d before the end of modeling, 1 mg·kg−1·d−1 FPS-ZM1 was injected intraperitoneally daily on the basis of the C group, LF group, and HF group. The contents of fluoride in brain and blood of each group were detected. The learning and memory ability was tested by water maze experiment. The histopathologic changes of the hippocampus were detected by Nissl staining. The protein expression levels of RAGE and its ligand high mobility group protein B1 (HMGB1), NF-κB, p38MAPK, phospho-p38MAPK (p-p38MAPK), interleukin-6 (IL-6), and tumour necrosis factor-α (TNF-α) in brain tissue were detected by Western blotting. The mRNA expression levels of RAGE, HMGB1, and p38MAPK were detected by quantitative real-time PCR. Results Compared with the C group, the contents of blood fluoride and brain fluoride in the LF and the HF groups were increased (P<0.05). The results of the water maze experiment showed that, compared with the C group, the escape latency time of the LF group and the HF group was longer and the crossing times were reduced; compared with the HF group, the escape latency time of the HFE group and the HFF group was shortened, and the crossing times were increased (P<0.05). The Nissl staining results showed that the number of Nissl body in the HF group decreased compared with the C group; compared with the HF group, the number of Nissl body in the HFE group and the HFF group increased. The Western blotting results showed that compared with the relative protein expression levels of RAGE, HMGB1, NF-κB, p38MAPK, p-p38MAPK, IL-6, and TNF-α in the C group , the levels of above indicators in the HF group and the levels of RAGE, HMGB1, NF-κB, p-p38MAPK, and IL-6 in the LF group were up-regulated (P<0.05); compared with the HF group, the levels of above indicators in the HFE group and the HFF group were all down-regulated (P<0.05); compared with the relative protein expression levels of RAGE and HMGB1 in the LF group, the levels in the LFE group and the LFF group were all down-regulated (P<0.05). The quantitative real-time PCR results showed that compared with the C group, the mRNA expression levels of RAGE and HMGB1 in the LF group and the HF group were up-regulated; compared with the LF group, the mRNA expression levels of RAGE in the LFE group and the LFF group were down-regulated ; compared with the HF group, the mRNA expression levels of RAGE and HMGB1 in the HFE group and the HFF group were down-regulated (P<0.05). Conclusion The central nervous system injury caused by subchronic fluorosis may be related to the activation of RAGE/p38-MAPK/NF-κB signaling pathway, which can impair the learning and memory ability of rats, while EGb761 and FPS-ZM1 may have certain protective effects on the nerve injury.
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Post stroke cognitive impairment (PSCI) is the most common complication in stroke patients, which seriously affects their quality of life. Early comprehensive treatment to intervene in mild cognitive impairment caused by stroke is of great significance in reducing and delaying the occurrence of dementia. This is a review on the latest treatment progress of PSCI.
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ABSTARCT AIM: To investigate the effect of Ginkgo biloba extract (GBE) on kidney injury in rats with chronic renal failure (CRF) and its potential molecular mechanism. METHODS: SD rats were given 5/6 nephrectomy to construct CRF models and divided into model group, GBE group (100 mg /kg), GBE+ Agomir-NC group, and GBE+Agomir-145 group, 12 per group; another 12 were selected as the sham group, with only the kidney exposed and no nephrectomy. Rats in the GBE group were given GBE 100 mg/kg gavage daily, once a day, for 4 consecutive weeks; rats in the GBE+Agomir-NC group and GBE+Agomir-145 group were given GBE 100 mg/kg gavage daily, and then Agomir-NC and Agomir-145 were injected via the tail vein every 3 days for 4 weeks; the sham group and the model group were given the same amount of normal saline by gavage and injection through the tail vein respectively. The general state of the rat was observed, and the renal function indicators [24 h urine microalbumin (24 h UAlb), blood urea nitrogen (BUN), blood creatinine (SCr)] and oxidative stress indicators [malonaldehyde (MDA), Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px)] were detected, Masson staining was used to observe the fibrosis of kidney tissue, real-time fluorescent quantitative PCR (RT-qPCR) was used to detect the mRNA expression levels of microRNA-145 (miR-145), transforming growth factor - β1 (TGF - β1) and forkhead box O1 (FOXO1) in renal tissue, Western blot was used to detect the protein levels of TGF - β1 and FOXO1 in kidney tissue. RESULTS: The general state of CRF rats improved significantly after GBE intervention, the body weight, renal tissue SOD and GSH-Px activities, and FOXO1 mRNA and protein levels were significantly higher than those in the model group (P<0.05); the 24 h UAlb, serum BUN, SCr and renal tissue MDA levels, the relative area of renal interstitial fibrosis, and renal tissue miR-145, TGF - β1 mRNA and protein levels were significantly lower than those in the model group (P<0.05); and on the basis of GBE intervention, up-regulating the expression of miR-145 could significantly weaken the protective effect of GBE on renal injury in CRF rats (P<0.05). CONCLUSION: GBE can alleviate kidney damage in CRF rats, and its mechanism of action may be related to down-regulation of miR-145, up-regulation of FOXO1 expression, and inhibition of renal fibrosis.
