银杏叶提取物对高脂血症调脂机制的新探

目的 :通过观察银杏叶提取物对高脂血症病人调脂过程中肠道菌群的变化来探讨其调脂机制。方法 :对于 2 2名高脂血症患者给予银杏叶提取物 9片 / d,治疗 4w,检测其治疗前后空腹血脂变化 ,及高脂血症组治疗前与正常人肠道菌群变化 ,和高脂血症组治疗前后肠道菌群变化。结果 :(1)高脂血症患者经银杏叶提取物治疗后 TC、TG、L DL-C较治疗前均明显降低 (P<0 .0 5)。 (2 )高脂血症患者银杏叶提取物治疗前较正常人肠道菌群变化显著 (P<0 .0 1)。高脂血症组银杏叶治疗后较治疗前肠道菌群变化显著 (P<0 .0 1)。结论 :(1)银杏叶提取物降脂有显著疗效。 (2 )脂质代谢紊乱时肠道菌群较正常人明显变化 (P<0 .0 1) ,尤其双歧杆菌、乳杆菌等明显减少 ,而治疗后肠道菌群得到调整 ,说明银杏叶可能通过扶植肠道有益菌生长繁殖 ,如双歧杆菌、乳杆菌等对脂质代谢发挥作用 ,达到其调脂目的     

银杏叶提取物对糖尿病大鼠脂质代谢及肠道正常菌群的影响

目的:观察银杏叶提取物对糖尿病大鼠脂质代谢的影响,同时进一步探讨调脂机制.方法:选取糖尿病大鼠灌胃给予银杏叶提取物120 mg/(kg·d),共8周,检测其空腹血脂变化,及其肠道菌群变化.结果:(1)银杏叶提取物治疗后,治疗组较糖尿病对照组,总胆固醇、甘油三脂、低密度脂蛋白、胆固醇明显降低(P＜0.01);(2)糖尿病组肠道菌群较正常组明显变化(P＜0.01),尤其双歧杆菌、乳杆菌等明显减少,而治疗后肠道菌群得到调整.结论:银杏叶提取物可能通过扶植肠道菌群有益菌生长繁殖,对脂质代谢发挥作用,从而达到其调脂目的.     

紫草素在消化系统肿瘤中的抗癌机制研究进展

消化系统肿瘤是威胁我国居民生命健康的重要杀手,其发病率和死亡率均占全部肿瘤的50%左右,研发高效安全的抗肿瘤药物是治疗消化系统肿瘤的基础。植物提取物是抗肿瘤药物的重要来源,紫草素(Shikonin)是一种存在于紫草科植物根茎中的药物成分,它对消化系统肿瘤细胞具有显著的杀伤效果。本文通过检索最近10年紫草素在消化系统肿瘤中发挥抗癌作用的相关文献,对紫草素及其衍生物在消化系统肿瘤中的抗癌机制进行系统归纳整理,并分析了今后紫草素应用于临床治疗消化系统肿瘤的研究方向,为进一步探索紫草素在消化系统肿瘤中的抗癌机制研究和新药研发提供理论依据。     

三七总皂甙和银杏叶提取物预防急性氧中毒的实验研究

目的:研究三七总皂甙和银杏叶提取物对急性氧中毒的预防作用及其可能机制.方法:分别给小鼠连续腹腔注射三七总皂甙和银杏叶提取物5 d后,在500kPa高压氧中暴露60 min,观察惊厥潜伏期、惊厥次数、惊厥间隔时间等指标;另外测定高压氧暴露15 min后脑组织中活性氧单位、脂质过氧化物、一氧化氮、谷胱甘肽的含量和过氧化氢酶、谷胱甘肽过氧化物酶、单胺氧化酶的活性.结果:三七总皂甙和银杏叶提取物可以明显延长氧惊厥潜伏期和惊厥间隔时间,减少惊厥次数;降低高压氧暴露后脑组织中脂质过氧化物、一氧化氮的含量,使活性氧单位、谷胱甘肽含量和谷胱甘肽过氧化物酶活性保持在较高的水平;对过氧化氢酶和单胺氧化酶活性的影响则不显著.结论:三七总皂甙和银杏叶提取物可以有效预防急性氧中毒,其机制可能与它们的抗氧化活性有关.     

