Institute of Pharmacology, School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, No. 548 Binwen Road, Binjiang District, Hangzhou, 310053, China.
Department of Pharmacy, The Affiliated Hospital of Medical School of Ningbo University, Ningbo, 315020, China.
Neurotox Res. 2022 Aug;40(4):1057-1069. doi: 10.1007/s12640-022-00531-5. Epub 2022 Jun 14.
Neuropathic pain (NP) is a common disorder among individuals worldwide, but there is still no effective treatment for NP. The EGFR pathway promotes NP nociceptive sensitization and represents a potential therapeutic target. Geniposide is abundant in natural plants and has various pharmacological activities, such as analgesia and anti-inflammation properties, which can improve NP, but the specific mechanisms have not been elucidated. The present study first predicted and molecularly docked geniposide targets, suggesting that geniposide may play a role in improving NP by targeting EGFR. This study further clarified that geniposide alleviates NP and improves the inflammatory response using a chronic constriction injury (CCI) model, whereas the administration of an EGFR agonist weakens the above effects of geniposide. Analysis of transcriptome data further suggests that geniposide not only improves CCI symptoms by reducing EGFR/PI3K/AKT pathway activity but also may exert anti-inflammatory effects by inhibiting the Ca signaling pathway. The above results affirm the potential value of geniposide in the treatment of NP and lay the foundation for further clinical application.
神经病理性疼痛（NP）是一种常见的疾病，在全球范围内影响着许多人，但目前仍没有有效的治疗方法。EGFR 通路促进 NP 伤害性敏化，代表了一个潜在的治疗靶点。京尼平苷广泛存在于天然植物中，具有多种药理活性，如镇痛和抗炎作用，可以改善 NP，但具体机制尚未阐明。本研究首先预测并分子对接了京尼平苷的靶点，提示京尼平苷可能通过靶向 EGFR 发挥改善 NP 的作用。本研究进一步通过慢性缩窄性损伤（CCI）模型阐明了京尼平苷缓解 NP 和改善炎症反应的作用，而 EGFR 激动剂的给药则削弱了京尼平苷的上述作用。转录组数据分析进一步表明，京尼平苷不仅通过降低 EGFR/PI3K/AKT 通路活性来改善 CCI 症状，而且还可能通过抑制 Ca 信号通路发挥抗炎作用。上述结果肯定了京尼平苷在治疗 NP 中的潜在价值，并为进一步的临床应用奠定了基础。
