Bone-Specific Metabolism of Dietary Polyphenols in Resorptive Bone Diseases
© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:64 |
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| Enthalten in: |
Molecular nutrition & food research - 64(2020), 14 vom: 16. Juli, Seite e2000072 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kunihiro, Andrew G [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 26.07.2021 Date Revised 10.11.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/mnfr.202000072 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM310863287 |
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| 100 | 1 | |a Kunihiro, Andrew G |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Bone-Specific Metabolism of Dietary Polyphenols in Resorptive Bone Diseases |
| 264 | 1 | |c 2020 | |
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| 500 | |a Date Completed 26.07.2021 | ||
| 500 | |a Date Revised 10.11.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a CONCLUSION: Dietary polyphenols circulating as glucuronides may require in situ deconjugation for bone-protective effects, a process influenced by bone microenvironmental changes | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, U.S. Gov't, Non-P.H.S. | |
| 650 | 4 | |a bones | |
| 650 | 4 | |a curcumin | |
| 650 | 4 | |a osteoclasts | |
| 650 | 4 | |a osteoporosis | |
| 650 | 4 | |a quercetin | |
| 650 | 4 | |a resorptive bone diseases | |
| 650 | 4 | |a resveratrol | |
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| 700 | 1 | |a Luis, Paula B |e verfasserin |4 aut | |
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| 700 | 1 | |a Chew, Wade |e verfasserin |4 aut | |
| 700 | 1 | |a Chow, H H |e verfasserin |4 aut | |
| 700 | 1 | |a Schneider, Claus |e verfasserin |4 aut | |
| 700 | 1 | |a Funk, Janet L |e verfasserin |4 aut | |
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