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Depression is a mental disorder with high morbidity, disability and relapse rates. Ginkgo biloba extract (GBE), a traditional Chinese medicine, has a long history of clinical application in the treatment of cerebral and mental disorders, but the key mechanism remains incompletely understood. Here we showed that GEB exerted anti-depressant effect in mice through regulating gut microbial metabolism. GBE protected against unpredictable mild stress (UMS)-induced despair, anxiety-like and social avoidance behavior in mice without sufficient brain distribution. Fecal microbiome transplantation transmitted, while antibiotic cocktail abrogated the protective effect of GBE. Spatiotemporal bacterial profiling and metabolomics assay revealed a potential involvement of Parasutterella excrementihominis and the bile acid metabolite ursodeoxycholic acid (UDCA) in the effect of GBE. UDCA administration induced depression-like behavior in mice. Together, these findings suggest that GBE acts on gut microbiome-modulated bile acid metabolism to alleviate stress-induced depression.
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Humanos , Ratones , Animales , Depresión/tratamiento farmacológico , Microbioma Gastrointestinal , Extractos Vegetales , Ginkgo bilobaRESUMEN
Ginkgo biloba Extract( GBE50) Dispersible Tablets is a new standardized prescription,which is widely used in the treatment of ischemic cardiovascular and cerebrovascular diseases. However,there are still many problems in its clinical application.Rational and safe use of GBE50 Dispersible Tablets is pivotal to the medication safety and clinical prognosis of patients. This consensus has been jointly formulated by clinical experts of traditional Chinese medicine and western medicine in cardiovascular and cerebrovascular diseases and followed the Manual for the Clinical Experts Consensus of Chinese Patent Medicine published by the China Association of Chinese Medicine. The present study identified clinical problems based on clinical investigation,searched the research papers according to PICO clinical problems,carried out evidence evaluation,classification,and recommendation by GRADE system,and reached the expert consensus with nominal group technique. The consensus combines evidence with expert experience. Sufficient evidence of clinical problems corresponds to " recommendations",while insufficient evidence to " suggestions". Safety issues of GBE50 Dispersible Tablets,such as indications,usage and dosage,and medication for special populations,are defined to improve clinical efficacy,promote rational medication,and reduce drug risks. This consensus needs to be revised based on emerging clinical issues and evidencebased updates in practical applications in the future.
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Humanos , Trastornos Cerebrovasculares/tratamiento farmacológico , Consenso , Medicamentos Herbarios Chinos/uso terapéutico , Medicina Tradicional China , ComprimidosRESUMEN
The present study aimed to systematically evaluate the efficacy and safety of Ginkgo biloba extract 50(GBE50) in the treatment of ischemic stroke. The databases including CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, and Cochrane Library were searched for randomized controlled trial(RCT) of GBE50 for the treatment of ischemic stroke reported between database inception and May 2020. The methodological quality of the included RCTs was evaluated via the Cochrane risk of bias tool. The RevMan 5.4 was used for Meta-analysis. Sixteen RCTs were included, involving 1 615 patients with acute ischemic stroke. Most of the included RCTs reported the methods of random sequence generation, but only two performed the concealment of random sequence. All RCTs failed in blinding. Two RCTs reported the information of cases lost to follow-up and drop-outs. Since the number was small, the baselines of groups remained balanced. All RCTs reported key outcomes of ischemic stroke, which made selective reporting bias in a low risk. Meta-analysis results revealed that GBE50 combined with routine therapies could effectively lower the score of the National Institutes of Health stroke scale(NIHSS) and restore cognitive function and daily activity in ischemic stroke patients. Compared with routine therapies, the combination is advantageous in treating patients with ischemic stroke. However, high-quality multicenter RCTs with large sample sizes are still required for verification.
