ArticlePharmaceutical biology2026
Honokiol, a structurally defined natural product, promotes SIRT3-linked bone formation in osteoporotic bone remodeling and fracture repair.
Article in Pharmaceutical biology, 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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Abstract
contextHonokiol is a structurally defined biphenolic natural product with reported mitochondrial and cytoprotective activities. Whether honokiol modifies pathological skeletal remodeling through sirtuin 3 (SIRT3)-linked mechanisms remains unclear.
objectiveThis study investigated whether honokiol regulates bone cell lineage responses and improves osteoporotic bone remodeling and fracture repair through SIRT3-associated bone formation. MATERIALS AND
methodsMouse bone marrow-derived mesenchymal stem cells and RAW264.7 cells were used to assess osteogenesis, adipogenesis, and osteoclastogenesis after recombinant SIRT3, honokiol, or SIRT3 siRNA transfection.
resultsRecombinant SIRT3 enhanced osteogenic mineralization and suppressed adipogenic differentiation and osteoclastogenesis. Honokiol increased SIRT3 expression and produced a similar lineage-shifting profile. SIRT3 knockdown markedly attenuated honokiol-induced osteogenesis, whereas its anti-adipogenic and anti-osteoclastogenic effects were only partly reduced. In ovariectomized mice, honokiol improved trabecular microarchitecture, mineral apposition, osteoblast activity, and femoral strength while reducing marrow adiposity and osteoclast burden. In fractured femora, honokiol increased mineralized callus formation, osteoblast activity, and biomechanical recovery. Local AAV-shSIRT3 intervention weakened these benefits, particularly for bone-forming and structural endpoints. DISCUSSION AND
conclusionHonokiol demonstrates a preclinical skeletal pharmacological profile characterized by predominantly SIRT3-linked bone formation. Its broader effects on adipogenic and osteoclast-associated responses appear only partly SIRT3-dependent.
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