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Bone-Specific Metabolism of Dietary Polyphenols in Resorptive Bone Diseases.


ABSTRACT:

Scope

Curcumin prevents bone loss in resorptive bone diseases and inhibits osteoclast formation, a key process driving bone loss. Curcumin circulates as an inactive glucuronide that can be deconjugated in situ by bone's high β-glucuronidase (GUSB) content, forming the active aglycone. Because curcumin is a common remedy for musculoskeletal disease, effects of microenvironmental changes consequent to skeletal development or disease on bone curcumin metabolism are explored.

Methods and results

Across sexual/skeletal development or between sexes in C57BL/6 mice ingesting curcumin (500 mg kg-1 ), bone curcumin metabolism and GUSB enzyme activity are unchanged, except for >twofold higher (p < 0.05) bone curcumin-glucuronide substrate levels in immature (4-6-week-old) mice. In ovariectomized (OVX) or bone metastasis-bearing female mice, bone substrate levels are also >twofold higher. Aglycone curcumin levels tend to increase proportional to substrate such that the majority of glucuronide distributing to bone is deconjugated, including OVX mice where GUSB decreases by 24% (p < 0.01). GUSB also catalyzes deconjugation of resveratrol and quercetin glucuronides by bone, and a requirement for the aglycones for anti-osteoclastogenic bioactivity, analogous to curcumin, is confirmed.

Conclusion

Dietary polyphenols circulating as glucuronides may require in situ deconjugation for bone-protective effects, a process influenced by bone microenvironmental changes.

SUBMITTER: Kunihiro AG 

PROVIDER: S-EPMC7712627 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Publications

Bone-Specific Metabolism of Dietary Polyphenols in Resorptive Bone Diseases.

Kunihiro Andrew G AG   Luis Paula B PB   Frye Jennifer B JB   Chew Wade W   Chow H H HH   Schneider Claus C   Funk Janet L JL  

Molecular nutrition & food research 20200625 14


<h4>Scope</h4>Curcumin prevents bone loss in resorptive bone diseases and inhibits osteoclast formation, a key process driving bone loss. Curcumin circulates as an inactive glucuronide that can be deconjugated in situ by bone's high β-glucuronidase (GUSB) content, forming the active aglycone. Because curcumin is a common remedy for musculoskeletal disease, effects of microenvironmental changes consequent to skeletal development or disease on bone curcumin metabolism are explored.<h4>Methods and  ...[more]

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