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Humanos , Isquemia Encefálica/tratamiento farmacológico , Ginkgo biloba , Accidente Cerebrovascular Isquémico , Estudios Multicéntricos como Asunto , Extractos Vegetales , Accidente Cerebrovascular/tratamiento farmacológicoRESUMEN
Objective To investigate the effect of Ginkgo biloba extract on behaviors in rat with adolescent sedentariness and its possible mechanism. Methods Twenty-four male SD rats (4-week-old) were randomly divided into normal control (NC), adolescent sedentarines (AS), and Ginkgo biloba extract (GBE) groups. After 4 weeks intervention with GBE, open-field test and elevated plus-maze test were performed to detect the behavioral changes. The content of malondialdehyde (MDA) and activity of superoxide dismutase (SOD) in brain were determined by colorimetric method. Protein levels of glycogen synthase kinase 3β(GSK-3β) and β-catenin in cerebral white matter were determined by Western blotting. Results In open-field test, it was shown that the autonomic activity of rats in AS group increased, while the central regional travel time was reduced. Duration and number of residence in the open arm of elevated plus-maze test decreased in AS group. These anxiety-like behaviors were ameliorated by GBE intervention. Compared with the NC group, GSK-3β/ β-catenin ratio and the content of MDA was upregulated in AS group while downregulated in GBE group. And activity of SOD were downregulated in AS group while significantly upregulated in GBE group (P<0. 05). Conclusion Ginkgo biloba extract ameliorate anxiety-like behavior in rat with adolescent sedentariness. Wnt/ β-catenin pathway and antioxidant regulation may play a cerebral protective role.
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This study aimed to assess the effects of Ginkgo Biloba Extract and Troxerutin on the hippocampus of induced diabetes mellitus in adult albino rats using histological methods.50 adult male albino rats were divided into three groups; Group I (Control); Group II (diabetic): subdivided into Subgroup IIa (T1DM)), Subgroup IIb (T1DM+GBE), Subgroup IIc (T1DM+ troxerutin); Group III: subdivided into Subgroup IIIa (GBE) and Subgroup IIIb (troxerutin). The brain was removed and the cerebral hemisphere was coronally cut at the hippocampal level and used for light microscopic study (H&E staining and PCNA immunostaining). There was a statistically insignificant improvement in animal weights in subgroup IIb and subgroup IIc. Subgroup IIb showed a statistically significant reduction of blood glucose levels while the subgroup IIc showed insignificant reduction of blood glucose levels. Diabetes disturbed the light microscopic structure of the hippocampus. In subgroup IIb and subgroup IIc the hippocampus retained an apparently normal appearance and the stratum pyramidale exhibited the pyramidal cells with rounded vesicular nuclei and acidophilic cytoplasm. Diabetic hippocampal sections revealed negative PCNA immunoreactivity inall layers of DG. In subgroup IIb and subgroup IIc, hippocampal sections showed positive immunoreactivity
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@#To explore the effect of Ginkgo biloba extract (GBE) on anticoagulation of 4 new oral anticoagulants (NOACs), dabigatran, apixaban, rivaroxaban and edoxaban in vitro, thrombin time (TT), prothrombin time (PT), activated partial thrombin time (APTT) and the activity of coagulation factor Xa (FXa) of rat plasma were measured at different concentrations of NOACs, GBE or NOACs combined with GBE, respectively. The results showed that TT, PT and APTT were prolonged with the increase of NOACs concentration in the range of 0-500 ng/mL; that except for TT of rivaroxaban, other results showed a good linear correlation with NOACs concentration (r2= 0.78-0.98); and that FXa activity decreased with increased concentration of FXa inhibitors (apixaban, rivaroxaban and edoxaban), with a good linear correlation with concentration of FXa inhibitors in the range of 0-250 ng/mL (r2= 0.85-0.94). GBE had no significant effect on TT, PT and APTT (P>0.05) in the concentration range of 0-500 μg/mL, but FXa activity had a positive linear correlation with GBE concentration (r2= 0.840 4). TT was prolonged with increasing GBE concentration when dabigatran was combined with GBE. When the above FXa inhibitors were combined with GBE, TT shortened and FXa activity increased with rising GBE concentration. There were no significant changes in PT and APTT (P>0.05) when NOACs were combined with GBE. The study results suggest that GBE may synergize with the anticoagulant activity of dabigatran and antagonize the anticoagulant activity of FXa inhibitors, possibly due to its role in increasing FXa activity.
