Meta-Analysis of the Efficacy and Safety of Intravenous Ginkgo Biloba Leaf Preparation in the Treatment of Acute Ischemic Stroke

doi:10.3969/j.issn.1673-5765.2025.04.010

Abstract

Abstract: Objective To systematically evaluate the efficacy and safety of intravenous ginkgo biloba leaf preparation in the treatment of acute ischemic stroke (AIS).
Methods Randomized controlled trials of intravenous ginkgo biloba leaf preparation in the treatment of AIS in English databases such as PubMed, Embase, and Cochrane Library, as well as in Chinese databases like Wanfang, CNKI, and VIP were searched by computer. The search period was from the establishment of these databases to July 30, 2024. The quality of the included literature was evaluated using the Cochrane RevMan bias risk assessment table. Using RevMan 5.3 software, a meta-analysis was performed on prognosis, early neurological improvement, neurological deficits, total effective rate, adverse reactions, and other indicators of ginkgo biloba leaf preparation in the treatment of AIS.
Results A total of 9 articles were included in this study, including 3 in English and 6 in Chinese, which involved 6111 patients, comprising 3103 in the control group and 3008 in the experimental group. The meta-analysis results showed that intravenous ginkgo biloba leaf preparation could improve the rate of good prognosis (mRS score≤2 points) of AIS patients (OR 1.95, 95%CI 1.72-2.22, P＜0.001), reduce the mRS score [standardized mean difference (SMD) －0.67, 95%CI －0.76-－0.58, P＜0.001], enhance the rate of early neurological improvement of patients (OR 1.23, 95%CI 1.07-1.41, P=0.003), and decrease the NIHSS score of patients (SMD －1.36, 95%CI －1.54-－1.17, P＜0.001). Ginkgo biloba leaf preparation could improve the total effective rate of AIS treatment (OR 3.68, 95%CI 1.81-7.49, P＜0.001), without increasing the incidence of adverse reactions (OR 1.01, 95%CI 0.85-1.20, P=0.870).
Conclusions Intravenous ginkgo biloba leaf preparation has a brain cytoprotection effect on AIS and can improve the prognosis of patients without increasing adverse reactions.

Key words: Acute ischemic stroke; Ginkgo biloba leaf preparation; Neurological function; Prognosis; Adverse reaction

摘要： 目的系统评价静脉应用银杏叶制剂治疗急性缺血性卒中（acute ischemic stroke，AIS）的有效性和安全性。
方法计算机检索PubMed、Embase、Cochrane Library等英文数据库，以及万方、中国知网、维普等中文数据库，分析银杏叶制剂静脉注射治疗AIS的随机对照试验，检索时限为建库至2024年7月30日。使用Cochrane RevMan偏倚风险评估表评价纳入研究的质量。使用RevMan 5.3软件，对银杏叶制剂治疗AIS的预后、早期神经功能改善、神经功能缺损、总有效率、不良反应等指标进行meta分析。
结果本研究共纳入9篇文献，其中英文文献3篇，中文文献6篇，共6111例患者，其中对照组3103例，试验组3008例。meta分析结果显示，静脉应用银杏叶制剂可提高AIS患者的预后良好（mRS评分≤2分）率（OR 1.95，95%CI 1.72～2.22，P＜0.001），降低mRS评分[标准化均数差（standardized mean difference，SMD）－0.67，95%CI －0.76～－0.58，P＜0.001]，提高患者的早期神经功能改善率（OR 1.23，95%CI 1.07～1.41，P=0.003），降低患者的NIHSS评分（SMD －1.36，95%CI －1.54～－1.17，P＜0.001）。另外，静脉应用银杏叶制剂可以提高AIS治疗的总有效率（OR 3.68，95%CI 1.81～7.49，P＜0.001），且不增加不良反应的发生率（OR 1.01，95%CI 0.85～1.20，P=0.870）。
结论静脉应用银杏叶制剂对AIS具有脑细胞保护作用，可改善患者的预后，且不增加不良反应。

关键词: 急性缺血性卒中; 银杏叶提取物; 神经功能; 预后; 不良反应

CLC Number:

HU Yanqin, ZHAO Taoli, LI Shen, GUO Dongxing, ZHAO Zhigang. Meta-Analysis of the Efficacy and Safety of Intravenous Ginkgo Biloba Leaf Preparation in the Treatment of Acute Ischemic Stroke[J]. Chinese Journal of Stroke, 2025, 20(4): 462-469.

