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

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...