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Sabolovic, N. et al.

Nicole Sabolovic, Tony Heurtaux, Anne-Claude Humbert, Stéphanie Krisa, Jacques Magdalou,

cis- and trans-Resveratrol are glucuronidated in rat brain, olfactory mucosa and cultured astrocytes.

BACKGROUND/AIMS: Glucuronidation of cis- and trans-resveratrol (3,5,4'-trihydroxy-trans-stilbene), which is a naturally occurring phytoalexin known to exert a number of beneficial health effects, was investigated in rat brain, cultured astrocytes and olfactory mucosa. METHODS: The isomers were incubated with tissue homogenates, microsomes, or rat liver recombinant UDP-glucuronosyltransferases in the presence of UDP-glucuronic acid. The glucuronides were separated by HPLC and quantitated. Astrocytes were exposed to lipopolysaccharide to promote inflammatory conditions. RESULTS: All tissues were able to form resveratrol glucuronides although at a lower extent, when compared to the liver. The reaction was stereo- and regioselective. In brain tissue, trans-resveratrol 3-O-glucuronide was mainly formed, whereas the cis-isomer was glucuronidated at a lower rate on that position. No 4'-O-glucuronide was detected in brain. In olfactory mucosa homogenates, the cis 3-O-glucuronide was mainly formed, whereas the trans-isomer was glucuronidated only on the 3-position. In astrocytes, 3-O-glucuronides of the cis- and trans-resveratrol were only detected. The rat recombinant UGT1A6 and UGT2B1 isoforms were able to glucuronidate cis- and trans-resveratrol. Finally, in inflammatory conditions, trans-resveratrol glucuronidation was enhanced in astrocytes. CONCLUSION: Brain tissues are effective in the glucuronidation of resveratrol isomers. This metabolism pathway is likely to modulate the concentration of these biologically active substances.[1]

References

cis- and trans-Resveratrol are glucuronidated in rat brain, olfactory mucosa and cultured astrocytes. Sabolovic, N., Heurtaux, T., Humbert, A.C., Krisa, S., Magdalou, J. Pharmacology (2007) [Pubmed]

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