Ginkgo Leaf Tablet Research Articles

Synthesis of silver nanoclusters using a double-stranded DNA template and its application for captopril detection

The purpose of this study was to explore the feasibility and mechanism of synthesizing silver nanoclusters (AgNCs) using a double-stranded DNA (dsDNA) template and to use the AgNCs as probes for captopril detection. The results showed that the binding of silver ions towards DNA bases deduced the destruction of the initial dsDNA structure, and AgNCs with decent quantum yield (43.54%) were obtained. The detection using these AgNCs probes showed good performance for captopril, with a linear range of 0.1–0.8 μg·mL−1 and a detection limit of 0.045 μg·mL−1. Recovery results in real samples of Apocynum venetum leaf tea and Ginkgo biloba leaf tablet demonstrated its good applicability. This work not only extended the understanding of DNA-AgNCs but also provided a fast and cost-effective tool for captopril detection.

Effect of ginkgo leaf tablets combined with compound carbidopa on patients with Parkinson’s disease

Purpose: To determine the effect of a combination of ginkgo leaf tablets with compound carbidopa tablets on cognitive function, serum homocysteine (Hcy), malondialdehyde (MDA) and neuron-specific enolase (NSE) levels in patients with Parkinson's disease (PD).Methods: A total of eighty (80) PD patients admitted to The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China between December 2020 and December 2022 were randomly divided into two groups: Western medicine group (n = 40, using compound carbidopa tablets alone) and combination group (n = 40, using ginkgo leaf tablets combined with compound carbidopa tablets), and orally treated for 3 months. Mini-mental state examination (MMSE) and Montreal Cognitive Assessment (MoCA) were used to assess cognitive function before and after treatment. High-performance liquid chromatography was used to determine serum Hcy levels, while enzyme-linked immunosorbent assay (ELISA) was used to evaluate serum MDA and NSE levels. Adverse reactions were also recorded during treatment.Results: Total response rate following treatment in combination group was significantly higher than in Western medicine group (95.00 vs 80.00 %, p < 0.05). After treatment, MMSE and MoCA scores in combination group were significantly higher (p < 0.05) than those in Western medicine group, while serum Hcy, MDA and NSE levels in combination group were significantly lower than those in Western medicine group (p < 0.05). During treatment, there was no significant difference in incidence of adverse reactions between the two groups (p > 0.05).Conclusion: Ginkgo leaf tablets in combination with carbidopa significantly improve cognitive functions associated with PD with high safety, when compared to carbidopa tablets alone. However, further clinical trials are commended to validate these findings.

Effects of ginkgo leaf tablet on the pharmacokinetics of rosiglitazone in rats and its potential mechanism

Context Ginkgo leaf tablet (GLT), a traditional Chinese herbal formula, is often combined with rosiglitazone (ROS) for type 2 diabetes mellitus treatment. However, the drug-drug interaction between GLT and ROS remains unknown. Objective To investigate the effects of GLT on the pharmacokinetics of ROS and its potential mechanism. Materials and methods The pharmacokinetics of 10 mg/kg ROS with 100/200 mg/kg GLT as single-dose and 10-day multiple-dose administration were investigated in Sprague-Dawley rats. In vitro, the effects of GLT on the activity of CYP2C8 and CYP2C9 were determined in recombinant human yeast microsomes and rat liver microsomes with probe substrates. Results The t 1/2 of ROS increased from 2.14 ± 0.38 (control) to 2.79 ± 0.37 (100 mg/kg) and 3.26 ± 1.08 h (200 mg/kg) in the single-dose GLT administration. The AUC0-t (139.69 ± 45.46 vs. 84.58 ± 39.87 vs. 66.60 ± 15.90 h·μg/mL) and t 1/2 (2.75 ± 0.70 vs. 1.99 ± 0.44 vs. 1.68 ± 0.35 h) decreased significantly after multiple-dose GLT treatment. The IC50 values of quercetin, kaempferol, and isorhamnetin, GLT main constituents, were 9.32, 7.67, and 11.90 μmol/L for CYP2C8, and 27.31, 7.57, and 4.59 μmol/L for CYP2C9. The multiple-dose GLT increased rat CYP2C8 activity by 44% and 88%, respectively. Discussion and conclusions The metabolism of ROS is attenuated in the single dose of GLT by inhibiting CYP2C8 and CYP2C9 activity, and accelerated after the multiple-dose GLT treatment via inducing CYP2C8 activity in rats, indicating that the clinical dose of ROS should be adjusted when co-administrated with GLT.

