School of Life Science and Technology, Shandong Second Medical University, Weifang 261053, Shandong Province, PR China.
Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, PR China.
Int Immunopharmacol. 2024 Nov 15;141:112918. doi: 10.1016/j.intimp.2024.112918. Epub 2024 Aug 18.
Inflammatory pain is a chronic pain caused by peripheral tissue inflammation, seriously impacting the patient's life quality. Cinobufacini injection, as a traditional Chinese medicine injection preparation, shows excellent efficacy in anti-inflammatory and analgesic treatment in patients with advanced tumors. In this study, a novel analgesic peptide CI5 with anti-inflammatory and analgesic bio-functions that naturally presents in Cinobufacini injection and its regulatory mechanism are reported. Our results showed that the administration of CI5 significantly relieved the pain of mice in the acetic acid twisting analgesic model and formalin inflammatory pain model. Furthermore, CI5 effectively reduced the inflammatory cytokines (IL-6, TNF-α and IL-1β) and inflammatory mediator (PGE2) expressions, and prevented the carrageenan-induced paw edema in mice. Further LC-MS/MS results showed the anti-inflammatory and analgesic bio-functions of CI5 depended on its interaction with the Rac-2 protein upstream of ERK1/2 and the inflammatory signaling pathway (ERK1/2/COX-2 axis). In summary, CI5, as a novel natural candidate identified from Cinobufacini injection, showed substantial clinical promise for inflammatory pain treatments.
炎性疼痛是由外周组织炎症引起的慢性疼痛，严重影响患者的生活质量。华蟾素注射液作为一种中药注射制剂，在晚期肿瘤患者的抗炎和镇痛治疗中显示出优异的疗效。本研究报道了一种天然存在于华蟾素注射液中的新型抗炎镇痛生物活性肽 CI5 及其调控机制。研究结果表明，CI5 给药可显著缓解醋酸扭体镇痛模型和福尔马林炎症性疼痛模型中小鼠的疼痛。此外，CI5 可有效降低炎性细胞因子（IL-6、TNF-α 和 IL-1β）和炎性介质（PGE2）的表达，并预防角叉菜胶诱导的小鼠足肿胀。进一步的 LC-MS/MS 结果表明，CI5 的抗炎和镇痛生物活性取决于其与 Rac-2 蛋白上游 ERK1/2 和炎症信号通路（ERK1/2/COX-2 轴）的相互作用。总之，CI5 作为从华蟾素注射液中鉴定的一种新型天然候选药物，为炎性疼痛治疗提供了有前景的临床应用。
