Panax quinquefolius saponins combined with dual antiplatelet therapy enhanced platelet inhibition with alleviated gastric injury via regulating eicosanoids metabolism-Reference-Cited by-同舟云学术

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

Published:2023-08-18 Issue:1 Volume:23 Page:
ISSN:2662-7671
Container-title:BMC Complementary Medicine and Therapies
language:en
Short-container-title:BMC Complement Med Ther

Author:

Wang Wenting,Song Lei,Yang Lin,Li Changkun,Ma Yan,Xue Mei,Shi Dazhuo

Abstract

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.

Funder

Natural Science Foundation of Zhejiang Province

Scientific and technological innovation project of China Academy of Chinese Medical Sciences

Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine

International Sci-Technology Cooperation Project of China Academy of Chinese Medical Sciences

Publisher

Springer Science and Business Media LLC

Subject

Complementary and alternative medicine

Link

https://link.springer.com/content/pdf/10.1186/s12906-023-04112-7.pdf

Reference56 articles.

1. Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H, Caforio ALP, Crea F, Goudevenos JA, Halvorsen S, Hindricks G, Kastrati A, Lenzen MJ, Prescott E, Roffi M, Valgimigli M, Varenhorst C, Vranckx P, Widimský P. 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 Society of Cardiology (ESC). Eur Heart J. 2017;39(2018):119–77. https://doi.org/10.1093/eurheartj/ehx393.

2. Pettersen AA, Arnesen H, Seljeflot I. A brief review on high on-aspirin residual platelet reactivity. Vascul Pharmacol. 2015;67–69:6–9. https://doi.org/10.1016/j.vph.2015.03.018.

3. Angiolillo DJ, Fernandez-Ortiz A, Bernardo E, Alfonso F, Macaya C, Bass TA, Costa MA. Variability in individual responsiveness to clopidogrel: clinical implications, management, and future perspectives. J Am Coll Cardiol. 2007;49:1505–16. https://doi.org/10.1016/j.jacc.2006.11.044.

4. Bonello L, Tantry US, Marcucci R, Blindt R, Angiolillo DJ, Becker R, Bhatt DL, Cattaneo M, Collet JP, Cuisset T, Gachet C, Montalescot G, Jennings LK, Kereiakes D, Sibbing D, Trenk D, van Werkum JW, Paganelli F, Price MJ, Waksman R, Gurbel PA. Consensus and future directions on the definition of high on-treatment platelet reactivity to adenosine diphosphate. J Am Coll Cardiol. 2010;56:919–33. https://doi.org/10.1016/j.jacc.2010.04.047.

5. Gurbel PA, Bliden KP, Guyer K, Cho PW, Zaman KA, Kreutz RP, Bassi AK, Tantry US. Platelet reactivity in patients and recurrent events post-stenting: results of the PREPARE POST-STENTING Study. J Am Coll Cardiol. 2005;46:1820–6. https://doi.org/10.1016/j.jacc.2005.07.041.