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OBJECTIVE：To rapidly evaluate the effectiveness ，safety and economics of Ginkgo biloba extract（EGb）in the treatment of Alzheimer ’s disease （AD）patients，and to provide evidence-based reference for clinical drug selection and decision. METHODS：Retrieved from PubMed ，Embase，Cochrane Library ，Web of Science ，CNKI，CBM，Wanfang database ，health technology assessment （HTA）organization websites and database during the inception to Aug. 10，2020，HTA reports ，systematic reviews/Meta-analysis，and pharmacoeconomic studies of EGb versus placebo in the treatment of AD were collected. After literature screening and data extration ，HTA checklist ，AMSTAR-2 scale and CHEERS scale were used respectively to evaluate the literature quality of the included HTA report ，systematic review/Meta-analysis and pharmacoeconomics studies. The conclusion of the included studies were summarized by using qualitative description. RESULTS ：A total of 9 literatures were included ，involving 8 systematic reviews and 1 economic studies. In terms of effectiveness ，there was no statistical significance in MMSE score of EGb group，ADAS-Cog score of 120 mg EGb group ，compared with placebo group （P＞0.05）. Dementia Quality of Life （DQoL）score of EGb group was significantly higher than that of placebo group. The scores of short cognitive aptitude tests ，neuropsychiatric inventory（NPI），NPI caregiver version score ，ADAS-Cog score of 160 mg EGb group and 240 mg EGb group were significantly lower than those of control group （P＜0.05）. ADL scores of patients were inconsistent ；ADL scores of EGb group were significantly lower than those o f placebo group （P＜0.05），or there was no significant diff erence between 2 groups（P＞0.05）； . subgroup analysis by dose showed that there was no RDY2019-39） significant difference in ADL score between 120 mg EGb group and placebo group （P＞0.05）；ADL score of 240 mg E-mail：renxiaolei83@126.com EGb group were signicantly lower than that of placebo group （P＜0.05）. Subgroup analysis of clinical global impression 010-88325751。E-mail：lyi1267@126.com change （CGIC） score showed that there was no significant difference in CGIC score between EGb group and placebo group after receiving ＜200 mg EGb and 26 weeks of treatment （P＞ 0.05）；CGIC score of EGb group was significantly higher than that of placebo group after receiving ＞200 mg EGb and 24 weeks of treatment （P＜0.05）. In terms of safety ，there was no statistical significance in the incidence of ADR or the incidence of severe ADR between EGb group and placebo group （P＞0.05）. Subgroup analysis by dose showed that the incidence of ADR in 240 mg EGb group was significantly higher than placebo group （P＜0.05）. Economically ，EGb treatment for AD is cost-effective ，which could indirectly save the nursing costs of AD patients. CONCLUSIONS ：The efficacy of EGb in the treatment of AD is uncertain ， and the safety and economy are good.
