Exploring the Mechanisms of Modified Bu-Shen-Yi-Qi Decoction for COPD-Related Osteoporosis Therapy via Transcriptomics and Network Pharmacology Approach

Yuanyuan Zhong,1,2 Bin Wang,1,2 Wenjing Chen,1,2 Hongying Zhang,1,2 Jing Sun,1,2 Jingcheng Dong1,2 1Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Institute of Integrated Traditional Chinese and Western Medicine, Huashan Hospital, Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Jingcheng Dong; Jing Sun, Email jcdong2004@126.com; sjing0610@163.comPurpose: To investigate the effectiveness of modified Bu-Shen-Yi-Qi decoction (MBSYQ) in the treatment of osteoporosis associated with chronic obstructive pulmonary disease (COPD) and its underlying mechanisms of action.Methods: Disease targets, active ingredients and targets were predicted by TTD, CTD, DisGeNET, HERB (BenCaoZuJian as its Chinese name), and multiple-TCM databases; In addition, the screened targets were performed via the online platforms DAVID 6.8 and Metascape for GO and KEGG pathway enrichment analysis; The relationship between the MBSYQ and core targets were verified by molecular docking technique. Then we established a COPD-associated osteoporosis rat model by passive 24-week cigarette exposure. We assessed the efficacy of MBSYQ by lung histopathology assessment and distal femur/the first lumbar vertebra (L1) microstructural assay. In addition, we performed tibial RNA sequencing, which was validated by RT-PCR and Western blot.Results: Screening revealed that the 350 active compounds of MBSYQ anchored 228 therapeutic targets for COPD-related osteoporosis; KEGG pathway enrichment analysis showed that the key targets mainly regulated MAPK and PI3K/AKT signaling pathways. In vivo studies showed that MBSYQ treatment alleviated pathological alterations in lung tissue, and reversed the bone loss and microstructure damage in the femur/L1 of model rats. The RNA seq indicated that MBSYQ could upregulate genes associated with anti-oxidative stress and aerobic respiration. The GSEA analysis displayed that MAPK and PI3K/AKT pathways were inhibited by CS exposure and activated by MBSYQ.Conclusion: MBSYQ is effective in the prevention and treatment of COPD-related osteoporosis, partially achieved by improving oxygen metabolism and activating MAPK and PI3K/AKT pathways.Keywords: COPD, osteoporosis, modified Bu-Shen-Yi-Qi formulae, network pharmacology, transcriptomics