Effect of cognitive rehabilitation training combined with butylphthalide soft capsules and ginkgo-leaf tablets on patients with mild Alzheimer's disease

Purpose: To study the impact of a combination of cognitive rehabilitation training, butylphthalide soft capsules and ginkgo-leaf tablets on patients with mild Alzheimer’s disease (AD).Methods: One hundred and twenty-eight (128) mild AD patients were randomly assigned to medication treatment group (MT group, n = 64) and joint training group (JT group, n = 64). Both groups were treated with butylphthalide soft capsules and ginkgo-leaf tablets, while the JT group additionally received cognitive rehabilitation training. Therapeutic effects and adverse drug reactionsin the two groups were assessed.Results: Total effectiveness was significantly higher in JT patients (84.38 %) than in MT patients (60.94 %; χ2 = 8.9320). After treatment, Mini-Mental State Exam (MMSE), Activity of Daily Living (ADL) and ADAS-cog scores in the JT group were significantly better than those in the MT group, (p < 0.05). There were significantly lower plasma NO, serum VEGF and MDA levels in JT patients than in MT patients. CRP and Hcy levels were markedly lower in JT than in MT patients. The incidence of adverse reactions in both groups was comparable (p > 0.05).Conclusion: Rehabilitation training in combination with butylphthalide soft capsule and ginkgo-leaf tablets produce significant therapeutic impact on mild AD patients. The combination therapy delays cognitive decline and memory loss in AD patients, improves their serological indicators, and lowers the incidence of adverse reactions.

Systematic review and Meta-analysis of clinical efficacy and safety of Ginkgo Leaf Tablets in treatment of acute cerebral infarction

To systematically evaluate the clinical efficacy and safety of Ginkgo Leaf Tablets(GLT) in the treatment of acute cerebral infarction(ACI). Seven databases both at home and abroad were systematically retrieved from their establishment to March 2020. The data of the included studies were extracted after review and screening. The quality of the included studies was assessed with the Cochrane risk bias assessment tool, and then the included studies were put into Meta-analysis by RevMan 5.3 to evaluate the total cli-nical efficiency, neurological function score, blood lipids and incidence of adverse reactions in treatment of ACI by GLT. Finally, the GRADE system was adopted to evaluate the evidence quality of each outcome indicator and form recommendations. Ten studies involving 886 participants were included, all of which were of low quality. Meta-analysis results showed that,(1)in terms of the total clinical efficiency, GLT+Western medicine was superior to Western medicine alone(RR_(NDS)=1.20, 95%CI[1.06, 1.36], P=0.005; RR_(NIHSS)=1.35, 95%CI[1.09, 1.69], P=0.007), and there was no statistical difference between GLT+Xuesaitong Injection+Wes-tern medicine and Xuesaitong Injection+Western medicine(RR=1.16, 95%CI[1.00, 1.35], P=0.05).(2)In terms of improving neurological function score, GLT+Western medicine was superior to Western medicine alone(MD_(NIHSS[moderate(severe)])=-1.55, 95%CI[-2.22,-0.88], P<0.000 01; MD_(NIHSS(severe))=-7.51, 95%CI[-8.00,-7.02], P<0.000 01; MD_(NDS)=-1.36, 95%CI[-2.39,-0.33], P=0.01), and GLT+Danshen Injection+Western medicine was superior to Danshen Injection+Western medicine(MD_(NDS)=-3.09, 95%CI[-3.84,-2.34], P<0.000 01).(3)In terms of regulating blood lipids, GLT+Western medicine was superior to Wes-tern medicine alone(MD_(TC)=-1.40, 95%CI[-2.13,-0.66], P=0.000 2; MD_(TG)=-1.29, 95%CI[-1.86,-0.73], P<0.000 01; MD_(LDL-C)=-1.48, 95%CI[-2.91,-0.04], P=0.04; MD_(HDL-C)=0.07, 95%CI[0.02, 0.12], P=0.009).(4)In terms of incidence of adverse reactions, there was no statistical difference between GLT+Western medicine and Western medicine alone(RR=0.63, 95%CI[0.30, 1.32], P=0.22). The results of the evaluation showed that the evidence level of each outcome indicator was low, and the recommendation was at weak level. In conclusion, GLT+Western medicine could improve the total clinical efficiency, neurological function score, and blood lipid status, with a low incidence of adverse reactions. However, due to the small amount of included stu-dies, low study quality and low level of evidence, it is expected to carry out clinical studies with standardized design and large sample size in the future to further investigate the clinical efficacy and safety of GLT in the treatment of ACI.

