Ginkgo biloba extract (EGb761) inhibits mitochondria-dependent caspase pathway and prevents apoptosis in hypoxia-reoxygenated cardiomyocytes

Abstract

BackgroundEGb761 is a standard extract from the leaves of Ginkgo biloba (Yinxing) containing ginkgo-flavone glycosides and terpenoid. The flavonoid components of EGb761 scavenge free radicals and protect myocardia from ischemia-reperfusion injury. The present study aims to determine the effects of the active compounds of EGb761 on mitochondria-dependent caspase pathway.MethodsCardiomyocytes were exposed to 24 hours of hypoxia and four hours of reoxygenation, and pretreated with EGb761, bilobalide and quertcetin. By using immunoblot, immunofluorescent, biochemical and flow cytometry techniques, we compared the effects of EGb761 and its representative constituents including quercetin and bilobalides on regulating mitochondria-dependent caspases signal pathway and apoptotic cell death in the hypoxia-reoxygenated cardiomyocytes.ResultsPretreatment with EGb761 significantly inhibited the release of cytochrome c from mitochondria, the expression of caspase-3, cleavage activities of caspases and attenuated apoptotic cell death. The effects of quercetin on the release of cytochrome c, the cleavage activities of caspases and cell death were similar to those of EGb761 but better than those of bilobalide.ConclusionThe antioxidant constituents of EGb761 such as quercetin contribute to the cardioprotective effects of EGb761 and inhibit the mitochondria-dependent caspase pathway. It is possible that the mitochondria-dependent caspase pathway may be one of the molecular targets of EGb761 against myocardial ischemia-reperfusion injury.

Role of polyphenols in cell death control

“…by activating the nuclear factor erythroid-derived 2-related factor 2 (Nrf2) transcription factor pathway. 120,121 Resveratrol as well as quercetin, catechins, and procyanidins have been demonstrated to counteract oxidative stress-induced apoptosis by increasing the level of mitochondrial antioxidant enzymes and modulating specific signalling pathways and kinase activities, [122][123][124][125][126][127][128][129][130][131] which result in a complex regulation of the balance between pro-and anti-apoptotic Bcl-2 family members. [132][133][134][135][136] These activities might be due to the capability of polyphenols to accumulate in mitochondria.…”

Protective Effects of Ginkgo Biloba Dropping Pills Against Liver Ischemia/reperfusion Injury in Mice

“…A standardized Ginkgo biloba extract 761 (EGb 761) has been used as strong antioxidative and neuroprotective agent to treat neurodegenerative diseases [21]. Furthermore, several researches have indicated that EGb 761 protects against renal, myocardial, and cerebral ischemiareperfusion injury [22][23][24][25], and improves hepatic DNA damage and liver microcirculation after warm ischemia [26,27]. Ginkgo biloba Dropping Pill (GBDP) is a unique Ginkgo biloba leaf extract preparation produced in China for treating angina pectoris and cerebral infarction caused by blood stasis.…”

Antioxidant Activity and Antibacterial Effects on Clinical IsolatedStreptococcus suisandStaphylococcus intermediusof Extracts from Several Parts ofCladogynos orientalisand Their Phytochemical Screenings

“…Previous report suggested that the extract from the whole plant of C. orientalis promoted antidengue virus effect using MTT assay [ 2 ]. The leaf extract also promoted effective inhibition of human hepatocarcinoma (HepG2) [ 3 ]. It was previously reported that terpenoid compounds including ent-halimane diterpenes; chettaphanin I and chettaphanin II, sesquiterpenes; 8-hydroxy-alpha-guaiene, spathulenol, cyperenoic acid, and triterpenes; and taraxerol and acetoxyaleuritolate were the major components in C. orientalis [ 4 – 6 ].…”

“…Some unusual aromatic diglycosides including 4′′-O-galloyl-violutoside and 4′′-O-galloyl-benzyl-O- α -L-rhamnopyranosyl-(1→6)- β -D-glucopyranoside and some flavonoids such as isovitexin and apigenin glycosides were found in the aerial part of this plant [ 7 ]. Moreover, the leaves were also reported to contain some phenolics and flavonoids including chlorogenic acid, epicatechin, and quercetin [ 3 ]. Despite reports suggesting some biological activities of C. orientalis extract, the ethnomedical use of this plant as tonic and agent to treat flatulence and stomachache is yet to be investigated.…”