Effect of Yang He Decoction on Treatment of Bone Tuberculosis via Phosphoinositide 3-Kinases/Protein Kinase B and Mitogen-Activated Protein Kinase Signaling Pathways

Abstract

Yang He Decoction (YHD), a classical Chinese medicine prescription, is used to treat bone and joint diseases. However, there are few mechanism studies for YHD on the use of YHD to treat bone tuberculosis (BT) and the corresponding mechanism of action of YHD. In the present study, the chemical ingredients of YHD and targets of the ingredients were revealed by a network pharmacology method, and an ingredient–target–disease network was visualized and analyzed. Then, gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were carried out. In addition, molecular docking was performed to clarify the binding of the key active ingredients of YHD to the key targets. Further, an in vitro model of Mycobacterium tuberculosis-induced BT was established, and a mechanism for the inhibitory effect of YHD on the differentiation of RAW 264.7 cells into osteoclasts was investigated. A total of 138 active ingredients in YHD and 50 targets between YHD ingredients and BT were identified. The phosphatidylinositol 3-kinase–protein kinase B (PI3K–Akt) and mitogen-activated protein kinase (MAPK) signaling pathways were the key pathways involved in the anti-BT effect of YHD. Moreover, the in vitro results showed that YHD inhibited the differentiation of RAW 264.7 cells into osteoclasts. YHD decreased the levels of tumor necrosis factor-α and interleukin-1β, increased the levels of superoxide dismutase and glutathione peroxide, and decreased the level of malondialdehyde. Further, YHD inhibited the protein and messenger RNA expression of PI3K/Akt, p38 MAPK, and c-Jun N-terminal kinase. These findings show that YHD is a promising anti-BT agent that suppresses the PI3K/Akt and MAPK signaling pathways to inhibit the differentiation of RAW 264.7 cells into osteoclasts and ameliorate inflammation and oxidative stress.