植物次生代谢产物及其衍生物的抗肿瘤成药研究进展

面对严重威胁健康的肿瘤,人类从未间断过抗肿瘤药物的研发。纵观历史,从非选择性的化疗药物,到特异性阻断驱动致癌基因的靶向药物,直到今天以患者为中心的个体化肿瘤治疗,抗癌药物迅猛发展,成为提高肿瘤患者生存率的重要治疗手段。然而,由于大多数抗癌药物存在难以克服的短期耐药及毒副作用等问题,严重影响临床治疗效果。近年,筛选植物来源的天然提取物及其次生代谢产物的抗癌作用,倍受关注并取得令人瞩目的进展,包括临床广泛应用的紫杉醇、长春新碱、依托泊苷及喜树碱等。总结植物的抗肿瘤活性成分、筛选方法、潜在作用机制及临床应用等国内外研究现状,旨在为植物来源的抗肿瘤药物的深入研发提供参考。     

香菇提取物的生物作用概述

针对香菇提取物具有抗病毒、抗细菌、抗肿瘤以及调节免疫功能等特点,介绍了香菇提取物的多种生物作用和作用机制,最后指出香菇提取物在临床治疗和预防中的广阔应用前景。     

银杏叶提取物及其活性成分改善认知功能作用的研究进展

银杏叶提取物是目前临床上最常用的中药提取物之一,具有广泛的药理作用,其主要的活性成分包括银杏黄酮、银杏内酯以及白果内酯。早年研究发现,银杏叶提取物具有保护中枢神经系统的作用并且能显著改善疾病所导致的认知功能障碍,包括阿尔茨海默症、血管性痴呆以及糖尿病脑病。本文就银杏叶提取物及其活性成分通过对信号通路的影响、对凋亡相关蛋白的影响、抗氧化作用来改善认知功能的可能分子机制及其体外对神经细胞的保护作用进行综述。     

银杏叶黄酮含量对银杏叶提取物大孔树脂纯化工艺条件的影响研究

为考察银杏叶中黄酮含量对银杏叶提取物质量、得率及黄酮提取率的影响,为银杏叶提取物的生产提供原料标准和对应的工艺参数,本文选取黄酮含量分别为1.0%、0.8%和0.6%的三批银杏叶,在保证提取物质量满足中国药典要求的前提下,探究银杏叶质量的变化对提取物大孔树脂纯化工艺条件的影响。采用统计回归方法分别建立了银杏叶提取物的黄酮含量、提取物得率及黄酮提取率与纯化乙醇浓度和体积之间的关系。研究发现银杏叶提取物中黄酮含量与乙醇浓度及洗脱液体积正相关;提取物得率与洗脱液体积负相关、与乙醇浓度的关系随银杏叶中黄酮含量而变化;低黄酮含量银杏叶的提取物质量对工艺参数最为敏感;提取物中内酯含量与银杏叶中黄酮含量呈正相关关系并与提取物中黄酮含量、洗脱液体积呈负相关关系。为保证提取物质量、工艺条件和得率的稳定,建议通过不同质量原料混合的方式使银杏叶中黄酮含量维持在1%,采用2倍量15%乙醇进行洗脱,可获得黄酮含量大于24%、内酯含量6%,得率2.6%、黄酮提取率大于66%的银杏叶提取物。     