胡燕琴, 赵陶丽, 李申, 郭东兴, 赵志刚. 静脉应用银杏叶制剂治疗急性缺血性卒中有效性和安全性的meta分析[J]. 中国卒中杂志, 2025, 20(4): 462-469.

References

[1] IADECOLA C，SMITH E E，ANRATHER J，et al. The neurovasculome：key roles in brain health and cognitive impairment：a scientific statement from the American Heart Association/American Stroke Association[J/OL]. Stroke，2023，54（6）：e251-e271[2025-01-01]. https://doi.org/10.1161/STR.0000000000000431.
[2] WECHSLER L R，ADEOYE O，ALEMSEGED F，et al. Most promising approaches to improve stroke outcomes：the Stroke Treatment Academic Industry Roundtable Ⅻ Workshop[J]. Stroke，2023，54（12）：3202-3213.
[3] 逯丹，陈玮琪，王雅平，等. 缺血性卒中脑细胞保护科学声明——来自中国卒中学会的科学声明[J]. 中国卒中杂志，2024，19（8）：938-955.
LU D，CHEN W Q，WANG Y P，et al. Scientific statements on brain cytoprotection in ischemic stroke—a scientific statement from the Chinese Stroke Association[J]. Chin J Stroke，2024，19（8）：938-955.
[4] SCHMIDT-POGODA A，BONBERG N，KOECKE M H M，et al. Why most acute stroke studies are positive in animals but not in patients：a systematic comparison of preclinical，early phase，and phase 3 clinical trials of neuroprotective agents[J]. Ann Neurol，2020，87（1）：40-51.
[5] ZHANG Q，WANG A X，XU Q，et al. Efficacy and safety of ginkgo diterpene lactone meglumine in acute ischemic stroke：a randomized clinical trial[J/OL]. JAMA Netw Open，2023，6（8）：e2328828[2025-01-01]. https://doi.org/10.1001/jamanetworkopen.2023.28828.
[6] ZHANG X T，ZHANG W S，MA X D，et al. Ginkgolide with intravenous alteplase thrombolysis in acute ischemic stroke improving neurological function：a multicenter，cluster-randomized trial（GIANT）[J/OL]. Front Pharmacol，2021，12：792136[2025-01-01]. https://doi.org/10.3389/fphar.2021.792136.
[7] DONG Y，LI H Q，DONG Q et al. The effect of intravenous ginkgolide on clinical improvement of patients with acute ischemic stroke[J]. Neurol Res，2020，42（3）：260-266.
[8] 张晶，周绍洪，罗明建，等. 银杏叶提取物注射液联合常规治疗对急性脑梗死后血管再生、侧支循环建立的影响[J]. 中国医院用药评价与分析，2022，22（10）：1196-1200.
ZHANG J，ZHOU S H，LUO M J，et al. Effects of ginkgo biloba extract injection combined with conventional treatment on vascular regeneration and collateral circulation after cerebral infarction[J]. Evaluation and Analysis of Drug-Use in Hospitals of China，2022，22（10）：1196-1200.
[9] 高云峰，张亮. 银杏叶提取物注射液联合尤瑞克林治疗急性脑梗死患者的效果[J]. 中国民康医学，2024，36（19）：92-95.
GAO Y F，ZHANG L. Effects of ginkgo biloba extract injection combined with urinary kallindinogenase in treatment of patients with acute cerebral infarction[J]. Medical Journal of Chinese People’s Health，2024，36（19）：92-95.
[10] 宋秋英，陶陈娟. 银杏叶提取物联合尼麦角林对急性缺血性脑卒中患者的临床研究[J]. 中国临床药理学杂志，2021，37（5）：499-502.
