Inhibitory effect of Andrographis paniculata extract and its active diterpenoids on platelet aggregation.
Andrographis paniculata has been widely used for the prevention and treatment of common cold especially in Asia and Scandinavia. The three active diterpenoids from this plant, including aqueous plant extracts, were investigated for the inhibitory effect on platelet aggregation in vitro. The results indicated that andrographolide (AP(1)) and 14-deoxy-11,12-didehydroandrographolide (AP(3)) significantly inhibited thrombin-induced platelet aggregation in a concentration-(1-100 microM) and time-dependent manner while neoandrographolide (AP(4)) had little or no activity. AP(3) exhibited higher antiplatelet activity than AP(1) with IC(50) values ranging from 10 to 50 microM. The inhibitory mechanism of AP(1) and AP(3) on platelet aggregation was also evaluated and the results indicated that the inhibition of extracellular signal-regulated kinase1/2 (ERK1/2) pathway may contribute to antiplatelet activity of these two compounds. In addition, standardized aqueous extracts of A. paniculata containing different amounts of AP(3) inhibited thrombin-induced aggregation to different degrees. The extracts significantly decreased platelet aggregation in a concentration-(10-100 microg/ml) and time-dependent manner. However, the extract with high level of AP(3) (Extract B) (IC(50) values=50-75 microg/ml) showed less inhibitory activity against thrombin than the extract with lower level of AP(3) (Extract A) (IC(50) values=25-50 microg/ml). These results indicate that the standardized A. paniculata extract may contain other antiplatelet compounds rather than AP(1) and AP(3), which contribute to high antiplatelet activity. Therefore, the consumption of A. paniculata products may help to prevent or treat some cardiovascular disorders i.e. thrombosis; however, it should be used with caution by patients with bleeding disorders.
Thisoda
Piengpen
P
Toxicology Graduate Programme, Faculty of Science, Mahidol University, Rama VI Road, Bangkok 10400, Thailand; Laboratory of Pharmacology, Chulabhorn Research Institute, Vipavadee-Rangsit Highway, Laksi, Bangkok 10210, Thailand.
Rangkadilok
Nuchanart
N
Pholphana
Nanthanit
N
Worasuttayangkurn
Luksamee
L
Ruchirawat
Somsak
S
Satayavivad
Jutamaad
J
D035685:Andrographis / Q000737:chemistry*; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology; D004224:Diterpenes / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005960:Glucosides / Q000737:chemistry / Q000494:pharmacology*; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D008297:Male; D010766:Phosphorylation; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013764:Tetrahydronaphthalenes / Q000737:chemistry / Q000494:pharmacology*
C495626:14-deoxy-11,12-didehydroandrographolide; D004224:Diterpenes; D005960:Glucosides; D007202:Indicators and Reagents; D010936:Plant Extracts; D013764:Tetrahydronaphthalenes; C030419:andrographolide; D048049:Extracellular Signal-Regulated MAP Kinases; C082497:neoandrographolide