Adjusting Antithrombotic Therapy after Stent Implantation for Acute Myocardial Infarction in a Patient with Very Low Platelet

A 76-year-old woman presented with non-ST-elevation myocardial infarction. Platelet count was 10×109/L. Bone marrow cytology and platelet antibody testing 9 months earlier suggested refractory immune thrombocytopenia (unresponsive to glucocorticoid and γ-globulin). The patient stabilized after treatments that included clopidogrel, statin, nitrate, and conventional anti-heart failure drugs, but heart failure persisted. Nine days later, angiography revealed 90% occlusion in the left anterior descending artery, and the patient received a zotarolimus-eluting stent. Upon discharge from the hospital, the patient started to receive clopidogrel, statin, β-blocker, and spironolactone. The patient remained free from the symptoms and reported no signs of bleeding for the next 8 months until she was readmitted for pneumonia and heart failure. Platelet count at this time was 2×109/L. Clopidogrel was discontinued. Ginkgo leaf tablets (an herbal medication with reported activity against platelet aggregation) were initiated. Subsequent follow-up visits were unremarkable, until 16 months after percutaneous coronary intervention, when platelet count decreased to 1×109/L. Ginkgo leaf tablet was discontinued. In summary, the evidence supporting the efficacy of clopidogrel at shorter than the recommended 12 months is anecdotal, but the need to adjustment dual antiplatelet therapy in patients with very low platelet count is solid.

Effects of Ginkgo leaf tablets on the pharmacokinetics of atovastatin in rats

Context: Ginkgo leaf tablets (GLT), an effective traditional Chinese multi-herbal formula, are often combined with atorvastatin calcium (AC) for treating coronary heart disease in clinic.Objective: This study investigated the effects of GLT on the pharmacokinetics of AC and the potential mechanism.Materials and methods: The pharmacokinetics of AC (oral administered at a dose of 1 mg/kg) with or without pre-treatment of GLT (oral administered at a dose of 80 mg/kg/day for 10 days) were investigated in male Sprague–Dawley rats. The effects of GLT on the metabolic stability of AC were also investigated using rat liver microsome incubation systems.Results: The results indicated that the Cmax increased from 36.84 ± 4.21 to 48.68 ± 6.35 ng/mL, and the AUC(0-t) increased from 135.82 ± 21.05 to 77.28 ± 12.92 ng h/mL, and t1/2 also increased from 2.62 ± 0.31 to 3.32 ± 0.57 h when GLT and AC were co-administered. The metabolic stability of AC was also increased (48.2 ± 6.7 vs. 36.7 ± 5.3 min) with the pre-treatment of GLT.Discussion: This study indicated that the main components in GLT could accelerate the metabolism of AC in rat liver microsomes and change the pharmacokinetic behaviours of AC. So these results showed that the herb-drug interaction between GLT and AC might occur, and the clinical efficacy could increase when they were co-administered. Therefore, the clinical dose of AC should be decreased when GLT and AC are co-administered.

