Pharmacometrics of pterostilbene: preclinical pharmacokinetics and metabolism, anticancer, antiinflammatory, antioxidant and analgesic activity.
The present study evaluated the preclinical pharmacokinetics and pharmacodynamics of trans-pterostilbene, a constituent of some plants. Right jugular vein cannulated male Sprague-Dawley rats were dosed i.v. with 20 mg/kg of pterostilbene and samples were analysed by the reverse phase HPLC method. Serum AUC, serum t(1/2), urine t(1/2), Cl(total) and Vd(beta) were 17.5 +/- 6.6 microg/h/mL, 1.73 +/- 0.78 h, 17.3 +/- 5.6 h, 0.960 +/- 0.025 L/h/kg and 2.41 +/- 1.13 L/kg (mean +/- SEM), respectively. A pterostilbene glucuronidated metabolite was detected in both serum and urine. The in vitro metabolism in rat liver microsomes furthermore suggests phase II metabolism of pterostilbene. Pterostilbene demonstrated concentration-dependent anticancer activity in five cancer cell lines (1-100 microg/mL). An in vitro colitis model showed concentration-dependent suppression of PGE(2) production in the media of HT-29 cells. Antiinflammatory activity was examined by inducing inflammation in canine chondrocytes followed by treatment with pterostilbene (1-100 microg/mL). The results showed decreased levels of MMP-3, sGAG and TNF-alpha compared with control levels. Pterostilbene exhibited concentration-dependent antioxidant capacity measured by the ABTS method. Pterostilbene increased the latency period to response in both tail-flick and hot-plate analgesic tests.
Remsberg
Connie M
CM
Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University Pullman, Washington 99164-6534, USA.
Yáñez
Jaime A
JA
Ohgami
Yusuke
Y
Vega-Villa
Karina R
KR
Rimando
Agnes M
AM
Davies
Neal M
NM
D000700:Analgesics / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D000975:Antioxidants / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D019540:Area Under Curve; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D019073:HT29 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism; D015394:Molecular Structure; D010146:Pain / Q000517:prevention & control; D010147:Pain Measurement / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D013267:Stilbenes / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*
D000700:Analgesics; D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D000975:Antioxidants; D013267:Stilbenes; C107773:pterostilbene