Longbie capsules reduce bone loss in the subchondral bone of rats with comorbid osteoporosis and osteoarthritis by regulating metabolite alterations

Frontiers in Medicine

Medicine

Hetao Huang¹  Weiyi Yang¹  Jun Liu²  Di Zhao³  Zhuoxu Gu³  Guanghui Zhou³  Jianke Pan⁴  Jinlong Zhao⁴  Yaoxing Dou⁴  Guihong Liang⁴ 

[1] Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China;The Research Team on Bone and Joint Degeneration and Injury of Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China;The Fifth Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China;Guangdong Second Chinese Medicine Hospital (Guangdong Province Enginering Technology Research Institute of Traditional Chinese Medicine), Guangzhou, China;The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China;The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China;Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China;The Research Team on Bone and Joint Degeneration and Injury of Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China;

关键词: geriatric medicine;    bone aging;    osteoarthritis;    osteoporosis;    Longbie capsule;    plant-based natural products;    metabonomics;    bone metabolism;   

DOI  :  10.3389/fmed.2023.1256238

 received in 2023-07-10, accepted in 2023-09-25,  发布年份 2023

来源: Frontiers

【 摘 要 】

Background and objectiveWith the development of global population aging, comorbidity (≥2 diseases) is a common health problem among elderly people. Osteoarthritis (OA) and osteoporosis (OP) are common in elderly individuals. There is a lack of drug therapy for OA and OP comorbidities. The purpose of this study was to explore the efficacy and mechanism of Longbie capsule (LBJN), which contains various plant herbs, in treating OA and OP comorbidities (OA + OP) in rats using metabolomics techniques.MethodsWe created an OA + OP rat model through bilateral oophorectomy combined with meniscus instability surgery. Thirty SD rats were randomly divided into five groups (six in each group), namely, the sham group, OA group, OA + OP group, LBJN low-dose group (0.625 g/kg, OA + OP+LB-L group) and LBJN high-dose group (1.25 g/kg, OA + OP+LB-H group). After 8 weeks of intervention, we used micro-CT to detect bone microstructure status, ELISA to measure bone metabolism indicators, and UPLC–MS technology for metabolomics analysis. Finally, the screened differentially expressed metabolites were subjected to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and functional enrichment analysis.ResultsThe micro-CT results showed that LBJN significantly improved the bone mineral density (BMD) and bone quality of subchondral bone in OA + OP rats, and LBJN regulated the expression of bone alkaline phosphatase (BALP), osteoprotegerin (OPG), and tartrate-resistant acid phosphatase (TRACP) in serum to maintain bone metabolism balance. Metabolomics analysis showed that the metabolic trajectory of OA + OP rats after intervention in the OA + OP+LB-H group showed significant changes, and 107 potential biomarkers could be identified. Among them, 50 metabolites were upregulated (such as zeranol) and 57 were downregulated (such as vanillactic acid). The KEGG functional enrichment results indicated that the differentially expressed metabolites are mainly involved in amino acid metabolism, lipid metabolism, and carbohydrate metabolism. The KEGG pathway enrichment results indicated that LBJN may exert therapeutic effects on OA + OP rats by regulating the cAMP signaling pathway, and the FoxO signaling pathway.ConclusionLBJN can maintain bone metabolism balance by regulating serum lipid metabolism, amino acid metabolism, carbohydrate metabolism, and estrogen, thereby reducing bone loss in subchondral bone, which may be a potential mechanism through which LBJN treats OA + OP.

【 授权许可】

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Copyright © 2023 Liang, Zhao, Zhao, Dou, Huang, Yang, Zhou, Gu, Pan and Liu.