Multitech-Based Study on Medicinal Material Basis and Action Mechanism of Herbal Formula Xian-Ling-Gu-Bao Capsule in Treatment of Osteoarthritis

Currently, osteoarthritis (OA) is thought to be the most prevalent chronic joint disease worldwide. The epidemiology of this disorder is complex, and the treatment is challenging. Xian-Ling-Gu-Bao (XLGB) capsule, a herbal compound preparation, is widely used for the treatment of bone disorders, including OA. Although its efficacy and safety have been demonstrated in clinical trials and practice, the underlying medicinal constituents and mechanism have not been clearly elucidated. Therefore, this study aimed to explore the medicinal constituents and mechanism of XLGB for OA treatment. The phytochemical constituents in XLGB capsule were detected by liquid chromatography-mass spectrometry (LC-MS), the medicinal constituents and therapeutic mechanism for OA treatment were deduced by network analysis, and the deduced mechanism was validated by in vitro experiment. As a result, a total of 55 constituents were detected in XLGB extract, in which 16 constituents were screened out for target collection. Based on the analysis of target profile, XLGB targets showed a high degree of similarity with OA targets. Network analysis revealed that XLGB had a holistic effect of multiple active constituents on multiple targets and pathways. The core targets of XLGB were presumed to be MAPKs, PI3K, AKT, BCL2, RELA, TNF, NOS2, and so on, and the mechanism was speculated to mainly inhibit chondrocyte apoptosis and inflammatory response through JNK and PI3K/AKT/NF-κB signaling cascades. Finally, in vitro study confirmed that XLGB extract protected ATDC5 cells against lipopolysaccharide- (LPS-) induced apoptosis and inflammatory response, and these effects were supposed to be involved in the inhibition of JNK and PI3K/AKT/NF-κB pathways. Our study could provide a scientific basis for further research and clinical use of XLGB capsule.