Predication of the underlying mechanism of Bushenhuoxue formula acting on knee osteoarthritis via network pharmacology-based analyses combined with experimental validation. (5th December 2020)

• Record Type: Journal Article
• Authors: Xu, Hui-Hui; Li, Suo-Mi; Xu, Rui; Fang, Liang; Xu, Hui; Tong, Pei-Jian
• Is Part Of: Journal of ethnopharmacology. Volume 263(2020)
• Publication Date: 2020-12-05
• Subjects: Bushenhuoxue formula -- Network pharmacology -- Knee osteoarthritis -- Apoptosis; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2020.113217
• Languages: English
• ISSNs: 0378-8741

Abstract

Abstract: Ethnopharmacological relevance: Knee osteoarthritis (KOA) is the most common chronic joint disorder worldwide, which is also a principle consideration for disability. The Bushenhuoxue formula (BSHXF) is a traditional herbal formula which widely applied to the treatment of KOA. However, its pharmacological mechanisms of action have not been clarified. Aims of the study: The study aimed to identify the potential targets and mechanisms of BSHXF in the treatment of KOA through pharmacology-based analyses and experimental validation. Materials and methods: The TCMSP database was applied to obtain the chemical compounds and targets of BSHXF, while the protein targets in KOA were determined through GeneCards and OMIM databases. The herb-compound-target and protein-protein interaction (PPI) networks were constructed for topological analyses and hub-targets screening. GO and KEGG enrichment analyses were performed on these core nodes to identify the critical biological processes and signaling pathways. Then destabilization of medial meniscus (DMM)-induced C57BL/6J mice model was established to detect the level of apoptosis via TUNEL assessment, while the expressions of CASP3, CASP8 and CASP9 were determined by immunohistochemistry. Results: A total of 154 active compounds and 58 targets were predicted. DAVID, ClueGO and Metascape enrichment analyses all proved that BSHXF plays an essential role in regulating apoptosis. Moreover, 3 central nodes of BSHXF are recognized as the active factors involved in the main biological functions, suggesting a potential mechanism of BSHXF for KOA treatment. In vivo experiment revealed that BSHXF significantly inhibited apoptosis and down-regulated the expressions of CASP3, CASP8 and CASP9. Conclusion: Based on network pharmacology and experimental validation, our study indicated that BSHXF exerted anti-apoptosis effect through inhibiting the expressions of CASP3, CASP8 and CASP9, which could be considered as an effective method for KOA treatment. Graphical abstract: Image 1 Highlights: Exploring the exact mechanism of BSHXF in the treatment of KOA. Comprehensive verification of network pharmacology combined with experiment. The first study showing BSHXF treat KOA by inhibiting apoptosis.