| Objective To investigate the therapeutic effect and mechanism of the Mongolian drug Tonglaga-5 (TLG-5) on the retinoic acid-induced osteoporosis (OP) in rats. Methods Thirty SD female rats were randomly divided into blank group, model group, positive drug group (alendronate tablet group), TLG-5 low dose group, and TLG-5 high dose group, with six rats in each group. The OP rat model was induced by retinoic acid. The serum levels of ALP, β-ALP, CTX-1, PINP, OST, and ACP-5 were detected with ELISA. The levels of BMD, BV/TV, Tb.N, Tb.Th, and Tb.Sp in the tibia were analyzed with micro-CT. The maximal loading capacity of the tibia was tested. The expression level of TRAP in the radius was observed and analyzed with TRAP staining in each group. HPLC-Q-Exactive-MS/MS was used to analyze the serum endogenous metabolites in each group of rats to identify the biomarkers and metabolic pathways in TLG-5-treated OP rats. Results TLG-5 significantly regulated serum ALP, β-ALP, CTX-1, OST, PINP, and ACP-5 levels in OP rats, increased BMD, BV/TV, Tb.N, Tb.Th levels, and decreased Tb.Sp levels in the tibia; enhanced tibia maximal loading capacity; and decreased TRAP expression levels in the radius. Twenty-two biomarkers in TLG-5-regulated osteoporosis were screened using metabolomics. Seven metabolic pathways were obtained with enrichment, among which pyrimidine metabolism, fatty acid biosynthesis, and bile acid biosynthesis were the main metabolic pathways regulated by TLG-5 to relieve OP in rats. Conclusion TLG-5 exerts its role in relieving OP by regulating 22 biomarkers and 7 major metabolic pathways in rats. |