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Isoorientin attenuates aging-induced bone deterioration by suppressing M1-mediated TLR4-MAPK-NF-κB inflammatory
Jinku Guo1, Jun Xie1, Ankai Xu1
1Department of Orthopedics, The Quzhou Affiliated Hospital, Wenzhou Medical University, No.100, Minjiang Avenue, Quzhou, 324000, Zhejiang Province, China.
Biogerontology
|August 11, 2026
Summary
Isoorientin, a natural flavonoid, combats age-related bone loss by reducing inflammation and enhancing bone formation. This study highlights its potential for treating osteoporosis.
Area of Science:
- Skeletal Biology
- Immunology
- Pharmacology
Background:
- Aging impairs bone remodeling by increasing osteoclast activity and inflammation.
- Toll-like receptor 4 (TLR4) signaling is implicated in bone degeneration.
- The effects of isoorientin on skeletal aging were previously unevaluated.
Purpose of the Study:
- To investigate the effects of isoorientin on age-related bone loss.
- To elucidate the role of TLR4 in age-related bone decline.
- To assess isoorientin's therapeutic potential for osteoporosis.
Main Methods:
- Assessed bone aging in mice using micro-CT, histology, and TRAP staining.
- Examined isoorientin's effects on osteogenesis in human bone marrow stromal cells (hBMSCs).
- Evaluated inflammatory responses and M1/M2 polarization in LPS-stimulated RAW264.7 cells.
- Investigated TLR4/MAPK/NF-κB pathway regulation.
- Assessed in vivo effects of isoorientin and TAK-242 on aged mice.
Main Results:
- Aged mice showed reduced bone mass and increased osteoclast activity.
- Isoorientin treatment improved bone structure and decreased osteoclast markers.
- Isoorientin restored osteogenic capacity in senescent hBMSCs.
- Isoorientin suppressed inflammation and TLR4/MAPK/NF-κB activation.
- Combined isoorientin and TAK-242 showed potent anti-inflammatory and bone-protective effects.
Conclusions:
- Isoorientin alleviates age-related bone loss by suppressing TLR4-mediated inflammation.
- Isoorientin reduces osteoclast activation and restores impaired osteogenesis.
- Isoorientin is a promising therapeutic candidate for age-associated osteoporosis.
