Investigation of Anti-osteoporosis Mechanisms of Rehmanniae Radix Preparata Based on Network Pharmacology and Experimental Verification

Abstract

\n Background: Rehmanniae Radix Preparata (RRP) can effectively improve the symptoms of osteoporosis, but its molecular mechanism for treating osteoporosis is still unclear. The objective of this study is to investigate anti-osteoporosis mechanisms of RRP through network pharmacology.Methods: The overlapping targets of RRP and osteoporosis were screened out using online platforms. A visual network diagram of PPI was constructed and analyzed by Cytoscape 3.7.2 software. Molecular docking was used to evaluate the binding activity of ligands and receptors, and some key genes were randomly verified through pharmacological experiments. Results: According to topological analysis results, AKT1, MAPK1, ESR1, SRC, and MMP9 are key genes for RRP to treat osteoporosis, and they have high binding activity with stigmasterol and sitosterol. The main signal pathways of RRP in the treatment of osteoporosis, including Estrogen signaling pathway, HIF-1 signal pathway, MAPK signal pathway, PI3K-Akt signal pathway, etc. Results of animal experiments showed that RRP could significantly increase the expression levels of Akt1, ESR1 and SRC-1 mRNA in bone tissue to promote bone formation. Conclusion: This study explained the coordination between multiple components and multiple targets of RRP in the treatment of osteoporosis, and provided new ideas and basis for its clinical application and experimental research.