Panax Quinquefolius Saponins Combined with Dual Antiplatelet Therapy Enhanced Platelet Inhibition with Alleviated Gastric Injury Via Regulating Eicosanoids Metabolism

Overview

Journal BMC Complement Med Ther

Publisher Biomed Central

Specialty Rehabilitation Medicine

Date 2023 Aug 18

PMID 37596586

Authors

Wenting Wang

Lei Song

Lin Yang

Changkun Li

Yan Ma

Mei Xue

Dazhuo Shi

Affiliations

Soon will be listed here.

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) I (potent inhibitors for platelet adhesion and aggregation) while markedly decreased thromboxane (TX) A (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 (PGE, PGD and PGI) 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/PGI synthesis while suppression of AA/TXA metabolism. PQS attenuated DAPT-induced gastric injury, which was mechanistically linked to increased mucosal PG production.

Citing Articles

Protective Effect of Pentoxifylline on the Development of Acute Gastric Mucosal Injury in a Model of LPS-Induced Sepsis.

Paredes S, Hernandez-Cortes J, Falahat F, Rancan L, Arias-Diaz J, Vara E Antioxidants (Basel). 2025; 13(12.

PMID: 39765810 PMC: 11673027. DOI: 10.3390/antiox13121481.

Oxylipins as therapeutic indicators of herbal medicines in cardiovascular diseases: a review.

Li M, He M, Sun M, Li Y, Li M, Jiang X Front Pharmacol. 2025; 15:1454348.

PMID: 39749208 PMC: 11693728. DOI: 10.3389/fphar.2024.1454348.

Panax quinquefolius saponins and panax notoginseng saponins attenuate myocardial hypoxia-reoxygenation injury by reducing excessive mitophagy.

Xia J, Chen C, Sun Y, Li S, Li Y, Cheng B Cell Biochem Biophys. 2024; 82(2):1179-1191.

PMID: 38713401 DOI: 10.1007/s12013-024-01267-z.

References

Uotani T, Sugimoto M, Nishino M, Kodaira C, Yamade M, Sahara S . Ability of rabeprazole to prevent gastric mucosal damage from clopidogrel and low doses of aspirin depends on CYP2C19 genotype. Clin Gastroenterol Hepatol. 2012; 10(8):879-885.e2. DOI: 10.1016/j.cgh.2012.04.016. View

Karmazyn M, Moey M, Gan X . Therapeutic potential of ginseng in the management of cardiovascular disorders. Drugs. 2011; 71(15):1989-2008. DOI: 10.2165/11594300-000000000-00000. View

Krotz F, Riexinger T, Buerkle M, Nithipatikom K, Gloe T, Sohn H . Membrane-potential-dependent inhibition of platelet adhesion to endothelial cells by epoxyeicosatrienoic acids. Arterioscler Thromb Vasc Biol. 2004; 24(3):595-600. DOI: 10.1161/01.ATV.0000116219.09040.8c. View

Bonello L, Tantry U, Marcucci R, Blindt R, Angiolillo D, Becker R . Consensus and future directions on the definition of high on-treatment platelet reactivity to adenosine diphosphate. J Am Coll Cardiol. 2010; 56(12):919-33. DOI: 10.1016/j.jacc.2010.04.047. View

Alkhamis T, Beissinger R, Chediak J . Artificial surface effect on red blood cells and platelets in laminar shear flow. Blood. 1990; 75(7):1568-75. View

Wang M, Xue M, Miao Y, Kou N, Xu Y, Yang L . Panax quinquefolium saponin combined with dual antiplatelet drugs inhibits platelet adhesion to injured HUVECs via PI3K/AKT and COX pathways. J Ethnopharmacol. 2016; 192:10-19. DOI: 10.1016/j.jep.2016.07.015. View

Adatia K, Farag M, Gue Y, Srinivasan M, Gorog D . Relationship of Platelet Reactivity and Inflammatory Markers to Recurrent Adverse Events in Patients with ST-Elevation Myocardial Infarction. Thromb Haemost. 2019; 119(11):1785-1794. DOI: 10.1055/s-0039-1695007. View

Guo M, Wang P, Du J, Fu C, Yang Q, Gao Z . Xinyue Capsule in patients with stable coronary artery disease after percutaneous coronary intervention: a multicenter, randomized, placebo-controlled trial. Pharmacol Res. 2020; 158:104883. DOI: 10.1016/j.phrs.2020.104883. View

Wurtz M, Grove E . Proton Pump Inhibitors in Cardiovascular Disease: Drug Interactions with Antiplatelet Drugs. Adv Exp Med Biol. 2016; 906:325-350. DOI: 10.1007/5584_2016_124. View

10.

Patrono C, Garcia Rodriguez L, Landolfi R, Baigent C . Low-dose aspirin for the prevention of atherothrombosis. N Engl J Med. 2005; 353(22):2373-83. DOI: 10.1056/NEJMra052717. View

11.

Tacconelli S, Patrignani P . Inside epoxyeicosatrienoic acids and cardiovascular disease. Front Pharmacol. 2014; 5:239. PMC: 4226225. DOI: 10.3389/fphar.2014.00239. View

12.

Yamada M, Kita Y, Kohira T, Yoshida K, Hamano F, Tokuoka S . A comprehensive quantification method for eicosanoids and related compounds by using liquid chromatography/mass spectrometry with high speed continuous ionization polarity switching. J Chromatogr B Analyt Technol Biomed Life Sci. 2015; 995-996:74-84. DOI: 10.1016/j.jchromb.2015.05.015. View

13.

Imig J . Eicosanoid blood vessel regulation in physiological and pathological states. Clin Sci (Lond). 2020; 134(20):2707-2727. DOI: 10.1042/CS20191209. View

14.

Angiolillo D, Fernandez-Ortiz A, Bernardo E, Alfonso F, Macaya C, Bass T . Variability in individual responsiveness to clopidogrel: clinical implications, management, and future perspectives. J Am Coll Cardiol. 2007; 49(14):1505-16. DOI: 10.1016/j.jacc.2006.11.044. View

15.

Gargiulo G, Esposito G, Avvedimento M, Nagler M, Minuz P, Campo G . Cangrelor, Tirofiban, and Chewed or Standard Prasugrel Regimens in Patients With ST-Segment-Elevation Myocardial Infarction: Primary Results of the FABOLUS-FASTER Trial. Circulation. 2020; 142(5):441-454. PMC: 7392586. DOI: 10.1161/CIRCULATIONAHA.120.046928. View

16.

Ibanez B, James S, Agewall S, Antunes M, Bucciarelli-Ducci C, Bueno H . 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European.... Eur Heart J. 2017; 39(2):119-177. DOI: 10.1093/eurheartj/ehx393. View

17.

Dennis E, Norris P . Eicosanoid storm in infection and inflammation. Nat Rev Immunol. 2015; 15(8):511-23. PMC: 4606863. DOI: 10.1038/nri3859. View

18.

Wallace J . Prostaglandins, NSAIDs, and gastric mucosal protection: why doesn't the stomach digest itself?. Physiol Rev. 2008; 88(4):1547-65. DOI: 10.1152/physrev.00004.2008. View

19.

Quehenberger O, Dennis E . The human plasma lipidome. N Engl J Med. 2011; 365(19):1812-23. PMC: 3412394. DOI: 10.1056/NEJMra1104901. View

20.

Bhatt D, Scheiman J, Abraham N, Antman E, Chan F, Furberg C . ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents. Circulation. 2008; 118(18):1894-909. DOI: 10.1161/CIRCULATIONAHA.108.191087. View