Work

Kun-Ling Wan Formula Ameliorates Postmenopausal Osteoporosis and Adipose Accumulation by Suppressing mTOR Signaling in Mesenchymal Stem Cells

Year: 2026

Type: article

Abstract: Background: Postmenopausal osteoporosis is a common metabolic bone disorder characterized by decreased bone mass and microstructural deterioration, often accompanied by increased bone marrow adiposity and systemic fat accumulation. Kun-Ling Wan Formula (KLW) is a compound Chinese medicine clinically used for gynecological disorders, though its effects on postmenopausal osteoporosis and associated fat accumulation remain unclear. Distinct from previous herbal formulation studies that primarily focused on bone outcomes, our study uniquely integrates bone protection, marrow adiposity reduction, systemic metabolic improvement, and multi-omics mechanistic dissection in a high-fat diet-fed ovariectomized mouse model. Methods: KLW chemical composition was analyzed by UPLC-Q-TOF/MS. Ovariectomized (OVX) C57BL/6J mice fed high-fat or normal diet were treated with KLW at clinically equivalent or double doses, with estrogen and active compounds as controls. Bone microstructure was assessed by micro-CT, bone marrow fat by MRI-PDFF, and metabolism by OGTT, ITT, and metabolic cages. Network pharmacology, proteomics, molecular docking, and dynamics simulations identified core targets. C3H10T1/2 cells were used to assess osteogenic/adipogenic differentiation and mTOR pathway activation. Results: Twelve compounds were identified in KLW. In OVX mice, KLW significantly improved bone mineral density and trabecular microstructure, reduced adiposity and bone marrow fat, and enhanced glucose tolerance and insulin sensitivity. In vitro, KLW promoted osteogenesis and suppressed adipogenesis in C3H10T1/2 cells. Integrative analyses identified mTOR as a central target, with chrysophanol, pyrogallol, and apigenin showing high-affinity binding. KLW inhibited mTOR/S6K phosphorylation during differentiation, an effect reversible by leucine. Conclusions: KLW ameliorates osteoporosis and reduces fat accumulation in OVX mice by shifting mesenchymal stem cell differentiation toward osteogenesis via mTOR pathway modulation.

Source: Pharmaceuticals

DOI: 10.3390/ph19050719