Antiplatelet effects of Rhus verniciflua stokes heartwood and its active constituents--fisetin, butein, and sulfuretin--in rats.
Rhus verniciflua stokes (RVS) is known to promote blood circulation by preventing blood stasis, although the active ingredients and the underlying mechanism are unclear. Platelets are the primary cells that regulate circulation and contribute to the development of diverse cardiovascular diseases by aggregation and thrombosis. The study assessed the antiplatelet activity of RVS and sought to identify the active constituents. Pretreatment of washed platelets with RVS heartwood extract blunted the aggregatory response of platelets to collagen. In the subfractions, fisetin, butein, and sulfuretin were identified as effective inhibitors of platelet aggregation by collagen, thrombin, and adenosine-5'-diphosphate. Antiplatelet activities of all three compounds were concentration dependent, and fisetin had longer in vitro duration of action compared with butein or sulfuretin. Extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase activation by collagen was prevented by fisetin, whereas butein and sulfuretin failed to inhibit ERK and p38 activation was not affected by any of the compounds. Rats orally administered 100 mg/(kg·day(-1)) fisetin for 7 days were resistant to arterial thrombosis, although total extract of RVS heartwood exhibited little effect at a dose of 1000 mg/(kg·day(-1)). RVS heartwood may have cardiovascular protective activity by inhibiting platelet aggregation. The active constituents are fisetin, butein, and sulfuretin, and fisetin is orally effective against thrombosis.
1 College of Pharmacy, Dongguk University , Goyang, Gyeonggi-do, Korea.
Jun-Hyeong
JH
Lee
Mikyung
M
Kim
Kyung-Hwa
KH
Chang
Cheol Yi
CY
Hong
Chun-Soo
CS
Na
Mi-Sook
MS
Dong
Dongho
D
Lee
Moo-Yeol
MY
Lee
D000818:Animals; D001572:Benzofurans / Q000494:pharmacology* / Q000627:therapeutic use; D001792:Blood Platelets / Q000187:drug effects*; D002318:Cardiovascular Diseases / Q000378:metabolism / Q000517:prevention & control; D047188:Chalcones / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology* / Q000627:therapeutic use; D044948:Flavonols; D008297:Male; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D017207:Rats, Sprague-Dawley; D029045:Rhus / Q000737:chemistry*; D013927:Thrombosis / Q000378:metabolism / Q000517:prevention & control; D014934:Wood / Q000737:chemistry; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D001572:Benzofurans; D047188:Chalcones; D005419:Flavonoids; D044948:Flavonols; D010936:Plant Extracts; D010975:Platelet Aggregation Inhibitors; C040918:butein; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C054989:sulfuretin; C017875:fisetin
Rhus verniciflua stokes; antiplatelet; butein; fisetin; sulfuretin