Muzhe Li , Yuanyuan Niu , Tianchi Zhang , Haomiao Yang , Linkun Tian , Shijie Zhou , Taxi Wumiti , Jie Sun , Qinfeng Zhou , Xinchen Zuo , Tianle Gao , Jiale Li , Yong Ma , Yang Guo , Lining Wang
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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<sup>+</sup>/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<sup>+</sup>/NADH, and WB.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusions</h3><div>By increasing testosterone production, WSTLZTD may promote mitochondrial energy metabolism and osteogenic differentiation of senescent BMSCs, thereby exerting its anti-SOP effect.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"338 ","pages":"Article 119033"},"PeriodicalIF":4.8000,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Wen-Shen-Tong-Luo-Zhi-Tong-Decoction inhibits bone loss in senile osteoporosis model mice by promoting testosterone production\",\"authors\":\"Muzhe Li , Yuanyuan Niu , Tianchi Zhang , Haomiao Yang , Linkun Tian , Shijie Zhou , Taxi Wumiti , Jie Sun , Qinfeng Zhou , Xinchen Zuo , Tianle Gao , Jiale Li , Yong Ma , Yang Guo , Lining Wang\",\"doi\":\"10.1016/j.jep.2024.119033\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Ethnopharmacological relevance</h3><div>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.</div></div><div><h3>Aim of the study</h3><div>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.</div></div><div><h3>Materials and methods</h3><div>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<sup>+</sup>/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<sup>+</sup>/NADH, and WB.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusions</h3><div>By increasing testosterone production, WSTLZTD may promote mitochondrial energy metabolism and osteogenic differentiation of senescent BMSCs, thereby exerting its anti-SOP effect.</div></div>\",\"PeriodicalId\":15761,\"journal\":{\"name\":\"Journal of ethnopharmacology\",\"volume\":\"338 \",\"pages\":\"Article 119033\"},\"PeriodicalIF\":4.8000,\"publicationDate\":\"2024-11-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of ethnopharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0378874124013321\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of ethnopharmacology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0378874124013321","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Wen-Shen-Tong-Luo-Zhi-Tong-Decoction inhibits bone loss in senile osteoporosis model mice by promoting testosterone production
Ethnopharmacological relevance
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.
Aim of the study
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.
Materials and methods
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.
Results
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.
Conclusions
By increasing testosterone production, WSTLZTD may promote mitochondrial energy metabolism and osteogenic differentiation of senescent BMSCs, thereby exerting its anti-SOP effect.
期刊介绍：
The Journal of Ethnopharmacology is dedicated to the exchange of information and understandings about people''s use of plants, fungi, animals, microorganisms and minerals and their biological and pharmacological effects based on the principles established through international conventions. Early people confronted with illness and disease, discovered a wealth of useful therapeutic agents in the plant and animal kingdoms. The empirical knowledge of these medicinal substances and their toxic potential was passed on by oral tradition and sometimes recorded in herbals and other texts on materia medica. Many valuable drugs of today (e.g., atropine, ephedrine, tubocurarine, digoxin, reserpine) came into use through the study of indigenous remedies. Chemists continue to use plant-derived drugs (e.g., morphine, taxol, physostigmine, quinidine, emetine) as prototypes in their attempts to develop more effective and less toxic medicinals.
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