Evidence map›Paper›PMID 42581191›Full record

ArticleBiogerontology2026

Isoorientin attenuates aging-induced bone deterioration by suppressing M1-mediated TLR4-MAPK-NF-κB inflammatory signaling.

Jinku Guo, Jun Xie, Ankai Xu, Wei Wang, Zhiqiang Fu, Kening Zhou, Shengkun Hong

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Article in Biogerontology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

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7 authors.

Jinku GuoDepartment of Orthopedics, The Quzhou Affiliated Hospital, Wenzhou Medical University, No.100, Minjiang Avenue, Quzhou, 324000, Zhejiang Province, China.
Jun XieDepartment of Orthopedics, The Quzhou Affiliated Hospital, Wenzhou Medical University, No.100, Minjiang Avenue, Quzhou, 324000, Zhejiang Province, China.
Ankai XuDepartment of Orthopedics, The Quzhou Affiliated Hospital, Wenzhou Medical University, No.100, Minjiang Avenue, Quzhou, 324000, Zhejiang Province, China.
Wei WangDepartment of Orthopedics, The Quzhou Affiliated Hospital, Wenzhou Medical University, No.100, Minjiang Avenue, Quzhou, 324000, Zhejiang Province, China.
Zhiqiang FuDepartment of Orthopedics, The Quzhou Affiliated Hospital, Wenzhou Medical University, No.100, Minjiang Avenue, Quzhou, 324000, Zhejiang Province, China.
Kening ZhouDepartment of Gynecology, The Quzhou Affiliated Hospital, Wenzhou Medical University, Quzhou, 324000, Zhejiang Province, China.
Shengkun HongDepartment of Orthopedics, The Quzhou Affiliated Hospital, Wenzhou Medical University, No.100, Minjiang Avenue, Quzhou, 324000, Zhejiang Province, China. hongshengkun@163.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAging disrupts bone remodeling by increasing osteoclast activity, reducing osteogenic capacity, and elevating inflammation. Toll-like receptor 4 (TLR4)-mediated inflammatory signaling has been implicated in bone degeneration, yet its role in age-related skeletal decline remains incompletely understood. Isoorientin, a plant-derived flavonoid with reported anti-inflammatory properties, has not been evaluated in the context of skeletal aging.

methodsBone aging was first assessed in C57BL/6 J mice using micro-computed tomography (μCT), histology, TRAP staining, and immunofluorescence. The effects of isoorientin on osteogenesis were examined in senescent hBMSCs by alkaline phosphatase (ALP) activity, mineralization assays, and expression of osteogenesis-related genes. LPS-stimulated RAW264.7 cells were used to evaluate inflammatory responses and M1/M2 polarization. To assess TLR4/ mitogen-activated protein kinase (MAPK)/ nuclear factor-κB (NF-κB) regulation, RAW264.7 cells were treated with TAK-242 or TAK-242 plus isoorientin. Finally, aged mice were treated with isoorientin, TAK-242, or both to evaluate in vivo pathway modulation and bone protection.

resultsAged mice exhibited reduced trabecular mass, elevated osteoclast activity, and increased osteoclast-associated markers. Isoorientin treatment improved trabecular structure, decreased osteoclast numbers, and lowered osteoclast-associated proteins. In senescent hBMSCs, isoorientin restored ALP activity, enhanced mineral deposition, and increased osteogenic marker expression. Isoorientin also reduced pro-inflammatory cytokines, suppressed M1 polarization, and inhibited TLR4/MAPK/NF-κB activation. The combination of isoorientin and TAK-242 exhibited the most potent suppression of inflammatory signaling and the most significant enhancement in bone microarchitecture.

conclusionIsoorientin alleviates age-related bone loss by suppressing TLR4-mediated inflammation, reducing osteoclast activation, and restoring impaired osteogenesis. These findings identify isoorientin as a promising therapeutic candidate for age-associated osteoporosis.

Indexed as

AgingLuteolinNF-kappa BToll-Like Receptor 4AnimalsBone RemodelingInflammationMaleMiceMice, Inbred C57BLMitogen-Activated Protein KinasesOsteogenesisRAW 264.7 CellsSignal TransductionhomoorientinLuteolinMitogen-Activated Protein KinasesNF-kappa BTlr4 protein, mouseToll-Like Receptor 4IsoorientinMAPKNF-κB pathwaySkeletal agingTLR4 signaling

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.