Pharmacokinetics and metabolism of the putative cancer chemopreventive agent cyanidin-3-glucoside in mice.

OBJECTIVE

Cyanidin-3-glucoside (C3G), an anthocyanin component of fruits and berries, possesses cancer chemopreventive properties in mouse models of carcinogenesis. Its pharmacokinetics and metabolism in mice have hitherto not been studied.

METHODS

C57BL6J mice received C3G by either gavage at 500 mg/kg or tail vein injection at 1 mg/kg. Blood, urine, bile and heart, lung, kidney, liver, prostate, brain and gastrointestinal (gi) mucosal tissues were obtained up to 2 h after administration. Levels of C3G and its anthocyanin metabolites were determined by HPLC with visible detection. Metabolites were identified by LC/MS/MS.

RESULTS

After oral administration peak concentrations of anthocyanins occurred within 30 min after administration. Levels were highest in the urine and gi mucosa. In the gi mucosa and liver the predominant flavonoid species after oral administration was C3G, whilst after iv dosing the majority of anthocyanins was C3G metabolites. After oral or iv administration, C3G half-lives in the different biofluids and tissues ranged from 0.7 to 1.8 h and 0.3 to 0.7 h, respectively. Systemic bioavailabilities for parent C3G and total anthocyanins were 1.7 and 3.3%, respectively. The major metabolites of C3G were products of methylation and glucuronidation. Cyanidin was a minor metabolite in the gut.

CONCLUSIONS

C3G and its metabolites were recovered from murine tissues which may be targets for cancer chemopreventive intervention. Anthocyanin levels achieved in the gi mucosa, prostate and the kidneys were of an order of magnitude consistent with pharmacological activity.