Oleanolic acid, a pentacyclic triterpenoid, induces rabbit platelet aggregation through a phospholipase C-calcium dependent signaling pathway.
Oleanolic acid (3beta-hydroxy-olea-12-en-28-oic), a pentacyclic triterpenoid, exists widely in the plant kingdom and has a wide variety of pharmacological effects such as antitumor, antifungal, insecticidal, hepatoprotective and anti-HIV activities. This paper reports that oleanolic acid induces the aggregation of rabbit platelets, a mechanism was also investigated. Oleanolic acid at concentrations of 25, 50, 100 and 200 microM induced the aggregation of washed rabbit platelets in a concentration-dependent manner. Pretreating the platelets with U73122, a phospholipase C (PLC) inhibitor, blocked the oleanolic acid induced-aggregation, whereas acetylsalicylic acid (ASA), a cyclooxygenase (COX) inhibitor, had no effect. In addition, the effect of oleanolic acid on serotonin secretion, which is a marker for dense granule secretion, was determined. Oleanolic acid induced serotonin secretion in a similar concentration-dependent manner as observed with platelet aggregation. Pretreating the platelets with U73122 blocked the oleanolic acid-induced serotonin secretion and cytosolic calcium mobilization. Overall, these results suggest that oleanolic acid can induce platelet aggregation, which may be mediated by the stimulation of PLC-mediated cytosolic calcium mobilization.
Lee
Jung-Jin
JJ
College of Pharmacy, Research Center for Bioresource and Health, Chungbuk National University, Cheongiu 361-763, Korea.
Jin
Yong-Ri
YR
Lim
Yong
Y
Yu
Ji-Yeon
JY
Kim
Tack-Joong
TJ
Yoo
Hwan-Soo
HS
Shin
Hwa-Sup
HS
Yun
Yeo-Pyo
YP
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects*; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D015394:Molecular Structure; D009828:Oleanolic Acid / Q000737:chemistry / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D011817:Rabbits; D012701:Serotonin / Q000378:metabolism; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000502:physiology*
D004791:Enzyme Inhibitors; D012701:Serotonin; D009828:Oleanolic Acid; D010738:Type C Phospholipases