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

Guihong Liang; Jinlong Zhao; Di Zhao; Yaoxing Dou; Hetao Huang; Weiyi Yang; Guanghui Zhou; Zhuoxu Gu; Jianke Pan; Jun Liu

doi:10.3389/fmed.2023.1256238

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

Front Med (Lausanne). 2023 Oct 17:10:1256238. doi: 10.3389/fmed.2023.1256238. eCollection 2023.

Authors

Guihong Liang^{1

2

3}, Jinlong Zhao^{1

2

3}, Di Zhao¹, Yaoxing Dou^{1

2

3}, Hetao Huang², Weiyi Yang², Guanghui Zhou¹, Zhuoxu Gu¹, Jianke Pan^{1

2

3}, Jun Liu^{3

4

5}

Affiliations

¹ The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China.
² Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China.
³ The Research Team on Bone and Joint Degeneration and Injury of Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China.
⁴ The Fifth Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China.
⁵ Guangdong Second Chinese Medicine Hospital (Guangdong Province Enginering Technology Research Institute of Traditional Chinese Medicine), Guangzhou, China.

Abstract

Background and objective: With 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.

Methods: We 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.

Results: The 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.

Conclusion: LBJN 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.

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

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Natural Science Foundation of China (Nos. 82305263, 82004386, 81873314, and 81974574), the National Key Research and Development Program (No. 2021YFC1712804), Guangdong Basic and Applied Basic Research Foundation (Nos. 2022A1515010385, 2022A1515011700, 2022A1515220131, and 2023A1515012626), the Project of Administration of Traditional Chinese Medicine of Guangdong Province (Nos. 20241125 and 20225016), the Science and Technology Program of Guangzhou (No. 2023A03J0238), the Research Fund for Bajian Talents of Guangdong Provincial Hospital of Chinese Medicine (No. BJ2022KY01), and the Science and Technology Research Project of Guangdong Provincial Hospital of Chinese Medicine (Nos. YN2019ML08 and YN2020MS16).