Ginkgolide A Prevents the Amyloid-β-Induced Depolarization of Cortical Neurons

Kuo, Li Chen; Song, Yan Qing; Yao, Chien‐An; Cheng, Irene H.; Chien, Chiang Ting; Lee, Guan Chiun; Yang, Wu-Chang; Lin, Yenshou

doi:10.1021/acs.jafc.8b04514

Cited by 27 publications

(20 citation statements)

References 36 publications

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“…Previous studies have shown that EGb is effective in the prevention and treatment of aging-related diseases [12][13][14].…”

Section: Discussionmentioning

confidence: 99%

“…EGb preparation is a relatively successful case of plant medicine developed by modern science and technology and occupies an important position in the field of antiaging and clinical medication for cardiovascular and cerebrovascular diseases [ 9 , 11 ]. Previous studies have shown that EGb has certain efficacy in the prevention and treatment of age-related diseases [ 9 , 12 – 14 ]. However, the pharmacologic profiles of EGB for aging remain unclear.…”

Section: Introductionmentioning

confidence: 99%

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Network Pharmacology‐Based Strategy to Investigate the Pharmacological Mechanisms of Ginkgo biloba Extract for Aging

Liu

Zhang

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Aging is a main risk factor for a number of debilitating diseases and contributes to an increase in mortality. Previous studies have shown that Ginkgo biloba extract (EGb) can prevent and treat aging-related diseases, but its pharmacological effects need to be further clarified. This study aimed to propose a network pharmacology-based method to identify the therapeutic pathways of EGb for aging. The active components of EGb and targets of sample chemicals were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database. Information on aging-related genes was obtained from the Human Ageing Genomic Resources database and JenAge Ageing Factor Database. Subsequently, a network containing the interactions between the putative targets of EGb and known therapeutic targets of aging was established, which was used to investigate the pharmacological mechanisms of EGb for aging. A total of 24 active components, 154 targets of active components of EGb, and 308 targets of aging were obtained. Network construction and pathway enrichment were conducted after data integration. The study found that flavonoids (quercetin, luteolin, and kaempferol) and beta-sitosterol may be the main active components of EGb. The top eight candidate targets, namely, PTGS2, PPARG, DPP4, GSK3B, CCNA2, AR, MAPK14, and ESR1, were selected as the main therapeutic targets of EGb. Pathway enrichment results in various pathways were associated with inhibition of oxidative stress, inhibition of inflammation, amelioration of insulin resistance, and regulation of cellular biological processes. Molecular docking results showed that PPARG had better binding capacity with beta-sitosterol, and PTGS2 had better binding capacity with kaempferol and quercetin. The main components of EGb may act on multiple targets, such as PTGS2, PPARG, DPP4, and GSK3B, to regulate multiple pathways, and play an antiaging role by inhibiting oxidative stress, inhibiting inflammation, and ameliorating insulin resistance.

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“…Previous studies have shown that EGb is effective in the prevention and treatment of aging-related diseases [12][13][14].…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Network Pharmacology‐Based Strategy to Investigate the Pharmacological Mechanisms of Ginkgo biloba Extract for Aging

Liu

Zhang

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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show abstract

“…The results were shown in Additional le 1: Chemical information of main compounds in EGb. The OB of ginkgolide A was < 30%, but it was a common compound in EGb and shown to have effects on prevention and treatment of Alzheimer's disease (AD), a disease associated with aging [23,24]. Hence, ginkgolide A was also considered to be a candidate compound.…”

Section: Identifcation Of the Active Compounds In Egbmentioning

confidence: 99%

“…EGb preparation is a relatively successful case of plant medicine developed by modern science and technology, and occupies an important position in the eld of anti-aging and clinical medication for cardiovascular and cerebrovascular diseases [9,11]. Previous studies have shown that EGb has certain e cacy in the prevention and treatment of age-related diseases [9,[12][13][14]. However, its pharmacologic pro les of EGB for aging remain to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

Network pharmacology-based strategy to investigate pharmacological mechanisms of Ginkgo Biloba Extract for Aging