Effects of notoginseng and ginkgo leaf tablets on cardiac function and serum inflammatory factors in hypoxia deacclimatized rats and its mechanism

To study the effects of notoginseng, gingko leaf and rhodiola on cardiac functions and the serum inflammatory factors interleukin-6,interleukin-10, and TNF-α of rats with hypoxia deacclimatization, to explore the mechanism of hypoxia detoxification. Forty SD rats were randomly divided into notoginseng group(n=10), gingko leaf group(n=10), rhodiola group(n=10) and high altitude control group(n=10) after fed in a hypobaric hypoxia chamber(simulated altitude of 5 000 m) for 3 month, while 10 rats fed at normal pressure and oxygen environment for 3 month were used as the plain control group. Rats in notoginseng group, gingko leaf group and rhodiola group were treated with notoginseng, gingko leaf tablets or rhodiola suspension through intragastric administration (200 mg/kg,twice a day, for 10 days). After the rats got intraperitoneal anesthesia with 10% urethane, 5 min pulmonary artery pressure curve were traced continuously while pulmonary artery pressure (PAP). Left and right ventricular systolic pressure (VSP) and ventricular diastolic pressure (VEDP), the hemodynamic parameters were detected through a multi-channel physiological recorder. Serum tumor necrosis factor-α(TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), superoxide dismutase (SOD) and malondialdehyde (MDA) were measured. Right ventricular systolic pressure (RVSP), right ventricular end-diastolic pressure (RVEDP), mean pulmonary artery pressure (mPAP), left vent-ricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP),IL-6,and IL-10 were higher in notoginseng group, gingko leafgroup, rhodiola group and high altitude control group than those in plain control group(P＜0.05 or P＜0.01). The contents of MDA and TNF-α were higher while the level of SOD was lower in rhodiola group and high altitude control group than those in plain control group(P＜0.01). The contents of MDA and TNF-α were lower while the level of SOD was higher in notoginseng group, gingko leaf group and rhodiola group than those in high altitude control group(P＜0.01). The levels of RV,RVHI,RVSP,RVEDP,LVSP,LVEDP,IL-10 and TNF-α were statistically changed in notoginseng group than those in gingko leaf group and rhodiola group(P＜0.05orP＜0.01). Notoginseng, gingkoleaf and rhodiola can enhance antioxidant capacity of body and improve ventricular functions and Notoginseng, gingko leaf and rhodiola can effectively enhance the functions of ventricular and hypoxia tolerance and inhibit the expressions of inflammatory factors in rats during the hypoxia deacclimatization.

The improvement of oxidative stress by two proprietary herbal medicines in type 2 diabetes

ObjectiveTo evaluate the impact to oxidative stress, atherosclerosis and macrovascular disease by two proprietary herbal medicines including Ginkgo Leaf Tablets and Liuwei Dihuang Pills in type 2 diabetes. MethodsThe recruited 140 type 2 diabetes were randomly divided into the treatment group and control group which were both received basic diabetic management including anti-hyperglycemia, anti-hypertension, life style adjustment and health education etc. Additionally, the treatment group was given both Ginkgo Leaf Tablets and Liuwei Dihuang Pills while the control group was given placebos of Ginkgo Leaf Tablets and Liuwei Dihuang Pills. The relative clinical indexes about macrovascular events occurrence, atherosclerosis degree(IMT levels), oxidative stress in vivo(plasma carboxymethyl lysine(CML) and 8-isoprostane(8-IsoP) levels), plasma glucose, plasma lipid, blood pressure, other drugs usage situations and so on of two groups before and after consecutive 36-month treatment were accurately collected and statistically analyzed. ResultsThere were no significant differences of cardiovascular disease, cerebrovascular disease, IMT levels, plasma CML and 8-IsoP levels between the two groups before treatment. After 36-month treatment, the plasma CML and 8-IsoP levels of treatment group were both significantly lower than control group (CML: 312.4 ± 90.4 ng/ml versus 463.5 ± 97.2 ng/ml, P < 0.0001; 8-IsoP: 23.7 ± 9.5 pg/ml versus 62.6 ± 16.1 pg/ml, P < 0.0001) although this improvement was not shared with IMT and macrovascular events. ConclusionGinkgo Leaf Tablets and Liuwei Dihuang Pills are beneficial to oxidative stress which plays important role in diabetic atherosclerosis and macrovascular complications. The preventive and therapeutic values of herbal medicines will be proved in further diabetic complication researches.

