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Background: Because depression is a major factor contributing to the global disease burden, we tried to analyze the effects and safety of Ginkgo biloba GKB on patients with depression. A systematic literature review and meta-analysis were performed to compare the effects and safety of GKB on patients with depression, including subjective and objective indicators of depression evaluation. Results: In total, 21 eligible articles with nine indicators among patients were included. However, there were no differences in adverse events between GKB and controls. GKB might reduce the risk of depression or depressive symptoms with safe clinical efficacy. It is reported that a main factor contributing to the burden of disease throughout the world is mental illness Liu et al. The two most incapacitating mental diseases, depression and anxiety disorders, are among the top 25 major causes of global disease burden in , according to Global Burden of Disease GBD research Collaborators, Of these, depression is a severe mood disorder characterized by a dearth of pleasure, diminished capacity for pleasure, sleepiness or insomnia, psychomotor agitation or retardation, exhaustion, feelings of worthlessness or guilt, trouble concentrating, and recurrent thoughts of suicide or death Yuehua Li, ; Wang, According to WHO, depression is the presence of persistent sadness and the loss of interest in activities that one normally enjoys, accompanied by an inability to carry out daily activities for at least 2 weeks. It is different from the usual mood fluctuations or temporary sadness in response to challenges in everyday life Collaborators, After the COVID pandemic, respiratory-transmitted illnesses continue to generate concern about the implications on mental health due to their immediate psychological effects and long-term economic and societal repercussions Collaborators, Globally, economic activity is only slowly recovering, unemployment rates are rising, employment rates for young people—especially college students—are falling, and there are still widespread epidemics of respiratory diseases Yueyi Kan and Rao, We must continue to identify effective ways to lessen the negative effects of the final phase of the COVID pandemic on mental health, and we still need up-to-date data on the incidence and burden of mental illnesses across the world Zhang et al. Ginkgo is used to treat cerebral insufficiency and intermittent claudication. Ginkgo biloba extract EGb has been utilized extensively in the treatment of central nervous system conditions such as age-related cognitive decline and dementia, vestibular and non-vestibular vertigo, tinnitus, and peripheral artery occlusive disease Fournier et al. Because EGb is able to modify blood rheology to enhance blood flow as well as to promote neuroprotection and modulate neurotransmission, the mechanism of action behind these therapeutic benefits is complex Kasper, Additionally, it has been discovered that people with mental impairment who take EGb have less anxiety. Consequently, it is of significant clinical relevance to evaluate the efficacy and safety of GKB on mental health. There is still some debate about evaluating the use of ginkgo for depression treatment because there is not enough research on the herb, and not all reports agree that it works well. In order to undertake a systematic analysis with high confidence, the current study attempted to incorporate all trials on ginkgo for depression conducted globally over a year period. The main focus is to evaluate if GKB is effective and safe for depression, and we assume GKB is effective in ameliorating depression. Based on the PICO framework, we selected people with depression as patients. The intervention was GKB, and it was compared with placebo or traditional antipsychotics. After a thorough screening, 21 publications, released without language restriction between January and May , were included. Studies qualified if they included the following data: observational studies reporting clinical effectiveness, adverse events, and random control trials reporting depression assessments. Two authors Jingya Lin Xiaojing Sun extracted the data using a standardized data form after screening the titles, abstracts, and full texts of the publications identified by our search and assessing the risk of bias. Any discrepancies were discussed with a third author Lingli Yang. After the initial selection of the studies, the pertinent texts were examined, and the studies needed to fulfill the following criteria:. The following predetermined exclusion criteria were used to disqualify studies from consideration:. Using the ROB 2. Risk ratios RRs were