天然提取物诱导人HepG2 细胞凋亡的研究进展

细胞凋亡是机体维持内环境稳定,更好的适应生存环境采取的一种死亡过程。细胞凋亡异常与肿瘤的发生、发展存在密切的关系。细胞凋亡的信号途径主要有死亡受体介导的外源性通路、线粒体介导内源性通路、内质网信号通路及MAPK信号通路。通过作用于凋亡信号通路上一些关键基因,诱导肿瘤细胞凋亡被认为是临床抗肿瘤治疗最有成效的治疗方法之一。研究已证实多种天然提取物作用于凋亡信号途径中一些重要因子可诱导细胞凋亡,并取得较好的抑制肿瘤增殖的效果。本文是关于细胞凋亡机制及各种天然提取物作用于凋亡通路上主要基因进行抗肿瘤治疗研究进展的综述。     

银杏叶聚戊烯醇抗肿瘤的生物活性研究

目的 :从银杏叶中分离聚戊烯醇新的有效部位 ,研究聚戊烯醇抗肿瘤的药效。方法 :通过提取、分离、精制 75 %以上银杏叶聚戊烯醇 ,以氟脲嘧啶 (5 Fu)为对照 ,选择肝癌 (Heps)实体型、肉瘤 (S180 )、艾氏癌 (EC)实体型等瘤谱 ,用不同剂量的聚戊烯醇进行小鼠移植性抗肿瘤药效实验。结果 :银杏叶聚戊烯醇对Heps、S180 和EC等移植性瘤谱的最高抑瘤率分别为 4 9 2 9%、6 0 89%和 5 2 4 7% (p <0 .0 0 5 )。结论 :银杏叶聚戊烯醇具有明显的抑制肿瘤的生物活性。     

Alzheimer's disease, the nematode Caenorhabditis elegans, and ginkgo biloba leaf extract

Alzheimer's disease (AD) is affecting larger and larger proportions of our population as lifespan increases. Thus, the means to prevent or reduce the rate of this disorder is a high priority for medical research. A standardized extract of Ginkgo biloba leaves EGb 761 is a popular dietary supplement taken by the general public to enhance mental focus and by the elderly to delay onset of age-related loss of cognitive function. EGb 761 has been used for treatment of certain cerebral dysfunctions and dementias associated with aging and AD. Substantial evidence indicates that EGb 761 has neuroprotective effects. But, mechanisms of action of the components of the extract are, unfortunately, poorly understood. Research in my laboratory focuses on understanding mechanisms of action of the components of the herbal extract EGb 761 in protection against Alzheimer's disease. We have demonstrated that EGb 761 inhibited amyloid beta aggregation in vitro and attenuates reactive oxidative species (ROS) in a model organism - the round worm Caenorhabditis elegans. Furthermore, EGb 761 eased its toxicity in the transgenic C. elegans. We also found that only a certain size of the amyloid beta aggregates is toxic to the worms. These findings suggest that EGb 761 has a clear therapeutic potential for prevention and/or treatment of AD. A better understanding of the mechanisms of neuroprotection by EGb 761 will be important for designing therapeutic strategies, for basic understanding of the underlying neurodegenerative processes, and for a better understanding of the effectiveness and complexity of this herbal medicine.     

EGb761 Provides a Protective Effect against Aβ1-42 Oligomer-Induced Cell Damage and Blood-Brain Barrier Disruption in an In Vitro bEnd.3 Endothelial Model

Alzheimer’s disease (AD) is the most common form of senile dementia which is characterized by abnormal amyloid beta (Aβ) accumulation and deposition in brain parenchyma and cerebral capillaries, and leads to blood-brain barrier (BBB) disruption. Despite great progress in understanding the etiology of AD, the underlying pathogenic mechanism of BBB damage is still unclear, and no effective treatment has been devised. The standard Ginkgo biloba extract EGb761 has been widely used as a potential cognitive enhancer for the treatment of AD. However, the cellular mechanism underlying the effect remain to be clarified. In this study, we employed an immortalized endothelial cell line (bEnd.3) and incubation of Aβ_1–42 oligomer, to mimic a monolayer BBB model under conditions found in the AD brain. We investigated the effect of EGb761 on BBB and found that Aβ_1–42 oligomer-induced cell injury, apoptosis, and generation of intracellular reactive oxygen species (ROS), were attenuated by treatment with EGb761. Moreover, treatment of the cells with EGb761 decreased BBB permeability and increased tight junction scaffold protein levels including ZO-1, Claudin-5 and Occludin. We also found that the Aβ_1–42 oligomer-induced upregulation of the receptor for advanced glycation end-products (RAGE), which mediates Aβ cytotoxicity and plays an essential role in AD progression, was significantly decreased by treatment with EGb761. To our knowledge, we provide the first direct in vitro evidence of an effect of EGb761 on the brain endothelium exposed to Aβ_1–42 oligomer, and on the expression of tight junction (TJ) scaffold proteins and RAGE. Our results provide a new insight into a possible mechanism of action of EGb761. This study provides a rational basis for the therapeutic application of EGb761 in the treatment of AD.     

