Beta-Glucuronidase Catalyzes Deconjugation and Activation of Curcumin-Glucuronide in Bone

Journal of Natural Products
Andrew G KunihiroJanet L Funk

Abstract

The biological basis for documented in vivo bone-protective effects of turmeric-derived curcumin is unclear since curcumin is barely detectable in serum, being rapidly conjugated to form what is thought to be an inactive glucuronide. Studies were therefore undertaken to test the postulate that antiresorptive effects of curcumin require deconjugation within bone to form the bioactive aglycone and that β-glucuronidase (GUSB), a deconjugating enzyme expressed by hematopoietic marrow cells, facilitates this site-specific transformation. Consistent with this postulate, aglycone, but not glucuronidated, curcumin inhibited RANKL-stimulated osteoclastogenesis, a key curcumin target in bone. Aglycone curcumin, expressed relative to total curcumin, was higher in bone marrow than in serum of curcumin-treated C57BL/6J mice, while remaining a minor component. Ex vivo, under conditions preventing further metabolism of the unstable aglycone, the majority of curcumin-glucuronide delivered to marrow in vivo was hydrolyzed to the aglycone, a process that was inhibited by treatment with saccharolactone, a GUSB inhibitor, or in mice having reduced (C3H/HeJ) or absent (mps/mps) GUSB activity. These findings suggest that curcumin, despite low system...Continue Reading

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Citations

Jan 22, 2020·Molecular Nutrition & Food Research·Paula B LuisClaus Schneider
Jan 26, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Der-Yen LeeMin-Tsang Hsieh
Jun 9, 2020·Molecular Nutrition & Food Research·Andrew G KunihiroJanet L Funk
Apr 21, 2021·The Journal of Nutrition·Pascale Fança-BerthonRichard B van Breemen
May 4, 2021·Molecular Nutrition & Food Research·María Ángeles Ávila-GálvezJuan Carlos Espín
May 8, 2020·Journal of Agricultural and Food Chemistry·Rebecca L EdwardsClaus Schneider
Aug 19, 2021·The Journal of Nutritional Biochemistry·Andrew G KunihiroJanet L Funk
Aug 31, 2019·Biochimie·Abdul-Musawwir Alli-OluwafuyiClaus Schneider

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