Shao Shuai, Wei Yazi, Liu Xingtong, Zhang Tiantai
Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
Shanghai Wenyun Biotechnology Co, Ltd., Shanghai 200030, China.
Evid Based Complement Alternat Med. 2023 Feb 21;2023:1508098. doi: 10.1155/2023/1508098. eCollection 2023.
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 ( < 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 ( < 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 ( < 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% ( < 0.001) and 52% reduction ( < 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 ( < 0.001) and TNF- from 3.6 mg/ml to 1.8 ng/ml with IC value of 20.15 g/mL and 112 g/mL respectively, by activating the NF-B signaling pathway in BV-2 microglia ( < 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.
雪莲作为一种中国民族传统药物，在抗炎、免疫调节、促进血液循环等生理功能方面发挥着重要作用。它已被制成不同的中药制剂用于临床，其中雪莲口服液（XL）被广泛用于治疗类风湿性关节炎。然而，XL是否能缓解炎性疼痛及其镇痛分子机制仍不清楚。本研究探讨了XL对炎性疼痛的缓解作用及其镇痛分子机制。在完全弗氏佐剂（CFA）诱导的炎性关节疼痛中，口服XL剂量依赖性地提高了炎性疼痛的机械撤针阈值，从平均值17.8 g提高到26.6 g（P<0.05），与模型组相比，高剂量的XL显著减轻了炎症诱导的踝关节肿胀，从平均值3.1 cm降至2.3 cm（P<0.05）。此外，在角叉菜胶诱导的炎性肌肉疼痛大鼠模型中，口服XL剂量依赖性地提高了炎性疼痛的机械撤针阈值，从平均值34.3 g提高到40.8 g（P<0.05）。在CFA诱导的炎性关节疼痛中，LPS诱导的小鼠BV-2小胶质细胞和脊髓中磷酸化p65分别平均抑制了75%（P<0.001）和52%（P<0.05）。此外，结果表明，XL通过激活BV-2小胶质细胞中的NF-κB信号通路，可有效抑制IL-6的表达和分泌，从平均值2.5 ng/ml降至0.5 ng/ml（P<0.001），TNF-α从3.6 ng/ml降至1.8 ng/ml，IC50值分别为20.15 μg/mL和112 μg/mL（P<0.001）。上述结果清楚地揭示了XL中未发现的镇痛活性和作用机制。考虑到XL的显著效果，它可被评估为一种用于炎性疼痛的新型候选药物，这为扩大XL在临床治疗中的适应症建立了新的实验基础，并为开发天然镇痛药提出了可行的策略。