Effects of Ginkgo leaf tablets on the pharmacokinetics of losartan and its metabolite EXP3174 in rats and its mechanism

Context: Ginkgo leaf tablets (GLTs) and losartan are often simultaneously used for the treatment of hypertension in Chinese clinics. However, the herb–drug interaction between GLT and losartan is still unknown.Objective: This study investigates the effects of GLT on the pharmacokinetics of losartan and its metabolite EXP3174 in rats and its potential mechanism.Materials and methods: The pharmacokinetic profiles of losartan and EXP3174 of orally administered losartan (10 mg/kg) with or without GLT pretreatment (80 mg/kg/day for 10 days) in Sprague–Dawley rats were determined. In vitro, the effects of GLT on the metabolic stability of losartan were investigated with rat liver microsomes.Results: The Cmax (1.22 ± 0.25 vs 1.85 ± 0.37 μg/mL) and the AUC(0–t) (6.99 ± 1.05 vs 11.94 ± 1.79 mg·h/L) of losartan increased significantly (p < 0.05) with GLT pretreatment, while the Cmax (1.05 ± 0.19 vs 0.72 ± 0.12 μg/mL) of EXP3174 decreased significantly (p < 0.05) compared to the control. The t1/2 of losartan was prolonged significantly from 3.94 ± 0.62 to 4.75 ± 0.52 h (p < 0.05). The metabolic stability of losartan was increased from 37.4 min to 59.6 min with GLT pretreatment.Discussion and conclusions: The results indicate that GLT might increase the plasma concentration of losartan and decrease the concentration of EXP3174 through inhibiting the metabolism of losartan.

Application of quality by design in granulation process for ginkgo leaf tablet (Ⅱ)： identification of critical quality attributes

Quality by design (QbD) highlights the concept of "begin with the end", which means to thoroughly understand the target product quality first, and then guide pharmaceutical process development and quality control throughout the whole manufacturing process. In this paper, the Ginkgo biloba granules intermediates were taken as the research object, and the requirements of the tensile strength of tablets were treated as the goals to establish the methods for identification of granules' critical quality attributes (CQAs) and establishment of CQAs' limits. Firstly, the orthogonal partial least square (OPLS) model was adopted to build the relationship between the micromeritic properties of 29 batches of granules and the tensile strength of ginkgo leaf tablets, and thereby the potential critical quality attributes (pCQAs) were screened by variable importance in the projection (VIP) indexes. Then, a series of OPLS models were rebuilt by reducing pCQAs variables one by one in view of the rule of VIP values from low to high in sequence. The model performance results demonstrated that calibration and predictive performance of the model had no decreasing trend after variables reduction. In consideration of the results from variables selection as well as the collinearity test and testability of the pCQAs, the median particle size (D₅₀) and the bulk density (Da) were identified as critical quality attributes (CQAs). The design space of CQAs was developed based on a multiple linear regression model established between the CQAs (D₅₀ and Da) and the tensile strength. The control constraints of the CQAs were determined as 170 μm< D₅₀<500 μm and 0.30 g•cm⁻³<Da<0.44 g•cm⁻³ according to the design space, which provided a basis for controlling and optimizing the wet granulation process of the ginkgo leaf tablet..

Application of quality by design in granulation process for ginkgo leaf tablet (Ⅰ)： comprehensive characterization of granule properties

In this paper, the granules intermediate prepared from the wet granulation process of ginkgo leaf tablet were taken as the research object, and then the stackability, homogeneity, flowability, compressibility and stability of granules were characterized by using micromeritics evaluation method. The physical fingerprint of granules were constructed by 16 indexes including bulk density, tapped density, span, width, relative homogeneity index, aspect ratio, Hausner ratio, angle of repose, granule flow time, inter-particle porosity, Carr index, specific surface area, pore volume, pore size distribution, loss on drying and hygroscopicity. Furthermore, compressibility parameters (i.e. index of parameter, index of parametric profile and index of good compression) were employed to analyze the compressibility characteristics of the granules. Two principal components (first principal component representing dimension parameter and second principal component representing morphology parameter), could be extracted from the physical fingerprint by the principal component analysis (PCA). The granules' physical fingerprint is of great importance to evaluate the batch-to-batch quality consistency of Ginkgo biloba granules and analyze the potential impacts of granules' quality attributes on product quality, which can provide guidance for the granules' quality control and process development..