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Ginkgo biloba is a kind of ancient relict woody. It is a common homologous plant of medicine and food. Its leaves and fruits can produce secondary metabolites, such as flavonoids and ginkgolide, which have good medicinal effects. Ginkgo biloba leaves have low toxicity and broad-spectrum pharmacological activity. The research showed that ginkgo flavonoid has the effect of anticancer and cancer prevention. It is a potential chemical for cancer prophylaxis, which can significantly reduce the incidence of many malignant cancers. The progress in research on the structures, antitumor effects, and mechanism of flavonoids of Ginkgo biloba is summarized in this article, which provides a pharmacological basis for the deep processing and comprehensive utilization of Ginkgo biloba.
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To investigate if ginkgo biloba extract (Egb-761) can improve tardive dyskinesia (TD) symptoms through increasing the activity of plasma MnSOD. Methods We enrolled a total of 384 schizophrenia patients including 157 TD patients and 227 non-TD patients, as well as 280 normal subjects. The difference of MnSOD level in plasma among these groups were compared. TD patients were then randomly divided into two groups. The treatment group (n=77) and the placebo group (n=75) were treated with 240 mg of Egb-761 or placebo per day for 12 weeks, respectively. The abnormal involuntary movement scale (AIMS) and the positive and negative symptoms scale (PANSS) were used to evaluate the severity of the symptoms in baseline, the sixth week and the twelfth week after treatment. The level of MnSOD activity in plasma was also detected before and after the treatment. Results The level of MnSOD activity was lower in schizophrenia groups than in healthy control group (P＜0.01). In addition, the level of MnSOD activity was significantly lower in TD group than in non-TD group (P＜0.05). Repeated measures analysis of variance showed that group effect (F=4.00, P=0.05), time effect (F=32.17, P＜0.01) and interactive effect of group and time (F=39.04, P＜0.01) were significant in AIMS total score. The AIMS total score of treatment group was significantly lower than that of placebo group at 6-week and 12-week time points (all P＜0.01). Repeated measures analysis of variance showed that time effect (F=23.04, P＜0.01) and interactive effect of group and time (F=6.41, P＜0.05) were significant in the level of MnSOD activity. In addition, the level of MnSOD at baseline was significantly correlated with the reduction of AIMS total score during the treatment period (r=0.27, P=0.018). Conclusion Treatment of Egb-761 can improve symptoms of TD and activity of MnSOD.
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Objective: To observe the effect of Ginkgo biloba extract on cerebral cortical ischemia in mice with acute cerebral ischemia and explore its effect on Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) pathway. Methods: Sixty adult healthy male CD1 mice were randomly divided into sham operated group, model group, positive control group (3 × 104 IU/kg ulinastatin) and Ginkgo biloba extract low, medium and high doses (10, 20, 40 mg/kg) groups. The acute cerebral ischemia model in other five groups were all established except sham operated group. After successful modeling, mice in each group were given corresponding drugs iv tail, sham operation group and model group were given the same amount of saline. The pathological changes and histological grades of the cerebral cortex were observed. The survival neuron density of each group was compared. Malondialdehyde (MDA) and superoxide dismutase (SOD) were measured by colorimetry and xanthine oxidation respectively. The expressions of Toll like receptor 4 (TLR4) and nuclear transcription factor NF-κB p65 (NF-κB p65) mRNA were detected by real-time fluorescent quantitative PCR (qRT-PCR). Western blotting was used to detect TLR4 and NF-κB p65 protein expression. Results: In sham-operated group, the structure of cerebral cortex was normal, and the cells were full and arranged tightly and orderly. In the blank control group, the structure of cerebral cortex was severely damaged, and the cells were severely shrunk and disordered. Pathological changes in the Ulinastatin group and Ginkgo biloba extract groups were alleviated and dose-dependent. Compared with the sham operation group, the other five groups showed higher histological grade and MDA level in cerebral cortex (P < 0.05). Compared with the model group, the histological grade and MDA level of cerebral cortex decreased in ulinastatin group and Ginkgo biloba extract groups (P < 0.05). Compared with ulinastatin group, the histological grade and MDA content of brain cortex decreased in high dose group (P < 0.05). Compared with the sham operated group, the density of surviving neurons and the level of SOD in the other five groups decreased (P < 0.05). Compared with the model group, the density of survival neurons and the level of SOD in cortex increased in ulinastatin group and Ginkgo biloba extract group (P < 0.05). Compared with ulinastatin group, the density of survival neurons and the level of SOD in cortex increased in high dose group (P < 0.05). Compared with the sham operated group, the expression of TLR4, NF-κB p65 mRNA and protein in the other five groups increased (P < 0.05). Compared with the model group, the expression of TLR4, NF-κB p65 mRNA and protein in cortex of mice in ulinastatin group and Ginkgo biloba extract group decreased (P < 0.05). Compared with ulinastatin group, the expression of TLR4, NF-κB p65 mRNA and protein in the brain cortex of mice decreased in the high dose group (P < 0.05). Conclusion: Ginkgo biloba extract can alleviate the pathological changes caused by cerebral ischemia in mice with acute cerebral ischemia, alleviate neurological impairment, and improve oxidative stress indexes of cerebral cortex tissues. It is presumed that it may be achieved by regulating TLR4/NF-κB p65 signaling pathway and inhibiting the expressions of TLR4 and NF-κB p65 proteins.
