Bone-Specific Metabolism of Dietary Polyphenols in Resorptive Bone Diseases

Andrew G. Kunihiro, Paula B. Luis, Jennifer B. Frye, Wade Chew, H. H. Chow, Claus Schneider, Janet L. Funk

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number2000072
JournalMolecular Nutrition and Food Research
Volume64
Issue number14
DOIs
StatePublished - Jul 1 2020

Keywords

  • bones
  • curcumin
  • osteoclasts
  • osteoporosis
  • quercetin
  • resorptive bone diseases
  • resveratrol

ASJC Scopus subject areas

  • Biotechnology
  • Food Science

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    Kunihiro, A. G., Luis, P. B., Frye, J. B., Chew, W., Chow, H. H., Schneider, C., & Funk, J. L. (2020). Bone-Specific Metabolism of Dietary Polyphenols in Resorptive Bone Diseases. Molecular Nutrition and Food Research, 64(14), [2000072]. https://doi.org/10.1002/mnfr.202000072