The Use of Ginkgo Biloba L. as a Neuroprotective Agent in the Alzheimer’s Disease

Nowak, Anna; Kojder, Klaudyna; Zielonka-Brzezicka, Joanna; Wróbel, Jacek; Bosiacki, Mateusz; Fabiańska, Marta; Wróbel, Mariola; Sołek-Pastuszka, Joanna; Klimowicz, Adam

doi:10.3389/fphar.2021.775034

Cited by 51 publications

(28 citation statements)

References 165 publications

(231 reference statements)

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“…AD is characterized by cognitive impairment whereby neurotoxic Aβ oligomers contribute to its onset and progression ( Lambert et al, 1998 ). Commonly applied medicines include cholinesterase inhibitors, e.g., donepezil, galantamine, and rivastigmine, the N -methyl-D-aspartate-receptor-antagonist memantine, and Ginkgo biloba extract EGb 761 ( Liu et al, 2015 ; Sharma et al, 2019 ; Nowak et al, 2021 ). However, none of these therapeutics is able to alleviate the causative disorder, but only delay the progression of symptoms related to AD.…”

Section: Introductionmentioning

confidence: 99%

Azepine-Indole Alkaloids From Psychotria nemorosa Modulate 5-HT2A Receptors and Prevent in vivo Protein Toxicity in Transgenic Caenorhabditis elegans

et al. 2022

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Nemorosine A (1) and fargesine (2), the main azepine-indole alkaloids of Psychotria nemorosa, were explored for their pharmacological profile on neurodegenerative disorders (NDs) applying a combined in silico–in vitro–in vivo approach. By using 1 and 2 as queries for similarity-based searches of the ChEMBL database, structurally related compounds were identified to modulate the 5-HT2A receptor; in vitro experiments confirmed an agonistic effect for 1 and 2 (24 and 36% at 10 μM, respectively), which might be linked to cognition-enhancing properties. This and the previously reported target profile of 1 and 2, which also includes BuChE and MAO-A inhibition, prompted the evaluation of these compounds in several Caenorhabditis elegans models linked to 5-HT modulation and proteotoxicity. On C. elegans transgenic strain CL4659, which expresses amyloid beta (Aβ) in muscle cells leading to a phenotypic paralysis, 1 and 2 reduced Aβ proteotoxicity by reducing the percentage of paralyzed worms to 51%. Treatment of the NL5901 strain, in which α-synuclein is yellow fluorescent protein (YFP)-tagged, with 1 and 2 (10 μM) significantly reduced the α-synuclein expression. Both alkaloids were further able to significantly extend the time of metallothionein induction, which is associated with reduced neurodegeneration of aged brain tissue. These results add to the multitarget profiles of 1 and 2 and corroborate their potential in the treatment of NDs.

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Section: Introductionmentioning

confidence: 99%

Azepine-Indole Alkaloids From Psychotria nemorosa Modulate 5-HT2A Receptors and Prevent in vivo Protein Toxicity in Transgenic Caenorhabditis elegans

et al. 2022

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“…The mechanism of action of Ginkgo biloba may proceed through multiple pathways, including antioxidative stress, regulation function of mitochondria and anti-inflammation ( 40-42 ). However, Ginkgo biloba contains numerous types of chemical components, such as terpenoids, biflavones and flavonols ( 42 ). Furthermore, among the active ingredients of Ginkgo biloba , terpenoids include the main diterpene ginkgolides A, B, C, J, M, K and L ( 43 ).…”

