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.