computed for categorical outcomes. Our statistical analyses were conducted using R software version 4. Statistical significance was defined as a p -value of 0. We ran a sensitivity analysis, deleting one included article at a time, to assess the robustness of the final results. The research selection flowchart is depicted in Figure 1 , and the characteristics of the studies are listed in Table 1. The risk-of-bias evaluation for every included study is displayed in Supplementary Figures S1, S2. Based on the ROB 2. Of all the studies, 10 had more than patients, while 11 had less than The duration of the study varied from 1 to 4 years. All the research designs used in the included articles were randomized control trials RCTs. The median ages of the patients studied in the included articles ranged from There were nearly equal numbers of men and women men and 1, women. The specific traits of the included articles are displayed in Table 1. Only three articles had a high overall bias risk, six had a medium bias risk, and twelve had a low bias risk. The 6-week HAMD score was documented in seven studies. In addition to GKB therapy, we further investigate the serum indices and other depression scales. Finally, we assessed the clinical effectiveness and adverse events in the GKB and control groups. Begg funnel plots for the meta-analysis of adverse events were created to examine the publication bias. The funnel plots Figure 5 demonstrated visual symmetry and revealed a low level of publication bias in this study. Sensitivity analysis was done to verify that the results were reliable. We removed each article in turn from the sensitivity forest plot Figure 6. These findings suggested that the conclusions were sound. The HAMD is a scale developed by Max Hamilton in to assess the symptoms of patients diagnosed with depressive states Hamilton, Using HAMD as an assessment outcome, the Ginkgo biloba extract group had lower HAMD values than the control group at 4 weeks, 6 weeks, and 8 weeks after taking the medication. The efficacy of adding Ginkgo biloba extract to the traditional treatment regimen for depression may be better than the traditional treatment regimen. In the results of other scales about stroke in patients with depression, the GKB group had a higher MBI than the control group. Again, these findings supported that the GKB groups had better CNS co-functional activity than patients treated with traditional depression medicine. Previous research has shown that 5-HT abnormalities are connected to the etiology of depression Jaster et al. However, this link is disturbed when the brain is ischemic and hypoxic, which may result in decreased production of BDNF and 5-HT Kumar et al. BDNF is broadly distributed throughout the brain, including the cerebral cortex and hippocampus Kumar and Singh, ; Kumar and Singh, ; Kumar et al. It influences the release of neurotransmitters and trophic factors and encourages the differentiation and regeneration of injured neurons Singh et al. According to earlier research, BNDF is essential for preserving and fostering nerve fiber regeneration in monkey stroke models. Earlier research reported that BDNF plays a crucial role in the antidepressant effects of venlafaxine Brammanathan et al. Finally, the GKB group was also superior to the control group in terms of overall clinical efficacy. In the safety analysis results, no differences could be seen between the two groups. Regarding the comparative results in terms of adverse events, consistent with previous studies, there were no differences between the GKB and the control groups in terms of adverse events when treating depression and anxiety Zhang et al. The clinical efficacy and safety of GKB on depression was consistent with previous research Sarris et al. We list various potential causes for the heterogeneity in some of our results. First, the variability in GKB dose may have an impact. Second, the different study sites of the collected publications unquestionably add to the variability. Third, there is a chance that personnel and research measurement variations will contribute to heterogeneity. Overall, this study suggested that GKB could lower the risk of depression or depressed symptoms based on a sizable sample and several indications. GKB was safe for patients with depression at the same time. The current study had certain limitations. First, it was impossible to have a larger sample for each indication due to the variety of indicators reported in the included research. Second, comprehensive results for numerous populations were lacking because trials of GKB for patients with depression were not found in the United States or Europe. Last but not least, future indicators should contain more contemporary measurements like PHQ-9 and other biomarkers. JL: writing—original draft, methodology, formal analysis, and data curation. XS: writing—original draft, validation, and methodology. LY: writing—review and editing, validation, supervision, formal analysis, and conceptualization. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors, and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. Aijun Zhang, F. Effect of ginkgo honey ring oral liquid on colonization resistance of Gut microbiota and serum 5-HT in patients with depression after PCI of coronary heart disease. Traditional Chin. Binhua Chen, R. Contrast study of folium ginkgo preparation and citalopram combined treatment in vascular depression. Zhejiang Univ. Google Scholar. Brammanathan, S. Serum BDNF levels among patients with alcohol dependence, depression and alcohol dependence with comorbid depression - a comparative study. Drugs , 1—9. Collaborators, C. Global prevalence and burden of depressive and anxiety disorders in countries and territories in due to the COVID pandemic. Lancet , — Dai, C. Role of Ginkgo biloba extract as an adjunctive treatment of elderly patients with depression and on the expression of serum SB. Dou, L. The application of cecropram combined with ginkgo biloba extract in elderly coronary heart disease patients with depression. China Pract. Fengqing Yu, A. Clinical observation on ginkgo biloba leaf combined with prozac in the treatment of poststroke depression. Fournier, J. Antidepressant drug effects and depression severity: a patient-level meta-analysis. JAMA 1 , 47— Gabryelska, A. Gavrilova, S. Efficacy and safety of Ginkgo biloba extract EGb in mild cognitive impairment with neuropsychiatric symptoms: a randomized, placebo-controlled, double-blind, multi-center trial. Psychiatry 29 10 , — Gliwinska, A. The role of brain-derived neurotrophic factor BDNF in diagnosis and treatment of epilepsy, depression, schizophrenia, anorexia nervosa and Alzheimer's disease as highly drug-resistant diseases: a narrative review. Brain Sci. Haixia Wu, M. Evaluation of therapeutic effect of ginkgo biloba extract combined with Fluoxetine on depression after acute cerebral infarction. Hamilton, M. A rating scale for depression. Psychiatry 23 1 , 56— Hao Song, J. Analysis of the therapeutic effect of jieyu pill combined with ginkgo biloba capsule on post-stroke depression. Traditional Med. Hartley, D. Gincosan a combination of Ginkgo biloba and Panax ginseng : the effects on mood and cognition of 6 and 12 weeks' treatment in post-menopausal women. He, Z. Observation on the therapeutic effect of psychological intervention mode combined with ginkgo biloba leaves on post-stroke depression. Jaster, A. Effects of the 5-HT 2A receptor antagonist volinanserin on head-twitch response and intracranial self-stimulation depression induced by different structural classes of psychedelics in rodents. Jastrzebska, J. Evaluation of the 5-HT 2C receptor drugs RO , WAY and mirtazepine in a preclinical model of comorbidity of depression and cocaine addiction. Jia Yuan, L. Clinical study of Ginkgo biloba combined with interpersonal psychological intervention in the treatment of coronary heart disease with depression. New Drugs Clin. Jinyi, W. Global, regional, and national mortality of tuberculosis attributable to alcohol and tobacco from to a modelling study based on the Global Burden of Disease study Junfeng Yin, Z. Efficacy of butylphthalide combined with ginkgo biloba capsule in the treatment of Parkinson's disease with depression and Sleep disorder. Kasper, S. Phytopharmaceutical treatment of anxiety, depression, and dementia in the elderly: evidence from randomized, controlled clinical trials. Wien Med. Wochenschr , — Kefeng Guo, S. Clinical observation of ginkgo biloba leaves combined with Paroxetine in the treatment of depression. Rehabilitation 10 2 , 43— Kumar, D. Power Res. Effect of Hall current and wall conductance on hydromagnetic natural convective flow between vertical walls. Industrial Math. Procedia Eng. Alexandria Eng. Applications of fluid dynamics Singapore: Springer Singapore. Ambient Energy 43 1 , — Effect of Hall current on the magnetohydrodynamic free convective flow between vertical walls with induced magnetic field. Plus , — A Stat. Liang, Z. Efficacy of ginkgo biloba extract as augmentation of venlafaxine in treating post-stroke depression. Lin, C. Effects of Ginkgo biloba extract on depression and neurological function after acute cerebral infarction. Liu, Q. Changes in the global burden of depression from to findings from the global burden of disease study. Liu, Y. To explore the clinical efficacy of butylphthalide combined with ginkgo folic acid