2. Academic Validation
  3. Functional calibration of PPARγ by baicalein reverses bone-lipid imbalance in type 2 diabetic osteoporosis

Functional calibration of PPARγ by baicalein reverses bone-lipid imbalance in type 2 diabetic osteoporosis

  • Phytomedicine. 2026 Mar:152:157850. doi: 10.1016/j.phymed.2026.157850.
Hua Zhang 1,  Bai Hao Chen 2,  Jianan Huang 1,  Junzheng Yang 2,  Jiacong Xiao 1,  Peng Chen 3
Affiliations

Affiliations

  • 1 State Key Laboratory of Traditional Chinese Medicine Syndromes, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510405, PR China; The Laboratory of Orthopaedics and Traumatology of Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, PR China.
  • 2 State Key Laboratory of Traditional Chinese Medicine Syndromes, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510405, PR China; Guangdong Second Traditional Chinese Medicine Hospital (Guangdong Province Engineering Technology Research Institute of Traditional Chinese Medicine), Guangzhou, 510095, PR China; The Laboratory of Orthopaedics and Traumatology of Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, PR China.
  • 3 State Key Laboratory of Traditional Chinese Medicine Syndromes, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510405, PR China; The Laboratory of Orthopaedics and Traumatology of Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, PR China; Hongxing Hospital of the 13th Division of Xinjiang Production and Construction Corps, Xinjiang Uygur Autonomous Region, 839000, PR China. Electronic address: [email protected].
PMID: 41581447 DOI: 10.1016/j.phymed.2026.157850
Abstract

Background: Type 2 diabetic osteoporosis (T2DOP) is characterized by excessive bone marrow adiposity and impaired osteogenesis, a pathology driven primarily by PPARγ-mediated dysregulation of the osteogenic-adipogenic differentiation balance in BMSCs under hyperglycemic conditions. Baicalein (BCL) is a natural flavonoid and a key active constituent of Gegen Qinlian Decoction (GQD), has shown regulatory potential in various metabolic disorders. However, its specific role and underlying mechanisms in T2DOP remain to be fully elucidated.

Methods: We treated db/db mice with BCL for 8 weeks. Micro-CT and histomorphometric analyses evaluated bone microarchitecture, while histochemical staining assessed marrow adiposity. Immunohistochemistry and Western blot analysis examined the expression of osteogenic and adipogenic markers. In vitro, we subjected high glucose-treated BMSCs to osteogenic/adipogenic induction in the presence of BCL. Differentiation was evaluated by ARS and Oil Red O staining. Furthermore, we employed molecular docking, CETSA, and molecular dynamics simulations to confirm direct binding between BCL and PPARγ.

Results: BCL significantly increased bone mineral density and trabecular number in db/db mice, while reducing marrow fat accumulation. In vitro, it promoted mineralization and suppressed lipid droplet formation. BCL downregulated PPARγ and adipogenic genes and enhanced osteogenic markers (RUNX2, COL1A, OCN). Mechanistically, it bound strongly to the PPARγ ligand-binding domain, acting as a microenvironment-dependent modulator that recalibrates its transcriptional activity toward osteogenesis.

Conclusion: BCL attenuates T2DOP by directly targeting PPARγ and restoring its bone-lipid balance.

Keywords

BCL; BMSCs differentiation; Bone- lipid balance; PPARγ signaling; Type 2 diabetic osteoporosis.

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