Inhibitory effects of EGb761 on the expression of matrix metalloproteinases (MMPs) and cartilage matrix destruction

Cytokines such as tumor necrosis factor alpha (TNF-α)-induced expression of matrix metalloproteinase (MMP) play a pivotal role in the destruction of articular cartilage in patients who are suffering from osteoarthritis (OA). Collagen type II, the basis for articular cartilage, can be degraded by MMP-1, MMP-3, and 13. EGb761, the standardized extract of Ginkgo biloba produced by Dr. Willar Schwabe Pharmaceuticals, has shown its anti-inflammatory capacity. This study aimed to determine a mechanism whereby EGb761 may inhibit cartilage degradation. Our results indicated that pretreatment with EGb761 abolishes MMP-1, MMP-3, and MMP-13 gene expression and protein expression induced by TNF-α in human chondrocyte monolayer. In addition, the reduction of the tissue inhibitor of metalloproteinase-1(TIMP-1) and metalloproteinase-2 gene expression induced by TNF-α was rescued by pretreatment with EGb761. Importantly, TNF-α-induced degradation of collagen type II was ameliorated by EGb761 in a dose-dependent manner. Mechanistically, our results indicated that EGb761 treatment attenuated TNF-α-induced NF-κB activation. These actions of EGb761 suggest a mechanism by which EGb761 may act to prevent cartilage breakdown in arthritis.     

Reduction of rise in blood pressure and cortisol release during stress by Ginkgo biloba extract (EGb 761) in healthy volunteers.

The standardized extract of Ginkgo biloba (EGb 761) was found not only to improve memory and aging associated cognitive deficits but also to exert beneficial effects on mood. An antistress action of the extract has been suggested but not directly proven. The present study was aimed to evaluate the effects of EGb 761 on salivary cortisol and blood pressure responses during stress in healthy young volunteers (n = 70) in a double blind placebo controlled design. A stress model involving a combination of static exercise (handgrip) and mental stimuli was used. Single treatment with EGb 761 (120 mg) reduced stress-induced rise in blood pressure without affecting the heart rate. Salivary cortisol responses showed differences with respect to the gender and the time of day of the stress exposure, with the activation only in male subjects in the afternoon. This activation was absent if they were treated with EGb 761. The performance in a short memory test with higher scores achieved by women remained unaffected by EGb 761 treatment. Thus, this study provides evidence that EGb 761 has an inhibitory action on blood pressure and it may influence cortisol release in response to some stress stimuli.     

Ginkgo biloba extract (Egb 761) inhibits beta-amyloid production by lowering free cholesterol levels

Ginkgo biloba extract (EGb 761) can improve cognitive function in patients with Alzheimer's disease, but the molecular mechanisms underlying this effect remain undefined. Because free cholesterol may be involved in the production of β-amyloid precursor protein and amyloid β-peptide, key events in the development of Alzheimer's disease, we examined EGb 761 in relation to cholesterol and amyloidogenesis. In aging rats, EGb 761 treatment lowered circulating free cholesterol and inhibited the production of brain β-amyloid precursor protein and amyloid β-peptide. Exposure of PC12 cells to EGb 761 decreased the processing of β-amyloid precursor protein and abolished cholesterol-induced overproduction of this protein. Exposure of human NT2 cells to EGb 761 decreased free cholesterol influx and increased free cholesterol efflux. Our findings indicate that free circulating and intracellular cholesterol levels affect the processing of β-amyloid precursor protein and amyloidogenesis. Our findings also provide the first demonstration that EGb 761 can influence these mechanisms.     

