The flavonoid fraction has antioxidant effects resulting from direct attenuation of reactive oxygen species by chelating pro-oxidant transitional metal ions, and also by promoting the expression of antioxidant proteins which in turn increases antioxidant metabolites such as glutathione. The chemical structure of flavonoids comprising of an aromatic ring and a double bond seem to react preferentially with hydroxyl radicals. The terpene lactones include the ginkgolides A, B, C, J and M, and bilobalide. These were found to reduce platelet activation and aggregation by antagonizing platelet activating factor. This gives EGb761 the potential to improve blood circulation. In addition, bilobalide, a sesquiterpene trilactone, was shown to reduce cerebral edema, cortical infarct volume and ischemic damage in patients following a stroke. EGb761 has also been shown to have various antiapoptotic properties and to inhibit amyloid-beta aggregation. Therefore, it has been used to improve cardiovascular and peripheral vascular insufficiency, to protect against neurological disorders such as ischemic injury and to treat cerebral disorders such as cognitive decline and memory impairment. Interestingly, in addition to its neurological and vascular protective effects, EGb761 has been reported to reduce hyperglycemia. Rapin et al. reported that EGb761 PF 05190457 increased glucose uptake and glycogen synthesis, and Tanaka et al. showed that the glucose-lowering effect of Ginkgo extracts was caused by the inhibition of alpha-amylase and glucosidase. The proliferation and migration of VSMCs are important contributors to neointimal formation after balloon injury. Apoptosis is also important in this process. Therefore, prior efforts to reduce the extent of restenosis have focused on various interventions that reduced the proliferation and migration of VSMCs or of increased their apoptosis. EGb761 has antioxidant, anti-inflammatory and anti-platelet aggregation effects. In our study, EGb761 also increased caspase-3 activity in VSMCs. It is known that EGb761 has antiapoptotic properties particularly in neuronal cells. However, EGb761 may also have different effects on cell survival under specific conditions such as target cells and the dosage used. Several studies showed that EGb761 had proapoptotic effects in high turnover state such as cancer. Thus, EGb761 could have proapoptotic effects on VSMCs in the development of atherosclerosis. It is well known that infiltration of inflammatory cells occur early after endothelial denudation and its inhibition is associated with a reduction in medial VSMC proliferation. These data suggest a central role of inflammatory cells in restenosis and provide PPDA insights as to how EGb761 might reduce neointimal growth in arteries after balloon injury.
LLL12 reduced tumor-associated angiogenic factors probably
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