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Planta Med 2020; 86(10): 696-707
DOI: 10.1055/a-1146-2861
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Ginkgo biloba and Its Constituent 6-hydroxykynurenic-acid as well as Its Proanthocyanidins Exert Neurorestorative Effects against Cerebral Ischemia

Jianbiao Yao   *
1   College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China
,
Hongxiang Qiao   *
2   Zhejiang CONBA Pharmaceutical, Hangzhou, China
,
Zhuming Jin
2   Zhejiang CONBA Pharmaceutical, Hangzhou, China
,
Ruwei Wang
2   Zhejiang CONBA Pharmaceutical, Hangzhou, China
3   Zhejiang Provincial Key Laboratory of Traditional Chinese Medicine Pharmaceutical Technology, Hangzhou, China
,
Haibo Huang
2   Zhejiang CONBA Pharmaceutical, Hangzhou, China
,
Ling Fang
2   Zhejiang CONBA Pharmaceutical, Hangzhou, China
,
Yan Chen
4   Department of Neurosurgery, Sun Yat-sen University, First Affiliated Hospital, Guangzhou City, Guangdong Province, China
,
Khalid Tai
5   Department of Neurology, University Medical Center Goettingen, Goettingen, Germany
,
Yan Chen
6   Zhejiang University of Technology, Hangzhou, China
,
Thorsten Roland Doeppner   **
5   Department of Neurology, University Medical Center Goettingen, Goettingen, Germany
,
Zhong Chen   **
1   College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China
,
Kenny Kuchta   **
7   Clinic for Gastroenterology and Gastrointestinal Oncology, University Medical Center Goettingen, Goettingen, Germany
› Author AffiliationsSupported by: The National Key Research and Development Program of China Grant No. 2017YFD0601301
Further Information

Publication History

received 03 April 2019
revised 18 March 2020

accepted 23 March 2020

Publication Date:
15 May 2020 (online)

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Abstract

Neuroprotective effects against cerebral ischemia/reperfusion (I/R) injury by Ginkgo biloba leaves are commonly attributed to the antioxidant activity of its proanthocyanidins. Furthermore, preliminary experiments identified 6-hydroxykynurenic acid (6-HKA) as a major contributor to this effect of extract of G. biloba leaves (EGb) prepared according to the Chinese Pharmacopoeia (ChP). In order to elucidate the specific contribution of both proanthocyanidins and 6-HKA to the overall neurorestorative effects of this extract according to ChP, EGb ChP was separated into pure 6-HKA and a newly developed Ginkgo proanthocyanidin extract (GPE), enriched in proanthocyanidins but not containing 6-HKA. Male Sprague-Dawley rats were divided into the groups: sham: 8; model (placebo): 25; GPE 80 mg/kg: 13; GPE 40 mg/kg: 13; GPE 20 mg/kg: 16; grape seed extract (negative control) 40 mg/kg: 18; nimodipine (positive control) 2 mg/kg: 8. All non-sham animals were subjected to cerebral I/R injury by occluding the middle cerebral artery with a nylon suture that was removed after 2 h of ischemia to establish reperfusion. For comparison, a parallel series of experiments were performed with 6-HKA. In these in vivo experiments, neurological dysfunctions were reduced by both GPE and 6-HKA, and both average infarct size and concentrations of malondialdehyde (MDA) and super oxide dismutase (SOD) were significantly ameliorated as compared to the model group. This data, therefore, demonstrates that the neuroprotective effects of EGb cannot be explained by a purely chemical antioxidative effect alone as has been previously proposed, especially with regards to the proanthocyanidins. A pharmacological neurorestorative effect of EGb on neurons and brain tissue itself seems to be a much more straightforward explanation for the presented observations. This effect is most likely explained by the synergistic action of both its numerous phenolic constituents (GPE) and 6-hydroxykynurenic acid (6-HKA), which could be identified as one major contributor to the observed activity.

Key words

Ginkgo biloba - Ginkgoaceae - cerebral ischemia - proanthocyanidins - 6-hydroxykynurenic acid (6-HKA) - neuroprotection

* Authors contributed equally to the work.


** Authors contributed equally to the work.


 

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