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Bone‐Specific Metabolism of Dietary Polyphenols in Resorptive Bone Diseases
Author(s) -
Kunihiro Andrew G.,
Luis Paula B.,
Frye Jennifer B.,
Chew Wade,
Chow H. H.,
Schneider Claus,
Funk Janet L.
Publication year - 2020
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.202000072
Subject(s) - curcumin , chemistry , bone remodeling , glucuronide , aglycone , metabolism , bone resorption , endocrinology , resveratrol , bone disease , medicine , osteoclast , biochemistry , ovariectomized rat , pharmacology , osteoporosis , biology , in vitro , stereochemistry , glycoside , hormone
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.