Application of quality by design in granulation process for Ginkgo leaf tablet (Ⅲ)： process control strategy based on design space

In this paper, under the guidance of quality by design (QbD) concept, the control strategy of the high shear wet granulation process of the ginkgo leaf tablet based on the design space was established to improve the process controllability and product quality consistency. The median granule size (D50) and bulk density (Da) of granules were identified as critical quality attributes (CQAs) and potential critical process parameters (pCPPs) were determined by the failure modes and effect analysis (FMEA). The Plackeet-Burmann experimental design was used to screen pCPPs and the results demonstrated that the binder amount, the wet massing time and the wet mixing impeller speed were critical process parameters (CPPs). The design space of the high shear wet granulation process was developed within pCPPs range based on the Box-Behnken design and quadratic polynomial regression models. ANOVA analysis showed that the P-values of model were less than 0.05 and the values of lack of fit test were more than 0.1, indicating that the relationship between CQAs and CPPs could be well described by the mathematical models. D₅₀ could be controlled within 170 to 500 μm, and the bulk density could be controlled within 0.30 to 0.44 g•cm⁻³ by using any CPPs combination within the scope of design space. Besides, granules produced by process parameters within the design space region could also meet the requirement of tensile strength of the ginkgo leaf tablet..

Application of quality by design in granulation process for ginkgo leaf tablet (Ⅳ)： influence and control of raw materials' quality variation

Raw materials' quality variation could affect the quality consistency of product and the clinical efficacy. In this paper, the high shear wet granulation (HSWG) process of the ginkgo leaf tablet was taken as the research object. Ginkgo biloba extracts and excipients microcrystalline cellulose collected from various sources and batches were used to simulate raw materials' quality variation. Real-time torque was recorded to analyze the viscosity of the wetting mass, and then by combining with physical fingerprint, the impact of physical quality variation of powders on granule properties could be investigated. Based on regime map thesis, whether the granules' nucleation mode was in mechanical dispersion regime was determined by calculating dimensionless parameters, which would lead to the unstable output in considerations of granule yield ratio and particle size distribution (PSD) curve. The orthogonal partial least square (OPLS) model was adopted to build the relationship between the micromeritic properties and the mediangranule size (D50) of Ginkgo biloba granules and then the critical material attributes (CMAs) were screened by variable importance in the projection (VIP) indexes. The results demonstrated that the properties of powders including hygroscopicity, angle of repose, Hausner ratio, Carr index, D10 and loss on drying affected the granule size. Besides, Ginkgo biloba granules were compressed into tablets. In view of tensile strength analysis, the raw materials' quality variation did not result in decrease of tensile strength of the ginkgo leaf tablets. The design space of critical quality attributes (CQAs) and the process design space which could cope with raw materials' quality variation were proved to be robust..

The Role of Liuwei Dihuang Pills and Ginkgo Leaf Tablets in Treating Diabetic Complications.

Objective. To observe the clinical prophylactic and therapeutic efficacy of Liuwei Dihuang Pills and Ginkgo Leaf Tablets for type 2 diabetic vascular complications. Methods. It was a randomized, double-blind and placebo-controlled clinical trial. 140 outpatients with type 2 diabetes were recruited and randomly divided into the treatment group and control group. The two groups were given basic therapy (management of blood sugar, blood pressure, etc.). Additionally, the treatment group was given Liuwei Dihuang Pills and Ginkgo Leaf Tablets, while the control group was given Liuwei Dihuang Pills and Ginkgo Leaf Tablets placebos. All subjects were followed up for consecutive 36 months and observed monthly. The clinical data as urinary microalbumin to urinary creatinine ratio (Umalb/cr), carotid intima-media thickness (IMT), diabetic nephropathy (DN) and diabetic retinopathy (DR) prevalence, cardiovascular and cerebrovascular events, blood glucose, and blood pressure were collected and analyzed statistically. Results. After 36-month treatment, the Umalb/cr level and DN and DR prevalence in treatment group were all significantly lower than control group (P < 0.05). However, the IMT level and the incidence of cardiovascular and cerebrovascular events were not significantly different between the two groups (P > 0.05). Conclusions. Liuwei Dihuang Pills and Ginkgo Leaf Tablets are beneficial to diabetic microvascular complications, while the efficacy to diabetic macrovascular complications needs more observations.