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Objective To observe the clinical effect of treating Alzheimer's disease (AD) using transcranial magnetic stimulation.Methods One hundred and ninety-six patients with Alzheimer's disease were randomly divided into an observation group and a control group,each of 98.The observation group was given transcranial magnetic stimulation of the left and right dorsolateral frontal lobes of the brain and simultaneously given "8-shaped" coil stimulation.The stimulation intensity was 80％ of the motor threshold with a sequence of 2 s of stimulation at 5 Hz and 30 s rest for 30 min in each session.There were two sessions a day for 28 days.The control group was treated with identical pseudo-stimulation.Moreover,both groups were treated with intravenous injections of 20 ml of Ginkgo biloba extract dissolved in 250 ml of sodium chloride,or in the control group a glucose injection,one daily for two weeks.Before and after the treatment,the cognition,behavior and neuropsychological symptoms of both groups were evaluated using the mini mental state examination scale (MMSE),the AD rating scale (ADAS-cog),the activity of daily living (ADL) scale,a neuropsychiatric questionnaire (NPI) and an AD behavioral pathology rating scale (BEHAVE-AD) to compare the clinical effects.Results There were no significant differences in the groups' average scores on any of the evaluations before the treatment.After the treatment,the average MMSE and ADAS-cog scores in both groups had improved significantly,but with significantly greater improvement in the observation group.After the treatment,the average ADL,NPI and BEHAVE-AD scores of the observation group and the average ADL score of the control group were significantly lower than before the treatment.No significant differences were observed in the average NPI and BEHAVE-AD scores of the control group.After the intervention,the average ADL,NPI and BEHAVE-AD scores in the observation group were significantly lower than those of the control group.The total effectiveness rate of the observation group (90.8％) was significantly higher than that of the control group (62.2％).Conclusion Transcranial magnetic stimulation can significantly improve the cognitive,behavioral and neuropsychological status of patients with Alzheimer's disease.
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OBJECTIVES.: Sodium salicylate (SS) is well known for its ototoxic properties that induce functional and morphological changes in the cochlea and brain. Ginkgo biloba extract (GBE) has been widely used for treatment of various neurodegenerative diseases; however, its effects on salicylate-induced ototoxicity remain unclear. Herein, we examined the effects of EGb 761 (EGb), a standard form of GBE, on the plasticity of the N-methyl-D-aspartate receptor subunit 2B (GluN2B) in the inferior colliculus (IC) following SS administration. METHODS.: Seven-week-old Sprague Dawley rats (n=24) were randomly allocated to control, SS, EGb, and EGb+SS groups. The SS group received a single intraperitoneal SS injection (350 mg/kg), the EGb group received EGb orally for 5 consecutive days (40 mg/kg), and the EGb+SS group received EGb for 5 consecutive days, followed by an SS injection. The auditory brainstem responses (ABRs) were assessed at baseline and 2 hours after SS administration. GluN2B expression was examined by Western blot and immunohistochemistry. RESULTS.: There were no significant differences in ABR threshold shifts among the groups. The expression of the GluN2B protein normalized by which of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was significantly lower in the EGb+SS group, as compared to the SS group (P=0.012). Weak and diffused GluN2B immunoreactivity was detected in the IC neural cells of the EGb+SS group, while those of the SS group exhibited strong and diffused GluN2B positivity. CONCLUSION.: EGb may play a role in regulating the GluN2B expression in the IC of salicylate-induced ototoxicity model.
