Selective Inhibition of P2Y 1 and P2Y 12 Receptor Signal Pathways in Platelet Aggregation in Transgenic Cell Lines and Rats by Potassium 2-(1-Hydroxypentyl)-Benzoate, Puerarin and Salvianolic Acid B.

Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 101473265 Publication Model: Print Cited Medium: Internet ISSN: 1755-5949 (Electronic) Linking ISSN: 17555930 NLM ISO Abbreviation: CNS Neurosci Ther Subsets: MEDLINE

Original Publication: Oxford, UK : Wiley-Blackwell, c2008-

Benzofurans*/pharmacology ; Isoflavones*/pharmacology ; Receptors, Purinergic P2Y1*/metabolism ; Receptors, Purinergic P2Y1*/drug effects ; Receptors, Purinergic P2Y12*/metabolism ; Platelet Aggregation*/drug effects ; Signal Transduction*/drug effects; Animals ; Humans ; Rats ; HEK293 Cells ; Male ; Rats, Sprague-Dawley ; Cyclic AMP/metabolism ; Platelet Aggregation Inhibitors/pharmacology ; Adenosine Diphosphate/pharmacology ; Adenosine Diphosphate/analogs & derivatives ; Thionucleotides/pharmacology ; Calcium/metabolism ; Purinergic P2Y Receptor Antagonists/pharmacology ; Depsides

