@article{1d6191d9bc9a4c2cb00061158079aa69,
title = "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.",
keywords = "bones, curcumin, osteoclasts, osteoporosis, quercetin, resorptive bone diseases, resveratrol",
author = "Kunihiro, {Andrew G.} and Luis, {Paula B.} and Frye, {Jennifer B.} and Wade Chew and Chow, {H. H.} and Claus Schneider and Funk, {Janet L.}",
note = "Funding Information: This work was supported by the National Cancer Institute (NCI), the National Center for Complementary and Integrative Health (NCCIH), and the Office of Dietary Supplements (ODS) at the National Institutes of Health (NIH) (R01CA174926 and R34AT007837 to J.L.F., R01AT006896 to C.S., and F31AT009938 to A.G.K.); the United States Department of Agriculture (2014‐38420‐21799 National Needs Fellowship to A.G.K.); and the American Heart Association (16POST27250138 postdoctoral fellowship to P.B.L.). Mass spectrometric analyses were performed in part through Vanderbilt University Medical Center's Digestive Disease Research Center supported by NIH grant P30DK058404 Core Scholarship. Pharmacokinetic analyses were performed in part through the University of Arizona Cancer Center's Analytical Chemistry Shared Resource supported by NCI Cancer Center Support Grant P30CA023074. Funding Information: This work was supported by the National Cancer Institute (NCI), the National Center for Complementary and Integrative Health (NCCIH), and the Office of Dietary Supplements (ODS) at the National Institutes of Health (NIH) (R01CA174926 and R34AT007837 to J.L.F., R01AT006896 to C.S., and F31AT009938 to A.G.K.); the United States Department of Agriculture (2014-38420-21799 National Needs Fellowship to A.G.K.); and the American Heart Association (16POST27250138 postdoctoral fellowship to P.B.L.). Mass spectrometric analyses were performed in part through Vanderbilt University Medical Center's Digestive Disease Research Center supported by NIH grant P30DK058404 Core Scholarship. Pharmacokinetic analyses were performed in part through the University of Arizona Cancer Center's Analytical Chemistry Shared Resource supported by NCI Cancer Center Support Grant P30CA023074. Publisher Copyright: {\textcopyright} 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim",
year = "2020",
month = jul,
day = "1",
doi = "10.1002/mnfr.202000072",
language = "English (US)",
volume = "64",
journal = "Die Nahrung",
issn = "1613-4125",
publisher = "Wiley-VCH Verlag",
number = "14",
}