Panax Notoginseng Saponins Combined with Dual Antiplatelet Drugs Potentiates Anti-Thrombotic Effect with Alleviated Gastric Injury in A Carotid Artery Thrombosis Rat Model

Yanyan Wu; Wenting Wang; Na Kou; Mingming Wang; Lin Yang; Yu Miao; Ziwei Tang; Yimeng Gu; Yan Ma; Mei Xue; Dazhuo Shi

doi:10.1016/j.jstrokecerebrovasdis.2022.106597

Panax Notoginseng Saponins Combined with Dual Antiplatelet Drugs Potentiates Anti-Thrombotic Effect with Alleviated Gastric Injury in A Carotid Artery Thrombosis Rat Model

J Stroke Cerebrovasc Dis. 2022 Aug;31(8):106597. doi: 10.1016/j.jstrokecerebrovasdis.2022.106597. Epub 2022 Jun 15.

Authors

Yanyan Wu¹, Wenting Wang², Na Kou³, Mingming Wang³, Lin Yang³, Yu Miao³, Ziwei Tang³, Yimeng Gu³, Yan Ma⁴, Mei Xue⁵, Dazhuo Shi⁶

Affiliations

¹ Center for Cardiovascular Disease, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China; Beijing University of Chinese Medicine, Beijing 100091, China.
² Center for Cardiovascular Disease, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China; Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
³ Center for Cardiovascular Disease, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China.
⁴ Department of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Vienna General Hospital, Medical University of Vienna, Vienna 1090, Austria.
⁵ Center for Cardiovascular Disease, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China. Electronic address: meiar@126.com.
⁶ Center for Cardiovascular Disease, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China. Electronic address: shidazhuo@126.com.

PMID: 35716522
DOI: 10.1016/j.jstrokecerebrovasdis.2022.106597

Abstract

Objective: To observe the combination effects of Panax notoginseng saponins (PNS)and dual antiplatelet drugs (DAPT), and to explore the mechanism via cyclooxygenase /prostaglandin pathway.

Methods: Right carotid artery thrombosis was induced in Wistar rats by infiltration with 70% FeCl₃, and the animals were randomly divided into sham group, model group, DAPT group and PNS + DAPT group, intragastrically treated for 4 weeks. The cerebral pia mater microcirculation was observed in vivo after anesthetizing by anatomical microscope. The wet weight of carotid artery thrombosis was measured. Gastric mucosal injury was observed by hematoxylin and eosin staining. Platelet aggregation rate was detected with adenosine diphosphate -induced turbidimetry. Platelet CD62p expression was detected by flow cytometry. Concentrations of 6-Ketoprostaglandin F1 alpha, prostaglandin E₂ in gastric mucosa and thromboxane B₂, 6-Ketoprostaglandin F1 alpha, tissue plasminogen activator, plasminogen activator inhibitor, and fibrin fragment D in the plasma were measured by radioimmunoassay.

Results: PNS and DAPT increased the blood flow volume of cerebral pia mater and decreased erythrocyte aggregation and leukocyte adhesion of model rats. Compared to DAPT, PNS and DAPT further reduced the weight of carotid artery thrombosis with enhanced inhibition of platelet aggregation, increased tissue plasminogen activator levels and decreased fibrin fragment D levels. PNS and DAPT alleviated gastric injury induced by dual antiplatelet drugs and upregulated the expression of 6-Ketoprostaglandin F1 alpha in the gastric mucosa compared with DAPT.

Conclusions: PNS combined with DAPT increased anti-thrombosis effects of DAPT and mitigated DAPT-related gastric injury. The underlying mechanisms may be associated with enhanced antiplatelet aggregation and activation of the fibrinolytic system and up-regulation of 6-Ketoprostaglandin F1 alpha expression in gastric mucosa.

Keywords: Cerebrovascular diseases; Dual anti-platelet therapy; Gastric mucosa; Panax notoginseng saponins.

MeSH terms

6-Ketoprostaglandin F1 alpha
Animals
Carotid Artery Thrombosis* / drug therapy
Panax notoginseng*
Platelet Aggregation Inhibitors / pharmacology
Rats
Rats, Wistar
Saponins* / pharmacology
Thrombosis* / drug therapy
Thrombosis* / prevention & control
Tissue Plasminogen Activator / pharmacology

Substances

Platelet Aggregation Inhibitors
Saponins
6-Ketoprostaglandin F1 alpha
Tissue Plasminogen Activator