Bilobalide and Neuroprotection

DeFeudis, F.V.

doi:10.1016/s1043-6618(02)00233-5

Cited by 132 publications

(93 citation statements)

References 14 publications

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“…Other groups reported neuroprotection by bilobalide in neuronal cell cultures where it counteracted apoptotic cell death induced by amyloid (Luo et al, 2002) and serum deprivation (Ahlemeyer et al, 1999). The neuroprotective properties of bilobalide have recently been reviewed (DeFeudis, 2002;Ahlemeyer and Krieglstein, 2003).…”

Section: Introductionmentioning

confidence: 99%

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Role of GABAergic antagonism in the neuroprotective effects of bilobalide

et al. 2007

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Bilobalide, a constituent of Ginkgo biloba, has neuroprotective properties. Its mechanism of action is unknown but it was recently found to block GABA A receptors. The goal of this study was to test the potential role of a GABAergic mechanism for the neuroprotective activity of bilobalide. In rat hippocampal slices exposed to NMDA, release of choline indicates breakdown of membrane phospholipids. NMDA-induced choline release was almost completely blocked in the presence of bilobalide (10 μM) and under low-chloride conditions. Bicuculline (100 μM), a competitive antagonist at GABA A receptors, reduced NMDA-induced choline release to a small extent (−23%). GABA (100 μM) partially antagonized the inhibitory action of bilobalide. Exposure of hippocampal slices to NMDA also caused edema formation as measured by increases of tissue water content. NMDA-induced edema formation was suppressed by bilobalide and by low-chloride conditions. Bicuculline exerted partial protection (by 30%) while GABA reduced bilobalide's effect by about one third.To investigate bilobalide's interaction with GABA A receptors directly, we measured binding of [ 35 S-TBPS] to rat cortical membranes. TBPS binding was competitively inhibited by bilobalide in the low micromolar range (IC 50 =3.7 μM). As a functional test, we determined 36 chloride flux in rat corticohippocampal synaptoneurosomes. GABA (100μM) significantly increased 36 chloride flux (+65 %), and this increase was blocked by bilobalide, but with low potency (IC 50 : 39 μM). We conclude that, while antagonism of GABA A receptors may contribute to bilobalide's neuroprotective effects, additional mechanisms must be postulated to fully explain bilobalide's actions.

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Section: Introductionmentioning

confidence: 99%

“…Bilobalide has been found to interfere with glutamatergic transmission, with mitochondrial function and apoptosis and it has genomic as well as proteomic effects (DeFeudis, 2002;Ahlemeyer and Krieglstein, 2003). The best available evidence, however, points to an interference with GABAergic neurotransmission.…”

Section: Introductionmentioning

confidence: 99%

Role of GABAergic antagonism in the neuroprotective effects of bilobalide

et al. 2007

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“…Rather, it supports that a more direct stimulus provided by EGb 761 may accelerate calcium influx. More production of ATP by EGb 761 due to functional enhancement of mitochondria may elicit calcium influx and stimulate insulin secretion, since the bilobalide component of Ginkgo was reported to increase the respiratory ratio of mitochondria and to elevate ATP levels (Defeudis, 2002). Measurement of intracellular ATP level and further study of mitochondrial function are required for determining the role of mitochondria and ATP in EGb 761-induced insulin secretion.…”

Section: Discussionmentioning

confidence: 99%

“…EGb 761 has also been shown to have various anti-apoptotic properties, which is derived by preserving the mitochondrial membrane integrity, up-regulating anti-apoptotic Bcl-2, down-regulating pro-apoptotic molecules like caspase-12 and inhibiting the activation of caspase-3 (Smith and Luo, 2004). As a result, EGb 761 has been used to improve cardiovascular and peripheral vascular insufficiency, to protect against neurological disorders like ischemic injury and to treat cerebral disorders such as cognitive decline and memory impairment (Defeudis, 2002). In addition to its neuro-and vascular protective effects, EGb 761 has been reported to reduce hyperglycemia.…”

Section: Introductionmentioning

confidence: 99%

Involvement of Ca2+, CaMK II and PKA in EGb 761-induced insulin secretion in INS-1 cells

Choi

Shin

Kim

et al. 2007

Journal of Ethnopharmacology

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“…In vitro and ex vivo studies indicate that bilobalide has multiple mechanisms of action that may be associated with neuroprotection, including its preservation of mitochondrial ATP synthesis, its inhibition of apoptotic damage induced by staurosporine or by serum-free medium, its suppression of hypoxia-induced membrane deterioration in the brain, and its action in increasing the expression of the mitochondrial DNA-encoded COX III subunit of cytochrome C oxidase and the ND1 subunit of NADH dehydrogenase. Because multiple modes of action may apply to bilobalide, it could be useful in developing therapy for disorders involving cerebral ischemia and neurodegeneration [235][236][237] .…”

Section: Herbsmentioning

confidence: 99%

Chinese Medicine and Biomodulation in Cancer Patients—Part Two

Sagar

Wong

2008

Current Oncology

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Traditional Chinese Medicine (TCM) is a whole system containing therapeutic interventions that individually induce biomodulation at the physiologic, chemical, and molecular levels. The theory of TCM proposes a synergy between specific interventions selected as part of a care plan based on TCM diagnostic theory. Combining TCM with the modern practice of oncology seems, in conjunction with biomedical interventions (surgery, radiotherapy, chemotherapy, and pharmaceuticals), to have potential advantages through the synergy of biomodulation. Biomodulation approaches are broadly categorized as modification of tumour response and reduction of adverse effects; modulation of immunity; prevention of cancer progression; and enhancement of symptom control. Although the database of preclinical studies is rapidly expanding, good-quality clinical trials are notably scarce.Laboratory studies suggest that some herbs increase the effectiveness of conventional chemotherapy without increasing toxicity. A healthy immune system is necessary for control of malignant disease, and the immune suppression associated with cancer contributes to its progression. Many Chinese herbs contain glycoproteins and polysaccharides (among them, constituents of Coriolus versicolor, Ganoderma lucidum, Grifola frondosa, Astragalus membranaceus, Panax ginseng, and various other medicinal mushrooms) that can modulate metastatic potential and the innate immune system. Phytochemicals such as specific polysaccharides have been shown to boost the innate immune system, especially through interaction with Tolllike receptors in mucosa-associated lymphoid tissue. This intervention can potentially improve the effectiveness of new anticancer vaccines. An increase in virusassociated cancers presents a major public health problem that requires novel therapeutic strategies. A number of herbal therapies have both antiviral activity and the ability to promote immunity, possibly inhibiting the initiation and promotion of virus-associated cancers.The mechanisms learned from basic science should be applied to clinical trials both of specific interventions and of whole-system care plans that safely combine the TCM approach with the conventional biomedical model. In Western medicine, the combination of TCM herbs with drug therapies is controversial, given lack of knowledge concerning whether a drug is favourably enhanced or whether adverse effects occur. Using initial data from the preclinical studies, future clinical research needs to evaluate the combinations, some of which are showing favourable synergy.

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Bilobalide and Neuroprotection

Cited by 132 publications

References 14 publications

Role of GABAergic antagonism in the neuroprotective effects of bilobalide

Role of GABAergic antagonism in the neuroprotective effects of bilobalide

Involvement of Ca2+, CaMK II and PKA in EGb 761-induced insulin secretion in INS-1 cells

Chinese Medicine and Biomodulation in Cancer Patients—Part Two

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