Aim: Potassium 2-(1-hydroxypentyl)-benzoate (dl-PHPB), puerarin and salvianolic acid B are three natural products or derivatives that can inhibit platelet aggregation. However, the mechanisms of dl-PHPB, puerarin and salvianolic acid B to inhibit platelet aggregation are still not clear.
Method: Here, 2-methylthioadenosine diphosphate (2-MeSADP) was used as an inducer to confirm the effects of three drugs on platelet aggregation and illustrate the corresponding mechanisms.
Result: The results indicated that dl-PHPB, puerarin and salvianolic acid B significantly inhibited platelet aggregation both in vivo and in vitro. In addition, the content of IP 3 , cAMP and intracellular [Ca ²⁺ ] i were measured in HEK293 cell lines overexpressing P2Y 1 and P2Y 12 . Dl-PHPB and puerarin could obviously reduce 2-MeSADP-induced IP 3 increase, but salvianolic acid B showed no effects. Unlike dl-PHPB and puerarin, which had no effects on 2-MeSADP-induced cAMP decrease, salvianolic acid B significantly reversed the reduction of cAMP. Both dl-PHPB and puerarin could decrease the enhanced intracellular [Ca ²⁺ ] i induced by 2-MeSADP; however, salvianolic acid B showed no effect on intracellular [Ca ²⁺ ] i elevation.
Conclusion: These results suggested that dl-PHPB and puerarin inhibited platelet aggregation via targeting at P2Y 1 receptor and P2Y 1 -Gq-IP 3 -Ca ²⁺ signal pathway. Differently, salvianolic acid B inhibited platelet aggregation via targeting at P2Y 12 receptor and via Gi-AC-cAMP signal pathway.
(© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Biochem Pharmacol. 2000 Nov 15;60(10):1475-83. (PMID: 11020449)
Lancet. 1996 Nov 16;348(9038):1329-39. (PMID: 8918275)
Chin J Integr Med. 2018 Feb;24(2):103-108. (PMID: 29067595)
BMJ. 1994 Jan 8;308(6921):81-106. (PMID: 8298418)
Evid Based Complement Alternat Med. 2022 Mar 26;2022:7941039. (PMID: 35378909)
Nat Rev Drug Discov. 2006 Mar;5(3):247-64. (PMID: 16518376)
J Clin Invest. 1999 Dec;104(12):1731-7. (PMID: 10606627)
Am J Chin Med. 2006;34(6):1037-45. (PMID: 17163592)
Thromb Res. 2014 Oct;134(4):866-76. (PMID: 25077998)
Platelets. 2003 Feb;14(1):15-20. (PMID: 12623443)
Biomed Res Int. 2016;2016:2532371. (PMID: 27069920)
J Med Chem. 2020 Dec 24;63(24):15752-15772. (PMID: 33307675)
Gene. 1996 Jun 1;171(2):295-7. (PMID: 8666290)
Neurosci Lett. 2017 Mar 16;643:45-51. (PMID: 28192195)
FEBS Lett. 1997 Feb 10;403(1):26-30. (PMID: 9038354)
J Chromatogr B Analyt Technol Biomed Life Sci. 2017 Nov 15;1068-1069:253-260. (PMID: 29132906)
Stroke. 2000 Jun;31(6):1240-9. (PMID: 10835439)
Thromb Haemost. 1999 Mar;81(3):373-7. (PMID: 10102463)
Food Chem. 2017 Mar 15;219:93-101. (PMID: 27765264)
Stroke. 1999 Mar;30(3):546-9. (PMID: 10066850)
Thromb Res. 2000 Mar 15;97(6):441-9. (PMID: 10704653)
Clin Haematol. 1978 Oct;7(3):523-39. (PMID: 363326)
Thromb Res. 2015 Jan;135(1):137-45. (PMID: 25466843)
Naunyn Schmiedebergs Arch Pharmacol. 2015 Sep;388(9):983-90. (PMID: 25787305)
Eur J Pharmacol. 2001 Feb 2;412(3):213-21. (PMID: 11166284)
Br J Haematol. 2000 Dec;111(3):733-44. (PMID: 11122132)
Semin Thromb Hemost. 2005 Apr;31(2):174-83. (PMID: 15852221)
Chin Med J (Engl). 2013;126(18):3405-10. (PMID: 24034079)
Mol Pharmacol. 1996 Nov;50(5):1323-9. (PMID: 8913364)
Yao Xue Xue Bao. 1995;30(10):741-4. (PMID: 8701729)
Arterioscler Thromb. 1992 Apr;12(4):430-6. (PMID: 1558834)
Brain Res. 2017 Apr 15;1661:37-48. (PMID: 28214521)
Biochem Pharmacol. 2014 Nov 15;92(2):251-65. (PMID: 25268843)
J Pharmacol Exp Ther. 2006 Jun;317(3):973-9. (PMID: 16527903)
Biochem J. 1990 Feb 1;265(3):675-80. (PMID: 2306207)
Inflammation. 2016 Aug;39(4):1503-13. (PMID: 27255374)
Biochim Biophys Acta. 2009 Feb;1793(2):325-34. (PMID: 18973777)
Biochem Pharmacol. 2004 Nov 15;68(10):1995-2002. (PMID: 15476670)
Stroke. 1994 Feb;25(2):278-81. (PMID: 8303731)
Clin Hemorheol Microcirc. 2004;31(2):97-103. (PMID: 15310944)

2021-I2M-1-028-1 Chinese Academy of Medical Sciences Initiative for Innovative Medicine; BZ0150 Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study; 821QN260 Natural Science Foundation of Hainan Province; QCXM202023 Project of Hainan Association for Science and Technology of Youth Science and Talents

Keywords: P2Y1; P2Y12; platelets aggregation; potassium 2‐(1‐hydroxypentyl)‐benzoate; puerarin; salvianolic acid B

C1GQ844199 (salvianolic acid B)
0 (Benzofurans)
0 (Isoflavones)
0 (Receptors, Purinergic P2Y1)
Z9W8997416 (puerarin)
0 (Receptors, Purinergic P2Y12)
E0399OZS9N (Cyclic AMP)
0 (Platelet Aggregation Inhibitors)
34983-48-7 (methylthio-ADP)
61D2G4IYVH (Adenosine Diphosphate)
0 (Thionucleotides)
SY7Q814VUP (Calcium)
0 (Purinergic P2Y Receptor Antagonists)
0 (Depsides)

Date Created: 20241120 Date Completed: 20241120 Latest Revision: 20241123

20250114

PMC11576485

10.1111/cns.70089

39563013