Asunto(s)
Western Blotting , Encéfalo , Cóclea , Potenciales Evocados Auditivos del Tronco Encefálico , Ginkgo biloba , Gliceraldehído 3-Fosfato , Inmunohistoquímica , Colículos Inferiores , N-Metilaspartato , Enfermedades Neurodegenerativas , Oxidorreductasas , Plásticos , Ratas Sprague-Dawley , Salicilato de SodioRESUMEN
OBJECTIVE: To develop on-line high performance liquid chromatography-biochemical detection (HPLC-BCD) METHODS: to screen effective components in Ginkgo biloba extract for treatment of Alzheimer's disease.METHODS: Radical scavengers and AchE inhibitors in G.biloba leave extract were screened by HPLC-UV-DPPH/ABTS and HPLC-UV-AchE METHODS:, respectively. The stability and repeatability of the on-line HPLC-UV-AchE method were investigated using galanthamine as a positive reference. The main active ingredients in the extract were identified by ultra high performance liquid chromatography linear ion trap/orbitrap high resolution mass spectrometry (UPLC-LTQ/orbitrap MS) method. RESULTS: Fourteen antioxidants in G.biloba extract were detected by the HPLC-UV-DPPH/ABTS method, while three AchE inhibitors were found by the HPLC-UV-AchE method. The three AchE inhibitors were tentatively identified by UPLC-LTQ/orbitrap MS as 4-O-beta-glucopyranosyl-cis-coumaric acid ginkgolide A and 3-O-[2-O-(β-D-Glucosyl)-α-L-rhamnosyl]quercetin, respectively. CONCLUSION: The proposed on-line HPLC-BCD method shows high sensitivity, good repeatability and stability. It can be used to screen antioxidants and AchE inhibitors in G. biloba extract. This will provide an effective, quick and convenient analysis tool to quickly find bioactive ingredients of traditional Chinese medicines for treating related diseases.
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@#Objective To investigate the potential effect and molecular mechanism of ginkgo biloba extract (GBE) on the expression of inflammatory factors in liver tissue of mice poisoned by xylene. Methods A total of 30 clean grade healthy Kunming mice were randomly divided into normal control group, model group and ginkgo biloba extract intervention group (GBE group). Mice of three groups were granted free access to food and water. The concentration of xylene inhalation was 110-130 mg/m3 (the air samples were collected in the box, and the gas chromatogram was measured by direct injection method) in model group and GBE group. The mice in control group inhaled air. GBE group was intraperitoneally injected with 50 mg/(kg·d) of GBE. Control and model groups were intraperitoneal injected with same amount of normal saline. After 8 weeks, mice were sacrificed, and serum and liver tissues were retained. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), alkaline phosphatase (ALP) and glutamyl transpeptidase (GGT) were measured. Haematoxylin and Eosin staining was used to observe pathological changes of liver tissue. RT-PCR and Western blot assay were used to detect the expression levels of nuclear factor kappa B (NF-κB), tumor necrosis factor alpha (TNF-α) mRNA and protein in liver tissue. Results Compared with the control group, the liver tissue was damage seriously in the model group. The blood biochemical indexes (ALT, AST, TBIL, ALP and GGT) were significantly increased (P＜0.05), and the NF-κB, TNF-α mRNA and protein were significantly increased in the model group (P＜0.05). Compared with the model group, the liver tissue damage was reduced, the blood biochemical indexes (ALT, AST, TBIL, ALP and GGT) were significantly decreased (P＜0.05) and the NF-κB, TNF-α mRNA and protein were significantly down-regulated in the GBE group (P＜0.05). Conclusion Ginkgo biloba extract can reduce hepatic inflammatory response of mice poisoned by xylene through inhibiting the expression of NF-κB and TNF-α inflammatory factors.