Abstract
Purpose: The external preparation of the Tibetan medicine formula, Baimai ointment (BMO), has great therapeutic effects on osteoarthritis (OA). However, its molecular mechanism remains almost elusive. Here, a comprehensive strategy combining network pharmacology and molecular docking with pharmacological experiments was adopted to reveal the molecular mechanism of BMO against OA. Methods: The traditional Chinese medicine for systems pharmacology (TCMSP) database and analysis platform, traditional Chinese medicine integrated database (TCMID), GeneCards database, and DisGeNET database were used to screen the active components and targets of BMO in treating OA. A component–target (C-T) network was built with the help of Cytoscape, and the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment through STRING. Autodock Tools which was used to dock the key components and key target proteins was analyzed. Animal experiments were performed to verify the key targets of BMO. Hematoxylin–eosin and toluidine blue staining were used to observe the pathology of joints. Protein expression was determined using enzyme-linked immunosorbent assay. Results: Bioactive compounds and targets of BMO and OA were screened. The network analysis revealed that 17-β-estradiol, curcumin, licochalone A, quercetin, and glycyrrhizic acid were the candidate key components, and IL6, tumor necrosis factor (TNF), MAPK1, VEGFA, CXCL8, and IL1B were the candidate key targets in treating OA. The KEGG indicated that the TNF signaling pathway, NF-κB signaling pathway, and HIF-1 signaling pathway were the potential pathways. Molecular docking implied a strong combination between key components and key targets. The pathology and animal experiments showed BMO had great effects on OA via regulating IL6, TNF, MAPK1, VEGFA, CXCL8, and IL1B targets. These findings were consistent with the results obtained from the network pharmacology approach. Conclusion: This study preliminarily illustrated the candidate key components, key targets, and potential pathways of BMO against OA. It also provided a promising method to study the Tibetan medicine formula or external preparations.
Highlights
Osteoarthritis (OA) is a common chronic disease with cartilage degradation in the clinic, characterized by arthritis, synovial inflammation, joint edge, and underlying subchondral bone lesions (Krustev et al, 2015)
A collection of 44 potential compounds were collected from TCMSP and traditional Chinese medicine integrated database (TCMID) databases according to certain criteria, including 7 in Curcumae longae Rhizoma, 8 in Zanthoxyli Pericarpium, 7 in Moschus, and 22 in Glycyrrhizae Radix et Rhizoma (Table 2)
The possible molecular mechanism of action is that the candidate key components of glycyrrhizic acid, 17-β-estradiol, curcumin, licochalcone A, and quercetin act on IL6, tumor necrosis factor (TNF), MAPK1, VEGFA, CXCL8, and IL1B and these key targets regulate the TNF signaling pathway, NF-κB signaling pathway, and HIF-1 signaling pathway, so as to play a therapeutic role (Figure 8)
Summary
Osteoarthritis (OA) is a common chronic disease with cartilage degradation in the clinic, characterized by arthritis, synovial inflammation, joint edge, and underlying subchondral bone lesions (Krustev et al, 2015). Clinical manifestations include joint pain, swelling, stiffness, and even deformity with limited movement (Nüesch et al, 2011; Centers for Disease Control and Prevention, 2020). The second largest traditional Chinese medicine system in China, has rich clinical applications in treating OA with its characteristic ingredients (Ren et al, 2018; Zhang et al, 2018; Fu et al, 2020). According to the theory of Tibetan medicine, OA belongs to Baimai disease (Ren et al, 2018), and BMO can treat OA with the effect of dispersing cold together with removing dampness, removing blood stasis, and soothing tendons by improving blood circulation (Liu et al, 2007).
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