Panax quinquefolius saponins combined with dual antiplatelet therapy enhanced platelet inhibition with alleviated gastric injury via regulating eicosanoids metabolism

Abstract Background Panax quinquefolius saponin (PQS) was shown beneficial against platelet adhesion and for gastroprotection. This study aimed to investigate the integrated efficacy of PQS with dual antiplatelet therapy (DAPT) on platelet aggregation, myocardial infarction (MI) expansion and gastri...

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Main Authors: Wenting Wang, Lei Song, Lin Yang, Changkun Li, Yan Ma, Mei Xue, Dazhuo Shi
Format: Article
Language:English
Published: BMC 2023-08-01
Series:BMC Complementary Medicine and Therapies
Subjects:
Online Access:https://doi.org/10.1186/s12906-023-04112-7
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author Wenting Wang
Lei Song
Lin Yang
Changkun Li
Yan Ma
Mei Xue
Dazhuo Shi
author_facet Wenting Wang
Lei Song
Lin Yang
Changkun Li
Yan Ma
Mei Xue
Dazhuo Shi
author_sort Wenting Wang
collection DOAJ
description Abstract Background Panax quinquefolius saponin (PQS) was shown beneficial against platelet adhesion and for gastroprotection. This study aimed to investigate the integrated efficacy of PQS with dual antiplatelet therapy (DAPT) on platelet aggregation, myocardial infarction (MI) expansion and gastric injury in a rat model of acute MI (AMI) and to explore the mechanism regarding arachidonic acid (AA)-derived eicosanoids metabolism. Methods Wistar rats were subjected to left coronary artery occlusion to induce AMI model followed by treatment with DAPT, PQS or the combined therapy. Platelet aggregation was measured by light transmission aggregometry. Infarct size, myocardial histopathology was evaluated by TTC and H&E staining, respectively. Gastric mucosal injury was examined by scanning electron microscope (SEM). A comprehensive eicosanoids profile in plasma and gastric mucosa was characterized by liquid chromatography-mass spectrometer-based lipidomic analysis. Results PQS+DAPT further decreased platelet aggregation, lessened infarction and attenuated cardiac injury compared with DAPT. Plasma lipidomic analysis revealed significantly increased synthesis of epoxyeicosatrienoic acid (EET) and prostaglandin (PG) I2 (potent inhibitors for platelet adhesion and aggregation) while markedly decreased thromboxane (TX) A2 (an agonist for platelet activation and thrombosis) by PQS+DAPT, relative to DAPT. DAPT induced overt gastric mucosal damage, which was attenuated by PQS co-administration. Mucosal gastroprotective PGs (PGE2, PGD2 and PGI2) were consistently increased after supplementation of PQS+DAPT. Conclusions Collectively, PQS+DAPT showed synergistic effect in platelet inhibition with ameliorated MI expansion partially through upregulation of AA/EET and AA/PGI2 synthesis while suppression of AA/TXA2 metabolism. PQS attenuated DAPT-induced gastric injury, which was mechanistically linked to increased mucosal PG production.
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spelling doaj.art-bca46420e5fe4df2bbcb597400585d072023-11-26T12:19:42ZengBMCBMC Complementary Medicine and Therapies2662-76712023-08-0123111410.1186/s12906-023-04112-7Panax quinquefolius saponins combined with dual antiplatelet therapy enhanced platelet inhibition with alleviated gastric injury via regulating eicosanoids metabolismWenting Wang0Lei Song1Lin Yang2Changkun Li3Yan Ma4Mei Xue5Dazhuo Shi6National Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, China Academy of Chinese Medical SciencesNational Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, China Academy of Chinese Medical SciencesNational Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, China Academy of Chinese Medical SciencesShimadzu (China) Co., LTD Beijing BranchDepartment of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology & Immunology, Vienna General Hospital, Medical University of ViennaNational Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, China Academy of Chinese Medical SciencesNational Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, China Academy of Chinese Medical SciencesAbstract Background Panax quinquefolius saponin (PQS) was shown beneficial against platelet adhesion and for gastroprotection. This study aimed to investigate the integrated efficacy of PQS with dual antiplatelet therapy (DAPT) on platelet aggregation, myocardial infarction (MI) expansion and gastric injury in a rat model of acute MI (AMI) and to explore the mechanism regarding arachidonic acid (AA)-derived eicosanoids metabolism. Methods Wistar rats were subjected to left coronary artery occlusion to induce AMI model followed by treatment with DAPT, PQS or the combined therapy. Platelet aggregation was measured by light transmission aggregometry. Infarct size, myocardial histopathology was evaluated by TTC and H&E staining, respectively. Gastric mucosal injury was examined by scanning electron microscope (SEM). A comprehensive eicosanoids profile in plasma and gastric mucosa was characterized by liquid chromatography-mass spectrometer-based lipidomic analysis. Results PQS+DAPT further decreased platelet aggregation, lessened infarction and attenuated cardiac injury compared with DAPT. Plasma lipidomic analysis revealed significantly increased synthesis of epoxyeicosatrienoic acid (EET) and prostaglandin (PG) I2 (potent inhibitors for platelet adhesion and aggregation) while markedly decreased thromboxane (TX) A2 (an agonist for platelet activation and thrombosis) by PQS+DAPT, relative to DAPT. DAPT induced overt gastric mucosal damage, which was attenuated by PQS co-administration. Mucosal gastroprotective PGs (PGE2, PGD2 and PGI2) were consistently increased after supplementation of PQS+DAPT. Conclusions Collectively, PQS+DAPT showed synergistic effect in platelet inhibition with ameliorated MI expansion partially through upregulation of AA/EET and AA/PGI2 synthesis while suppression of AA/TXA2 metabolism. PQS attenuated DAPT-induced gastric injury, which was mechanistically linked to increased mucosal PG production.https://doi.org/10.1186/s12906-023-04112-7Panax quinquefolius saponinsDual antiplatelet therapyPlatelet inhibitionGastric injuryLipidomicsEicosanoids
spellingShingle Wenting Wang
Lei Song
Lin Yang
Changkun Li
Yan Ma
Mei Xue
Dazhuo Shi
Panax quinquefolius saponins combined with dual antiplatelet therapy enhanced platelet inhibition with alleviated gastric injury via regulating eicosanoids metabolism
BMC Complementary Medicine and Therapies
Panax quinquefolius saponins
Dual antiplatelet therapy
Platelet inhibition
Gastric injury
Lipidomics
Eicosanoids
title Panax quinquefolius saponins combined with dual antiplatelet therapy enhanced platelet inhibition with alleviated gastric injury via regulating eicosanoids metabolism
title_full Panax quinquefolius saponins combined with dual antiplatelet therapy enhanced platelet inhibition with alleviated gastric injury via regulating eicosanoids metabolism
title_fullStr Panax quinquefolius saponins combined with dual antiplatelet therapy enhanced platelet inhibition with alleviated gastric injury via regulating eicosanoids metabolism
title_full_unstemmed Panax quinquefolius saponins combined with dual antiplatelet therapy enhanced platelet inhibition with alleviated gastric injury via regulating eicosanoids metabolism
title_short Panax quinquefolius saponins combined with dual antiplatelet therapy enhanced platelet inhibition with alleviated gastric injury via regulating eicosanoids metabolism
title_sort panax quinquefolius saponins combined with dual antiplatelet therapy enhanced platelet inhibition with alleviated gastric injury via regulating eicosanoids metabolism
topic Panax quinquefolius saponins
Dual antiplatelet therapy
Platelet inhibition
Gastric injury
Lipidomics
Eicosanoids
url https://doi.org/10.1186/s12906-023-04112-7
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