Drug Design, Development and Therapy (Aug 2021)
The Synergistic Effect of Ginkgo biloba Extract 50 and Aspirin Against Platelet Aggregation
Abstract
Jia Ke,1,* Meng-Ting Li,1,* Ya-Jing Huo,1 Yan-Qiong Cheng,2 Shu-Fen Guo,1 Yang Wu,1 Lei Zhang,3 Jianpeng Ma,4 Ai-Jun Liu,2 Yan Han1 1Department of Neurology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai, People’s Republic of China; 3Department of Vascular Surgery, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 4Multiscale Research Institute of Complex Systems, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ai-Jun LiuDepartment of Pharmacology, School of Pharmacy, Second Military Medical University, 800 Xiangyin Road, Yangpu, Shanghai, 200433, People’s Republic of ChinaEmail [email protected] HanDepartment of Neurology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, 110 Ganhe Road, Hongkou, Shanghai, 200437, People’s Republic of ChinaTel +86 21 51322043Email [email protected]: We aimed to investigate potential synergistic antiplatelet effects of Ginkgo biloba extract (GBE50) in combination with aspirin using in vitro models.Methods: Arachidonic acid (AA), platelet activating factor (PAF), adenosine 5ʹ-diphosphate (ADP) and collagen were used as inducers. The antiplatelet effects of GBE50, aspirin and 1:1 combination of GBE50 and aspirin were detected by microplate method using rabbit platelets. Synergy finder 2.0 was used to analyze the synergistic antiplatelet effect. The compounds in GBE50 were identified by UPLC-Q/TOF-MS analysis and the candidate compounds were screened by TCMSP database. The targets of candidate compounds and aspirin were obtained in TCMSP, CCGs, Swiss target prediction database and drugbank. Targets involving platelet aggregation were obtained from GenCLiP database. Compound-target network was constructed and GO and KEGG enrichment analyses were performed to identify the critical biological processes and signaling pathways. The levels of thromboxane B2 (TXB2), cyclic adenosine monophosphate (cAMP) and PAF receptor (PAFR) were detected by ELISA to determine the effects of GBE50, aspirin and their combination on these pathways.Results: GBE50 combined with aspirin inhibited platelet aggregation more effectively. The combination displayed synergistic antiplatelet effects in AA-induced platelet aggregation, and additive antiplatelet effects occurred in PAF, ADP and collagen induced platelet aggregation. Seven compounds were identified as candidate compounds in GBE50. Enrichment analyses revealed that GBE50 could interfere with platelet aggregation via cAMP pathway, AA metabolism and calcium signaling pathway, and aspirin could regulate platelet aggregation through AA metabolism and platelet activation. ELISA experiments showed that GBE50 combined with aspirin could increase cAMP levels in resting platelets, and decreased the levels of TXB2 and PAFR.Conclusion: Our study indicated that GBE50 combined with aspirin could enhance the antiplatelet effects. They exerted both synergistic and additive effects in restraining platelet aggregation. The study highlighted the potential application of GBE50 as a supplementary therapy to treat thrombosis-related diseases.Keywords: Ginkgo biloba, aspirin, antiplatelet, synergistic effect, Chinese herb, arachidonic acid
