Effects of Zhengqing Fengtongning in treatment Knee osteoarthritis based on TLR4/NLRP3/Caspase-3 signalling pathway

Abstract

Abstract Introduction Knee osteoarthritis (KOA) is a degenerative joint disease that leads to joint deformity and loss of function in severe cases. Its primary symptoms include joint pain, swelling, and impaired mobility. It has been reported that more than 80% of patients with knee osteoarthritis are over 60 years old, constituting a significant proportion of hospitalizations in developed countries. This imposes a substantial burden on patients, their families, and society. Currently, the drugs of choice for KOA in clinical practice are non-steroidal anti-inflammatory drugs (NSAIDs). However, their efficacy is suboptimal as they primarily alleviate symptoms, and long-term use can lead to serious adverse reactions. The focus and hotspot of orthopedic research lie in understanding the mechanism of effectively inhibiting cartilage degeneration, protecting cartilage cells and tissues, and slowing down or even reversing the progression of KOA. Methods The composition of Zhengqingfengtongning (ZQFTN) was verified using mass spectrometry. Fifteen female Wistar rats were randomly assigned to the normal group (control), KOA model group (model), Zhengqing group (ZQFTN Sustained Release Tablets), TLR4-inhibitor group (TLR4-inhibitor), and Zhengqing + TLR4-inhibitor group (ZQFTN Sustained Release Tablets and TLR4-inhibitor), with three rats in each group. Histological staining, Western blotting, and Elisa were employed to compare histomorphology and data of IL-6, IL-1β, TNF-α, TAK1, TAB1, iKBα, IKKβ, Bax, Bcl-2, and Caspase-3 in rats from each group. Results Histological staining, Western blotting, and Elisa assay results demonstrated the effectiveness of ZQFTN in improving the condition of KOA model rats. Furthermore, the expression of IL-6, IL-1β, TNF-α, TAB1, iKBα, IKKβ, and Caspase-3 levels in chondrocytes was suppressed, while Bcl-2 levels were increased. Conclusions ZQFTN ameliorated the condition of KOA model rats, and its therapeutic mechanism may involve the regulation of inflammatory factors and cellular autophagy, along with the inhibition of the TLR4/NLRP3/Caspase-3 signaling pathway.