Preclinical Pharmacokinetics and Pharmacodynamics and Content Analysis of Gnetol in Foodstuffs

• Published in: Phytotherapy research 2015-08, Vol.29 (8), p.1168-1179
• Main Authors: Remsberg, Connie M., Martinez, Stephanie E., Akinwumi, Bolanle C., Anderson, Hope D., Takemoto, Jody K., Sayre, Casey L., Davies, Neal M.
• Format: Article
• Language: English
• Subjects: alpha-Amylases - antagonists & inhibitors; alpha-Glucosidases; Animals; Antioxidants - pharmacology; Biological Availability; Cell Line, Tumor; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors - pharmacokinetics; Enzyme Inhibitors - pharmacokinetics; Food Analysis; Glycoside Hydrolase Inhibitors - pharmacology; gnetol; Gnetum - chemistry; Humans; Male; Membrane Proteins - antagonists & inhibitors; Mice; Pain - drug therapy; preclinical pharmacokinetics and pharmacodynamics; Rats; Rats, Sprague-Dawley; stilbene; Stilbenes - blood; Stilbenes - pharmacokinetics; Stilbenes - urine
• ISSN: 0951-418X; 1099-1573
• DOI: 10.1002/ptr.5363

Studies were undertaken to evaluate the bioavailability in rats and content analysis of gnetol in Gnetum gnemon products reported to contain gnetol and to examine the pharmacological properties of gnetol in in vitro models including anti‐inflammatory/analgesic, antidiabetic, anti‐adipogenesis, and anticancer activity. Male Sprague–Dawley rats were cannulated and dosed either intravenously with gnetol (10 mg/kg) or orally (100 mg/kg). Various methanolic extractions of G. gnemon products were quantified. Gnetol's effect on cell viability in selected cell lines with or without inflammatory stimulus was assessed. α‐Amylase and α‐glucosidase inhibition was evaluated. Cyclooxygenase (COX)‐1, COX‐2, and histone deacetylase inhibition and adipogenesis inhibition were examined. After oral and intravenous administration, gnetol was detected in both serum and urine as the parent compound and as a glucuronidated metabolite. The bioavailability of gnetol was determined to be 6%. Gnetol is rapidly glucuronidated and is excreted in urine and via nonrenal routes. Gnetol was found to exist as an aglycone and as a glycoside in G. gnemon products. Gnetol showed concentration‐dependent reductions in cell viability in cancer cell lines with greatest activity in colorectal cancer and potent COX‐1, histone deacetylase, and weak COX‐2 activities along with limited reduction in inflammation. Gnetol also possessed concentration‐dependent alpha‐amylase, alpha‐glucosidase, and adipogenesis activities. Pretreatment of mice with gnetol was able to increase the latency period to response in analgesia models. Copyright © 2015 John Wiley & Sons, Ltd.