Wen-Shen-Tong-Luo-Zhi-Tong-Decoction inhibits bone loss in senile osteoporosis model mice by promoting testosterone production
Wen-Shen-Tong-Luo-Zhi-Tong-Decoction (WSTLZTD) is a traditional Chinese medicine formula, and its effectiveness in the treatment of senile osteoporosis(SOP) has been confirmed by clinical studies. However, the underlying mechanism of WSTLZTD in SOP is unclear. This study aimed to clarify the unique...
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Veröffentlicht in: | Journal of ethnopharmacology 2025-02, Vol.338 (Pt 2), p.119033, Article 119033 |
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Zusammenfassung: | Wen-Shen-Tong-Luo-Zhi-Tong-Decoction (WSTLZTD) is a traditional Chinese medicine formula, and its effectiveness in the treatment of senile osteoporosis(SOP) has been confirmed by clinical studies. However, the underlying mechanism of WSTLZTD in SOP is unclear.
This study aimed to clarify the unique effects of Wen-Shen-Tong-Luo-Zhi-Tong-Decoction(WSTLZTD) on senile osteoporosis(SOP) and its underlying mechanisms.
SAMP6 mice were treated with varying doses of WSTLZTD as the SOP model. Bone loss was evaluated by micro-CT, HE, OCN immunohistochemistry staining, and serum Trap level. Metabolomics studies serum metabolites. ELISA, qPCR, and immunofluorescence were utilized to measure testosterone levels in mouse testis. The effect of testosterone on the mitochondrial energy metabolism of BMSCs was investigated using ROS generation, NAD+/NADH ratio, and WB. Cell senescence was examined by β-galactosidase staining and WB. The effect of TM3 cell conditioned media (CM) on mitochondrial energy metabolism and BMSCs osteogenesis were studied using ALP, ARS, ROS staining, the NAD+/NADH, and WB.
WSTLZTD effectively reversed bone loss in SOP model mice, resulting in better bone microstructure, increased BMD, BV/TV, Tb.n, Tb.Th and, and decreased Tb.Sp. WSTLZTD can increase OCN expression and decrease Trap levels. Network pharmacology data suggest that WSTLZTD regulates steroid hormone production, cellular senescence, inflammation. Metabolomic data indicate that WSTLZTD increases testosterone production or metabolism-related metabolites. WSTLZTD enhanced testosterone production and the mRNA expression of genes involved in testosterone synthesis. Testosterone inhibited the decline in osteogenic differentiation and mitochondrial energy metabolism of senescent BMSCs. The decreased testosterone production in senescent TM3 is reversed by WSTLZTD. CM derived from WSTLZTD-treated TM3 cells promoted osteogenic differentiation and mitochondrial energy metabolism of BMSCs.
By increasing testosterone production, WSTLZTD may promote mitochondrial energy metabolism and osteogenic differentiation of senescent BMSCs, thereby exerting its anti-SOP effect.
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•WSTLZTD inhibited bone loss in SOP model mice.•WSTLZTD has the ability to enhance the synthesis and production of testosterone.•Testosterone inhibited the decline in mitochondrial energy metabolism of senescent BMSCs.•WSTLZTD promoted mitochondrial energy metabolism of BMSCs by increasing testosterone production. |
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ISSN: | 0378-8741 1872-7573 1872-7573 |
DOI: | 10.1016/j.jep.2024.119033 |