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      Advances in the Studies of Ginkgo Biloba Leaves Extract on Aging-Related Diseases

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          Abstract

          The prevalence of degenerative disorders in public health has promoted in-depth investigations of the underlying pathogenesis and the development of new treatment drugs. Ginkgo biloba leaves extract (EGb) is obtained from Ginkgo biloba leaves and has been used for thousands of years. In recent decades, both basic and clinical studies have established the effects of EGb. It is widely used in various degenerative diseases such as cerebrovascular disease, Alzheimer’s disease, macroangiopathy and more. Here, we reviewed several pharmacological mechanisms of EGb, including its antioxidant properties, prevention of mitochondrial dysfunctions, and effect on apoptosis. We also described some clinical applications of EGb, such as its effect on neuro and cardiovascular protection, and anticancer properties. The above biological functions of EGb are mainly focused on aging-related disorders, but its effect on other diseases remains unclear. Thus, through this review, we aim to encourage further studies on EGb and discover more potential applications

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          The involvement of BDNF, NGF and GDNF in aging and Alzheimer's disease.

          Josiane Budni, Tatiani Bellettini-Santos, Francielle Mina … (2015)
          Aging is a normal physiological process accompanied by cognitive decline. This aging process has been the primary risk factor for development of aging-related diseases such as Alzheimer's disease (AD). Cognitive deficit is related to alterations of neurotrophic factors level such as brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and glial cell-derived neurotrophic factor (GDNF). These strong relationship between aging and AD is important to investigate the time which they overlap, as well as, the pathophysiological mechanism in each event. Considering that aging and AD are related to cognitive impairment, here we discuss the involving these neurotrophic factors in the aging process and AD.
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            Long-term use of standardised Ginkgo biloba extract for the prevention of Alzheimer's disease (GuidAge): a randomised placebo-controlled trial.

            Bruno Vellas, Nicola Coley, Pierre-Jean Ousset … (2012)
            Prevention strategies are urgently needed to tackle the growing burden of Alzheimer's disease. We aimed to assess efficacy of long-term use of standardised ginkgo biloba extract for the reduction of incidence of Alzheimer's disease in elderly adults with memory complaints. In the randomised, parallel-group, double-blind, placebo-controlled GuidAge clinical trial, we enrolled adults aged 70 years or older who spontaneously reported memory complaints to their primary-care physician in France. We randomly allocated participants in a 1:1 ratio according to a computer-generated sequence to a twice per day dose of 120 mg standardised ginkgo biloba extract (EGb761) or matched placebo. Participants and study investigators and personnel were masked to study group assignment. Participants were followed-up for 5 years by primary-care physicians and in expert memory centres. The primary outcome was conversion to probable Alzheimer's disease in participants who received at least one dose of study drug or placebo, compared by use of the log-rank test. This study is registered with ClinicalTrials.gov, number NCT00276510. Between March, 2002, and November, 2004, we enrolled and randomly allocated 2854 participants, of whom 1406 received at least one dose of ginkgo biloba extract and 1414 received at least one dose of placebo. By 5 years, 61 participants in the ginkgo group had been diagnosed with probable Alzheimer's disease (1·2 cases per 100 person-years) compared with 73 participants in the placebo group (1·4 cases per 100 person-years; hazard ratio [HR] 0·84, 95% CI 0·60-1·18; p=0·306), but the risk was not proportional over time. Incidence of adverse events was much the same between groups. 76 participants in the ginkgo group died compared with 82 participants in the placebo group (0·94, 0·69-1·28; p=0·68). 65 participants in the ginkgo group had a stroke compared with 60 participants in the placebo group (risk ratio 1·12, 95% CI 0·77-1·63; p=0·57). Incidence of other haemorrhagic or cardiovascular events also did not differ between groups. Long-term use of standardised ginkgo biloba extract in this trial did not reduce the risk of progression to Alzheimer's disease compared with placebo. Ipsen. Copyright © 2012 Elsevier Ltd. All rights reserved.
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              Mitochondrial oxidative stress plays a key role in aging and apoptosis.

              J. Sastre, J. Viña, F Pallardo (2000)
              Harman first suggested in 1972 that mitochondria might be the biological clock in aging, noting that the rate of oxygen consumption should determine the rate of accumulation of mitochondrial damage produced by free radical reactions. Later in 1980 Miquel and coworkers proposed the mitochondrial theory of cell aging. Mitochondria from postmitotic cells use O2 at a high rate, hence releasing oxygen radicals that exceed the cellular antioxidant defences. The key role of mitochondria in cell aging has been outlined by the degeneration induced in cells microinjected with mitochondria isolated from fibroblasts of old rats, especially by the inverse relationship reported between the rate of mitochondrial production of hydroperoxide and the maximum life span of species. An important change in mitochondrial lipid composition is the age-related decrease found in cardiolipin content. The concurrent enhancement of lipid peroxidation and oxidative modification of proteins in mitochondria further increases mutations and oxidative damage to mitochondrial DNA (mtDNA) in the aging process. The respiratory enzymes containing the defective mtDNA-encoded protein subunits may increase the production of reactive oxygen species, which in turn would aggravate the oxidative damage to mitochondria. Moreover, superoxide radicals produced during mitochondrial respiration react with nitric oxide inside mitochondria to yield damaging peroxynitrite. Treatment with certain antioxidants, such as sulphur-containing antioxidants, vitamins C and E, or the Ginkgo biloba extract EGb 761, protects against the age-associated oxidative damage to mtDNA and the oxidation of mitochondrial glutathione. Moreover, the EGb 761 extract also prevents changes in mitochondrial morphology and function associated with aging of the brain and liver.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Aging Dis
                Journal ID (iso-abbrev): Aging Dis
                Title: Aging and Disease
                Publisher: JKL International LLC
                ISSN (Electronic): 2152-5250
                Publication date Collection: December 2017
                Publication date (Electronic): 1 December 2017
                Volume: 8
                Issue: 6
                Pages: 812-826
                Affiliations
                [1-ad-8-6-812] 1Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
                [2-ad-8-6-812] 2Cerebrovascular Diseases Research Institute, Xuanwu Hospital of Capital Medical University, Beijing, China
                [3-ad-8-6-812] 3Department of Neurobiology, Capital Medical University, Beijing, China
                Author notes
                [* ]Correspondence should be addressed to: Dr. Dan Mei, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China, 100730. Email: meidanpumch@ 123456163.com
                Article
                Publisher ID: ad-8-6-812
                DOI: 10.14336/AD.2017.0615
                PMC ID: 5758353
                PubMed ID: 29344418
                SO-VID: b0f765bc-4223-48ea-8946-71ed81dea49b
                Copyright © Copyright: © 2017 Zuo et al.
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

                History
                Date received : 7 December 2016
                Date revision requested : 29 May 2017
                Date accepted : 15 June 2017
                Categories
                Subject: Review

                Keywords: ginkgo biloba leaves extract,degenerative disorders,antioxidant,neuron protection,anticancer,cardiovascular
                Data availability:
                Keywords: ginkgo biloba leaves extract, degenerative disorders, antioxidant, neuron protection, anticancer, cardiovascular

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