Xueliankoufuye Suppresses Microglial Activation with Inflammatory Pain by Blocking NF-κB Signaling Pathway

Xuelian, as a traditional Chinese ethnodrug, plays an important role in anti-inflammation, immunoregulation, promoting blood circulation, and other physiological functions. It has been prepared into different traditional Chinese medicine preparations for clinical use, with xuelian koufuye (XL) being widely used to treat rheumatoid arthritis. However, whether XL can relieve inflammatory pain and its analgesic molecular mechanism are still unknown. The present study explored the palliative effect of XL on inflammatory pain and its analgesic molecular mechanism. In complete Freund's adjuvant (CFA)-induced inflammatory joint pain, oral XL dose-dependently improved the mechanical withdrawal threshold of inflammatory pain from an average value of 17.8 g to 26.6 g (P < 0.05) and high doses of XL significantly reduced inflammation-induced ankle swelling from an average value of 3.1 cm to 2.3 cm compared to the model group (P < 0.05). In addition, in carrageenan-induced inflammatory muscle pain rat models, oral XL dose-dependently improved the mechanical withdrawal threshold of inflammatory pain from an average value of 34.3 g to 40.8 g (P < 0.05). The phosphorylated p65 was inhibited in LPS-induced BV-2 microglia and spinal cord of mice in CFA-induced inflammatory joint pain within a value of 75% (P < 0.001) and 52% reduction (P < 0.05) on average, respectively. In addition, the results showed that XL could effectively inhibit the expression and secretion of IL-6 from an average value of 2.5 ng/ml to 0.5 ng/ml (P < 0.001) and TNF-α from 3.6 mg/ml to 1.8 ng/ml with IC₅₀ value of 20.15 μg/mL and 112 μg/mL respectively, by activating the NF-κB signaling pathway in BV-2 microglia (P < 0.001). The above-given results provide a clear understanding of the analgesic activity and mechanism of action not found in XL. Considering the significant effects of XL, it can be evaluated as a novel drug candidate for inflammatory pain, which establishes a new experimental basis for expanding the indications of XL in clinical treatment and suggests a feasible strategy to develop natural analgesic drugs.