Ginkgo biloba extract EGb 761 increases stress resistance and extends life span of Caenorhabditis elegans.

EGb 761, a standardized extract of Ginkgo biloba leaves, has been used in clinical trials for its beneficial effects on brain functions. In mammals, EGb 761 has been shown to enhance cognition, stress resistance, and longevity, but its molecular and cellular mechanisms are not known. In the present investigation, we used the model organism Caenorhabditis elegans to evaluate pharmacological effects of EGb 761 on aging. We tested the theory that EGb 761 augments the natural antioxidant system of C elegans, and thus increases stress resistance and longevity. We found that treatment of the wild-type worms with EGb 761 extended their median life span by 8%. Amongst several purified components of EGb 761, the flavonoid tamarixetin showed the most dramatic effect: it extended the median life span by 25%. Furthermore, EGb 761 increased the wild type's resistance to acute oxidative and thermal stress by 33% and 25%, respectively. Treatment of the prematurely aging mutant worms mev-1 with EGb 761 increased their resistance to acute oxidative and thermal stress by 33% and 11%, respectively. It appears that oxidative stress, a major determinant of life span, as well as other types of stress, can be successfully counteracted by the Ginlkgo biloba extract EGb 761.     

Effect of a short- and long-term treatment with Ginkgo biloba extract on amyloid precursor protein levels in a transgenic mouse model relevant to Alzheimer's disease

Several clinical trials have reported beneficial effects of the Ginkgo biloba extract EGb761 in the prevention and therapy of cognitive disorders including Alzheimer’s disease (AD). The aim of the present long-term feeding trial was to study the impact of dietary EGb761 on Amyloid precursor protein (APP) metabolism in mice transgenic for human APP (Tg2576). Tg2576 mice were fed diets with and without EGb761 (300 mg/kg diet) for 1 and 16 months, respectively. Long-term treatment (16 months) with EGb761 significantly lowered human APP protein levels by ∼50% as compared to controls in the cortex but not in the hippocampus. However, APP levels were not affected by EGb761 in young mice. Current data indicate that APP seems to be an important molecular target of EGb761 in relation to the duration of the Ginkgo biloba treatment and/or the age of the animals. Potential neuroprotective properties of EGb761 may be, at least partly, related to its APP lowering activity.     

Effect of the extract of Ginkgo biloba (EGb 761) on the circulating and cellular profiles of polyunsaturated fatty acids: correlation with the anti-oxidant properties of the extract

Ginkgo biloba extract (EGb 761) has beneficial effects on cognitive functions in aging patients, and on various pathologies, including cardiovascular diseases. Although the extract is known to have antioxidant properties and improve membrane fluidity, the cellular mechanisms underlying these effects have not been determined. Here, we examined the in vivo effects of EGb 761 on circulating and cellular lipids. EGb 761 treatment induced significant increases in the levels of circulating polyunsaturated fatty acids (PUFAs), and a decrease in the saturation index SI (saturated/polyunsaturated species). Plasma triglycerides and cholesterol were not affected, while phospholipids were slightly increased at the higher dose of EGb 761. EGb 761 treatment also induced a significant increase in the levels of PUFAs in erythrocyte membranes, especially for the eicosapentaenoic acid (EPA omega 3), and a decrease in the saturation index. Moreover, the response of erythrocytes to oxidative stress was improved in EGb 761-treated animals (H(2)O(2)-induced cell lysis decreased by 50%). Considering that PUFAs are known to improve membrane fluidity and response to oxidative damage, and are precursors of signaling molecules such as prostaglandins, the effects of EGb 761 on circulating and cellular PUFAs may explain some of the pharmacological properties of Ginkgo biloba.