Section: Discussionmentioning

confidence: 99%

Effect of ginkgolide K on calcium channel activity in Alzheimer's disease

Liu

Zhang

et al. 2022

Exp Ther Med

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Alzheimer's disease (AD) is a progressive neurodegenerative dementia with the key pathological hallmark of amyloid deposits that may induce mitochondrial dysfunction. Ginkgolide K (GK) has been proven to have neuroprotective effects. The present study sought to explore the neuroprotective effect of GK through regulation of the expression of mitochondrial Ca 2+ uniporter (MCU) in the pathology of AD. SH-SY5Y cells were cultured and the expression of MCU was enhanced by transfection of MCU recombinant vectors or knockdown by MCU small interfering RNA. The cells were treated with GK and amyloid β (Aβ). Thereafter, the effects of GK, MCU expression and Aβ on viability and apoptosis of SH-SY5Y cells were examined via a WST-1 assay, flow cytometry and Caspase-3/8 activity assays, respectively. The effects of GK, MCU expression and Aβ on the calcium levels in mitochondria were also examined. The regulatory effect of GK on MCU expression was examined by reverse transcription-quantitative PCR and western blot analysis. Furthermore, APP/PS1 mice received supplementation with GK and their cognitive ability was then examined through water maze tests, while the expression of MCU was examined using immunohistochemistry. The results indicated that enhancing the expression of MCU inhibited cell viability and promoted apoptosis. GK protected cells from amyloid-induced cytotoxicity by promoting cell viability and preventing cell apoptosis. The neuroprotective effect of GK was abolished when MCU expression was knocked down. GK decreased the expression of MCU in vitro and downregulation of MCU decreased the calcium level in mitochondria. Treatment with GK in APP/PS1 mice downregulated the expression of MCU in the brains and alleviated cognitive impairment. In conclusion, the present study demonstrated that the administration of GK protected neurons by preventing apoptosis. Furthermore, the neuroprotective effect of GK in neuronal cells was indicated to be related to the inhibition of MCU expression. Therefore, administration of GK may be a promising strategy for treating AD.

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“…EGb is already used in the treatment of AD and cognitive deficits acting as anti-aggregating and pro-cognitive preparation. It is implemented to improve memory impairment and cognitive decline [ 11 ]. However, less attention and research are concentrated on its effect on immune system functioning in AD patients.…”

Section: Introductionmentioning

confidence: 99%

Ginkgo Biloba Leaf Extract Improves an Innate Immune Response of Peripheral Blood Leukocytes of Alzheimer’s Disease Patients

et al. 2022

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Background: One of the main features of Alzheimer's disease (AD) pathology is failure in innate immune response and chronic inflammation. Lack of effective AD treatment means that more attention is paid to alternative therapy and drugs of natural origin, such as extract of Ginkgo biloba (EGb). The purpose of this study was to investigate the effect of EGb on the mechanisms of innate immune response of peripheral blood leukocytes (PBLs) in AD patients. Methods: In AD patients and healthy-age matched controls, the effect of EGb on two of innate immune reactions, i.e., PBLs resistance to viral infection ex vivo and production of cytokines, namely TNF-α, IFN-γ, IL-1β, IL-10, IL-15, and IFN-α, were investigated. The influence of EGb on inflammatory-associated genes expression that regulate innate immune response to viral infection and cytokine production, namely IRF-3, IRF-7, tetherin, SOCS1, SOCS3, NFKB1, p65, and MxA was also examined. Results: A beneficial effect of EGb especially in AD women was observed. EGb decreased production of TNF-α, IFN-γ, and IL-10 and increased IL-15 and IL-1β. The effect was more pronouncement in AD group. EGb also downregulated expression of investigated genes. Conclusions: EGb may have an advantageous properties for health management in elderly and AD sufferers but especially in women with AD. Improving peripheral innate immune cells’ activity by adding EGb as accompanying treatment in AD may be, in the long term, a good course to modify the disease progression.

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The Use of Ginkgo Biloba L. as a Neuroprotective Agent in the Alzheimer’s Disease

Cited by 51 publications

References 165 publications

Azepine-Indole Alkaloids From Psychotria nemorosa Modulate 5-HT2A Receptors and Prevent in vivo Protein Toxicity in Transgenic Caenorhabditis elegans

Azepine-Indole Alkaloids From Psychotria nemorosa Modulate 5-HT2A Receptors and Prevent in vivo Protein Toxicity in Transgenic Caenorhabditis elegans

Effect of ginkgolide K on calcium channel activity in Alzheimer's disease

Ginkgo Biloba Leaf Extract Improves an Innate Immune Response of Peripheral Blood Leukocytes of Alzheimer’s Disease Patients

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