Abstract
This study aimed to identify whether the NF-κB signaling pathway plays a key role in the treatment of osteoarthritis (OA) with Bushen Zhuangjin Decoction (BZD) based on a typical network pharmacology approach (NPA). Four sequential experiments were performed: 1) conventional high-performance liquid chromatography (HPLC), 2) preliminary observation of the therapeutic effects of BZD, 3) NPA using three OA-related gene expression profiles, and 4) verification of the key pathway identified by NPA. Only one HPLC-verified compound (paeoniflorin) was identified from the candidate compounds discovered by NPA. The genes verified in the preliminary observation were also identified by NPA. NPA identified a key role for the NF-κB signaling pathway in the treatment of OA with BZD, which was confirmed by conventional western blot analysis. This study identified and verified NF-κB signaling pathway as the most important inflammatory signaling pathway involved in the mechanisms of BZD for treating OA by comparing the NPA results with conventional methods. Our findings also indicate that NPA is a powerful tool for exploring the molecular targets of complex herbal formulations, such as BZD.
Highlights
Osteoarthritis (OA) is common in the aging population
Changes of Matrix Metallopeptidase (MMP)-9, IL-6 and NF-κB p65 levels were used as preliminary indicators of the activation of the NF-κB signaling pathway
Our results indicate that network pharmacology approach (NPA) is a powerful tool to identify molecular targets incomplex herbal formulation commonly used in traditional Chinese medicine (TCM)
Summary
Osteoarthritis (OA) is common in the aging population. It has been regarded as a severe public health concern since it remarkably reduces quality of life (Ashraf et al, 2018; Kwon et al, 2018). Many previous studies have documented the involvement of molecules and inflammatory signaling pathways in the development and progression of OA by regulation of the oxidative stress, cellular apoptosis, inflammatory response and microRNAs (Miyaki and Asahara, 2012; Mobasheri et al, 2015; Bouderlique et al, 2016; Saito and Tanaka, 2017). Jimi et al documented that NF-κB signaling pathway plays a key role in the regulation of the normal development and pathological destruction of cartilage (Jimi et al, 2019). Choi et al summarized that a comprehensive understanding of the roles of NF-κB signaling pathway is useful in the development of novel therapies against OA (Choi et al, 2019)
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