SONG Q Y，TAO C J. Clinical trial of ginkgo biloba extract combined with nicergoline in patients with acute ischemic stroke[J]. Chin J Clin Pharmacol，2021，37（5）：499-502.
[11] 王晓勇，骆守真，崔春丽. 银杏二萜内酯葡胺注射液治疗急性脑梗死临床研究[J]. 河北中医，2017，39（9）：1328-1331.
WANG X Y，LUO S Z，CUI C L. Clinical study on the treatment of acute cerebral infarction by ginkgo diterpene lactone meglumine injection[J]. Hebei J TCM，2017，39（9）：1328-1331.
[12] 刘志用. 丁苯酞联合银杏叶提取物注射液治疗对急性缺血性脑卒中患者神经功能及日常生活能力的影响[J]. 现代诊断与治疗，2024，35（5）：691-693.
LIU Z Y. Effects of butylphthalein combined with ginkgo biloba extract injection on neurological function and daily living ability in patients with acute ischemic stroke[J]. Mod Diagn Treat，2024，35（5）：691-693.
[13] 宋如敏，郭伟伟. 银杏叶提取物注射液联合西药治疗急性缺血性卒中的临床研究[J]. 现代诊断与治疗，2024，35（13）：1957-1958，1975.
SONG R M，GUO W W. Clinical study of ginkgo biloba extract injection combined with western medicine in the treatment of acute ischemic stroke[J]. Mod Diagn Treat，2024，35（13）：1957-1958，1975.
[14] ZHU T，WANG L，WANG L P，et a1. Therapeutic targets of neuroprotection and neurorestoration in ischemic stroke：applications for natural compounds from medicinal herbs[J/OL]. Biomed Pharmacother，2022，148：112719[2025-0l-01]. https://doi.org/10.1016/j.biopha.2022.112719.
[15] XIONG Y Y，WAKHLOO A K，FISHER M. Advances in acute ischemic stroke therapy[J]. Circ Res，2022，130（8）：1230-1251.
[16] YE H B，MA Z F，LIU L，et al. Thrombus inhibition and neuroprotection for ischemic stroke treatment through platelet regulation and ROS scavenging[J/OL]. ChemMedChem，2022，17（24）：e202200317[2025-01-01]. https://doi.org/10.1002/cmdc.202200317.
[17] LI B，ZHANG B K，LI Z Y，et al. Ginkgolide C attenuates cerebral ischemia/reperfusion-induced inflammatory impairments by suppressing CD40/NF-κB pathway[J/OL]. J Ethnopharmacol，2023，312：116537[2025-01-01]. https://doi.org/10.1016/j.jep.2023.116537.
[18] FAN X X，CAO Z Y，LIU M X，et al. Diterpene ginkgolides meglumine injection inhibits apoptosis induced by optic nerve crush injury via modulating MAPKs signaling pathways in retinal ganglion cells[J/OL]. J Ethnopharmacol，2021，279：114371[2025-01-01]. https://doi.org/10.1016/j.jep.2021.114371.
[19] WANG T J，WU Z Y，YANG C H，et al. Multiple mechanistic models reveal the neuroprotective effects of diterpene ginkgolides against astrocyte-mediated demyelination via the PAF-PAFR pathway[J]. Am J Chin Med，2022，50（6）：1565-1597.
[20] ZHAO H，GUO Q，LI B L，et al. The efficacy and safety of ginkgo terpene lactone preparations in the treatment of ischemic stroke：a systematic review and meta-analysis of randomized clinical trials[J/OL]. Front Pharmacol，2022，13：821937[2025-01-01]. https://doi.org/10.3389/fphar.2022.821937.