Effect of Ginkgo Leaf Tablets on the Pharmacokinetics of Amlodipine in Rats.

Ginkgo leaf tablet (GLT) is an effective traditional Chinese multi-herbal formula, which is often combined with amlodipine for treating senile hypertension in clinic. The aim of this study was to study the pharmacokinetics of amlodipine after oral administration of amlodipine and GLT and to investigate the potential for pharmacokinetic herb-drug interactions between GLT and amlodipine in rats. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) analytical method was developed for quantification of amlodipine in rat plasma. The accuracy, precision, linearity, selectivity and recovery were all within an acceptable range. Male Sprague-Dawley rats were randomly assigned to two groups: amlodipine group and amlodipine+GLT group. Plasma concentrations of amlodipine were determined at the designated time points after oral administration by using the developed LC-MS/MS method, and the main pharmacokinetic parameters were calculated and compared. As ginkgolides A, ginkgolides B, bilobalide, quercetin and kaempferol were the main components of GLT, the effects of these ingredients in GLT on metabolism of amlodipine were further investigated in rat liver microsomes. The pharmacokinetic parameters, maximum plasma concentration (C max), time to reach C max (T max), area under the concentration-time curve (AUC), area under the first moment plasma concentration-time curve (AUMC) and elimination half-life (t 1/2), of amlodipine were significantly increased in amlodipine+GLT group, which suggested that GLT may influence the pharmacokinetic behavior after oral co-administration with amlodipine. Amlodipine is metabolized by cytochrome P450 (CYP) 3A4, so it was speculated that GLT may change the pharmacokinetic parameters of amlodipine through modulating the metabolism of CYP3A4 enzymes. When ginkgolides B, bilobalide, or quercetin and amlodipine were co-incubated in the rat liver microsomes, the metabolic rate of amlodipine was prolonged to 533.1, 216.1 and 407.6min, respectively, from 73.7min. These results suggested that these components in GLT inhibit the metabolism of amlodipine. So it can be speculated that the herb-drug interactions between GLT and amlodipine resulted from inhibiting the metabolism of amlodipine by GLT when they were co-administered.

Effects of Ginkgo biloba extract in improving episodic memory of patients with mild cognitive impairment: a randomized controlled trial

Mild cognitive impairment is a transitional stage between normal aging and dementia. It is important in terms of recognizing memory loss in older people as well as identifying a group of individuals at high risk of developing dementia and who may benefit from preventive strategies. Ginkgo biloba extract has been shown to possess polyvalent properties, such as anti-oxidation, anti-apoptosis and anti-inflammation. Ginkgo biloba extract appears to have a neuroprotective effect against neurodegenerative diseases. To observe the efficacy of Ginkgo biloba leaf tablet in improving episodic memory of mild cognitive impairment. This is a multicenter, randomized, controlled trial. The authors enrolled generally healthy, ambulatory or ambulatory-aided amnestic subjects with MCI, 60 to 85 years old, who expressed a memory complaint from Huadong Hospital, seven Community Health Centers in Shanghai, and Shanghai First Welfare Institution. A total of 120 MCI patients were randomly assigned to the Ginkgo biloba leaf tablet group (treatment group, 60 cases) and control group (60 cases). The patients in the treatment group took Ginkgo biloba leaf tablets 3 times a day, 19.2 mg each dose. The control group did not receive any intelligence-promoting or vasodilator reflex treatment except some health care. The patients were tested with nonsense picture recognition of the clinical memory scale and the logical memory test based on the Wechsler memory scale before and after treatment. After 6 months of treatment, the scores of the logical memory test and nonsense picture recognition were increased significantly in the treatment group (P<0.01, P<0.05), while the scores of the two tests from the control group had no statistically significant difference (P>0.05). After treatment, the positive rate of nonsense picture recognition was 55.17% in the treatment group, which was significantly higher than that of the control group at 32.73% (P<0.05). The efficacy rate of logical memory was 58.62% in the treatment group, also higher than 38.18% in the control group (P<0.05). Ginkgo biloba leaf tablet showed good efficacy in promoting episodic memory function in MCI patients.