capsule in the treatment of Parkinson's disease with depression and Sleep disorder. Marcinkowska, M. ACS Chem. Mishra, M. Thermal radiation and Soret effects on boundary layer flow past a vertical surface embedded in porous medium with induced magnetic field with reference to aluminum industry. Analysis Calorim. Page, M. Panigrahi, L. Impact of chemical reaction, Hall current, and radiation on MHD flow between vertical walls. Popova, N. The implication of 5-HT receptor family members in aggression, depression and suicide: similarity and difference. Ru Liu, H. Efficacy evaluation of butylphthalide combined with ginkgo biloba capsule in the treatment of Parkinson's disease with depression and Sleep disorder. Sarris, J. Herbal medicine for depression, anxiety and insomnia: a review of psychopharmacology and clinical evidence. Shichao, J. Clinical efficacy of Ginkgo biloba and Damo injection as adjunctive therapy for depression disorder. Singh, S. Brain-derived neurotrophic factor BDNF in perinatal depression: side show or pivotal factor? Drug Discov. Today 28 2 , Tao, Q. Investigating the factors affecting the competence of a traditional Chinese medicine practitioner using structural equation model. Vyas, C. Relation of serum BDNF to major depression and exploration of mechanistic roles of serum BDNF in a study of vitamin D3 and omega-3 supplements for late-life depression prevention. Wang, J. Disease burden of depressive disorders in Beijing. Public Health 12 1 , 34— Wei Chen, M. Clinical observation of Fluoxetine hydrochloride combined with ginkgo biloba leaves in the treatment of post-stroke depression. Woelk, H. Ginkgo biloba special extract EGb in generalized anxiety disorder and adjustment disorder with anxious mood: a randomized, double-blind, placebo-controlled trial. Wu, J. The association of blood metals with latent tuberculosis infection among adults and adolescents. Xiangdong Luo, J. The efficacy of Paroxetine combined with ginkgo biloba leaves in the treatment of vascular depression. West China 23 9 , — Effect of Paroxetine combined with ginkgo biloba leaves on serum BDNF in patients with vascular depression. Sichuan Med. Xiaonan Zhang, S. Anti depression effect of ginkgo. Yadav, S. Magnetohydrodynamic flow in horizontal concentric cylinders. Yeung, K. Herbal medicine for depression and anxiety: a systematic review with assessment of potential psycho-oncologic relevance. Yuehua Li, F. Current status and future research objectives of depression research. Yueyi Kan, M. Research progress on antidepressant effects of Ginkgo biloba and its active ingredients. Zhang, W. Medicinal herbs for the treatment of anxiety: a systematic review and network meta-analysis. Zhang, Y. Clinical study of ginkgo biloba and Eleutherococcus senticosus injection in the treatment of depression after cerebral infarction. A network suspected infectious disease model for the development of syphilis transmission from to in Hubei province, China. Zheng, X. Analysis of factors and corresponding interactions influencing clinical management assistant ability using competency model in China. Medicine 99 51 , e Keywords: Ginkgo biloba , GKB, depression, depressive symptoms, meta-analysis. The use, distribution or reproduction in other forums is permitted, provided the original author s and the copyright owner s are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher. Top bar navigation. About us About us. Sections Sections. About journal About journal. Article types Author guidelines Editor guidelines Publishing fees Submission checklist Contact editorial office. Effects and safety of Ginkgo biloba on depression: a systematic review and meta-analysis. Introduction It is reported that a main factor contributing to the burden of disease throughout the world is mental illness Liu et al. Inclusion and exclusion criteria After the initial selection of the studies, the pertinent texts were examined, and the studies needed to fulfill the following criteria: 1 Studies that compared GKB and a control for the treatment of depression; 2 The design of research should be randomized control trials; 3 Containing indicators evaluating the efficacy and safety of GKB on depression; 4 Available in full text. The following predetermined exclusion criteria were used to disqualify studies from consideration: 1 Research on other drugs; 2 Other topics about depression; 3 Study lacking available data; 4 Review, abstract, or duplicate publication. TABLE 1. Main characteristics of the included studies. TABLE 2. Chemical component of the included studies. Funnel plot for potential publication bias. Sensitivity analysis by omitting each article in turn.
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