Liu

Zhang

et al. 2020

Preprint

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Background Aging represents the main risk factor for a number of debilitating diseases and contributes to increase in mortality. Previous studies have shown that ginkgo biloba extract (EGb) can prevent and treat aging-related diseases, but its pharmacological effects need to be further clarified. In this study, we proposed a network pharmacology-based method to identify the therapeutic pathways of EGb for aging.Methods The active components of EGb and targets of sample chemicals were obtained from TCMSP database. Aging-related genes were obtained by retrieving the Human Ageing Genomic Resources database and the JenAge Ageing Factor Database. Then, a network containing the interactions between the putative targets of EGb and known therapeutic targets of aging was built, which was used to investigate pharmacological mechanisms of EGb for Aging.Results 24 active components, 154 targets of active components of EGb and 308 targets of aging were obtained. Network construction and pathway enrichment were carried out after data integration. The research found that flavonoids (quercetin, luteolin, kaempferol) and beta-sitosterol might be the main active component of EGb. The top eight candidate targets, including PTGS2, PPARG, DPP4, GSK3B, CCNA2, AR, MAPK14, ESR1, were chosen as EGb’s main therapeutic targets. The results of pathway enrichment participated in various pathways associated with inhibiting oxidative stress, inhibiting inflammation, ameliorating insulin resistance and regulating cellular biological processes, etc. Molecular docking results showed that PPARG had better binding capacity with beta-sitosterol and PTGS2 had better binding capacity with kaempferol and quercetin.Conclusions The main components of EGb might act on multiple targets, such as PTGS2, PPARG, DPP4, GSK3B, etc., to regulate multiple pathways and played an anti- aging role by inhibiting oxidative stress, inhibiting inflammation, ameliorating insulin resistance.

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“…Ginkgo biloba is also considered as a neuroprotective agent. Ginkgolide A inhibits Aβ-induced neuronal degradation via JNK phosphorylation and NMDA/AMPA-induced depolarization, thus suppress the activity of plaque [43]. EGb 761 increases the neurogenesis in the adult hippocampus region and CREB phosphorylation in the transgenic mouse model of AD [44].…”

Section: Alzheimer's Disease and Related Dementiasmentioning

confidence: 99%

Neuroprotection: Targeting Multiple Pathways by Naturally Occurring Phytochemicals

et al. 2020

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With the increase in the expectancy of the life span of humans, neurodegenerative diseases (NDs) have imposed a considerable burden on the family, society, and nation. In defiance of the breakthroughs in the knowledge of the pathogenesis and underlying mechanisms of various NDs, very little success has been achieved in developing effective therapies. This review draws a bead on the availability of the nutraceuticals to date for various NDs (Alzheimer’s disease, Parkinson’s disease, Amyotrophic lateral sclerosis, Huntington’s disease, vascular cognitive impairment, Prion disease, Spinocerebellar ataxia, Spinal muscular atrophy, Frontotemporal dementia, and Pick’s disease) focusing on their various mechanisms of action in various in vivo and in vitro models of NDs. This review is distinctive in its compilation to critically review preclinical and clinical studies of the maximum phytochemicals in amelioration and prevention of almost all kinds of neurodegenerative diseases and address their possible mechanism of action. PubMed, Embase, and Cochrane Library searches were used for preclinical studies, while ClinicalTrials.gov and PubMed were searched for clinical updates. The results from preclinical studies demonstrate the efficacious effects of the phytochemicals in various NDs while clinical reports showing mixed results with promise for phytochemical use as an adjunct to the conventional treatment in various NDs. These studies together suggest that phytochemicals can significantly act upon different mechanisms of disease such as oxidative stress, inflammation, apoptotic pathways, and gene regulation. However, further clinical studies are needed that should include the appropriate biomarkers of NDs and the effect of phytochemicals on them as well as targeting the appropriate population.

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Ginkgolide A Prevents the Amyloid-β-Induced Depolarization of Cortical Neurons

Cited by 27 publications

References 36 publications

Network Pharmacology‐Based Strategy to Investigate the Pharmacological Mechanisms of Ginkgo biloba Extract for Aging

Network Pharmacology‐Based Strategy to Investigate the Pharmacological Mechanisms of Ginkgo biloba Extract for Aging

Network pharmacology-based strategy to investigate pharmacological mechanisms of Ginkgo Biloba Extract for Aging

Neuroprotection: Targeting Multiple Pathways by Naturally Occurring Phytochemicals

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