Effect of aloe polysaccharide on caspase-3 expression following cerebral ischemia and reperfusion injury in rats

Stroke is a leading cause of cardiovascular morbidity, economic and social burden and mortality. Novel approaches are needed to address stroke prevention and treatment. The purpose of this study was to explore the effects of aloe polysaccharide on caspase-3 expression following cerebral ischemia reperfusion injury in rats. Male Wistar rats were randomly divided into 5 groups (16 rats in each group): aloe polysaccharide, ginkgo leaf tablet, nimodipine, model and sham surgery groups. The rats were administered the appropriate drug or normal saline for 7 days by gavage. A rat model of cerebral ischemia and reperfusion injury was established using the middle cerebral artery occlusion (MCAO) model. Caspase-3 protein and mRNA expression levels in the cerebral cortex were detected by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR), respectively. Results showed that caspase-3 protein and mRNA expression levels in the cerebral cortex in the aloe polysaccharide, ginkgo leaf tablet and nimodipine groups were significantly lower compared with the model group and were higher than the sham surgery group (P<0.05). No significant difference was observed in caspase-3 protein and mRNA expression among the aloe polysaccharide, the ginkgo leaf tablet and the nimodipine groups (P>0.05). In conclusion, aloe polysaccharide has a protective effect on cerebral ischemia that may be due to the inhibition of neuronal cell apoptosis.

Voltammetric behavior and the determination of quercetin at a flowerlike Co3O4 nanoparticles modified glassy carbon electrode

Flowerlike Co3O4 nanoparticles were used as a modifier on the glassy carbon electrode to fabricate a quercetin (Qu) sensor. The morphology and crystallinity of the prepared Co3O4 material were investigated by scanning electron microscopy and X-ray diffraction. Electrochemical behavior of Qu at the sensor was studied by cyclic voltammetry and semi-derivative voltammetry. Results suggested that the modified electrode exhibited a strong electrocatalytic activity toward the redox of Qu. The electron transfer coefficient (α), the number of electron transfer (n), and the diffusion coefficient (D) of Qu at the sensor were calculated. Under the optimum conditions, the catalytic peak currents of Qu were linearly dependent on the concentrations of Qu in the range from 5.0 × 10−7 to 3.3 × 10−4 M, with a detection limit of 1.0 × 10−7 M. This proposed method was successfully applied to determine the quercetin concentration in Ginkgo leaf tablet and human urine samples.

Clinical study on treatment of liver fibrosis of chronic hepatitis B patients with Ginkgo leaf

To study the anti-liver fibrosis effect of Ginkgo leaf in patients with chronic hepatitis B.Methods: Eighty-six patients with chronic hepatitis B were randomly divided into two groups with similar general condition. The 42 patients in the treated group were treated with Ginkgo leaf tablet (GLT), and the 44 patients in the control group were treated with Yiganling tablet. The treatment was conducted for 3 successive months in both groups. Changes in the histo-pathology of liver, serum levels of platelet activating factor (PAF), hyaluronic acid (HA), collagen type IV (C-IV), laminin (LN) and pro-collagen peptide type III (PC III) were observed before and after treatment. The markedly effective rate and the total effective rate in the treated group were 45.1% and 76.2% respectively, while in the control group the corresponding rates were 18. 2% and 43. 2%. Comparison between the two groups showed significant differenceP<0.01). Serum levels of PAF, HA, C-IV, LN and PC III were lowered significantly in the treated group after treatment. Compared with the corresponding parameters in the control group after treatment, the differences were all significant (P<0.01 orP<0.05). The pathological examination of liver showed improvement in both groups, the inflammation grade lowered in 10 patients (55. 6%) of the treated group and in 5 patients (35. 7%) of the control group, insignificant difference was shown between them. But in comparing the fibrosis staging lowering patients between the two groups, 12 patients (66. 7%) vs 3 patients (21.4%), the difference was significantP<0.05). Moreover, there were 4 patients in the control group with their fibrosis aggravated, while in the treated group, none was aggravatedP<0.05). Ginkgo leaf tablet has some liver protective and anti-liver fibrosis benefits.