Hai Qingshan, Wang Yuming, Li Hanzhou, Pei Huan, Wang Ning, Zhang Xiaoxia, Fan Mingyao, Liao Jiabao, Wen Weibo, Zhao Jie, Yang Ling, Cui Huantian
Nanjing University of Chinese Medicine, Nanjin, China.
Basic Medical School, Yunnan University of Chinese Medicine, Kunming, China.
J Cell Mol Med. 2025 Apr;29(8):e70571. doi: 10.1111/jcmm.70571.
The symptoms caused by diabetic peripheral neuropathy (DPN) have severely impacted patients' quality of life. While plantamajoside (PMS) exhibits neuroprotective properties, its efficacy and molecular mechanisms against DPN are unexplored. This study first established a high glucose (HG)-induced in vitro model of DPN and investigated the neuroprotective effects of PMS on RSC96 cells. We next demonstrated the anti-apoptotic effects of PMS and NGF/TrkA pathway mediated neurotrophic effects. Finally, we established a DPN mouse model and confirmed the therapeutic effects of PMS on DPN mice through behavioural tests and pathological staining, while also assessing the impact of PMS on the NGF/TrkA pathway and apoptosis. Our results showed that, in HG-induced DPN models, PMS enhanced cell viability while reducing LDH activity. Transcriptomics results indicated that the Apoptosis and Neurotrophins signalling pathways were key pathways for PMS on DPN. PMS treatment reduced HG-induced RSC96 cell apoptosis while enhancing NGF levels and upregulating NGF/TrkA-related protein expression. However, this protection was abolished by TrkA inhibitor or NGF neutralising antibodies. In vivo experimental results showed that PMS improved the mechanical pain threshold, thermal pain reaction time, and nerve conduction velocity of DPN mice. PMS improved pathological damage to the sciatic nerve, enhanced the number of Nissl bodies, reduced TUNEL-positive expression, and upregulated NGF levels. Furthermore, PMS reduced apoptosis and elevated NGF/TrkA-related protein expression in the sciatic nerve of DPN mice. In conclusion, PMS alleviates DPN through activating the NGF/TrkA pathway and inhibiting apoptosis.
糖尿病周围神经病变（DPN）所引起的症状严重影响了患者的生活质量。虽然大车前苷（PMS）具有神经保护特性，但其针对DPN的疗效和分子机制尚未得到研究。本研究首先建立了高糖（HG）诱导的DPN体外模型，并研究了PMS对RSC96细胞的神经保护作用。接下来，我们证明了PMS的抗凋亡作用以及NGF/TrkA通路介导的神经营养作用。最后，我们建立了DPN小鼠模型，并通过行为测试和病理染色证实了PMS对DPN小鼠的治疗效果，同时还评估了PMS对NGF/TrkA通路和细胞凋亡的影响。我们的结果表明，在HG诱导的DPN模型中，PMS提高了细胞活力，同时降低了乳酸脱氢酶（LDH）活性。转录组学结果表明，凋亡和神经营养因子信号通路是PMS作用于DPN的关键通路。PMS处理可减少HG诱导的RSC96细胞凋亡，同时提高NGF水平并上调NGF/TrkA相关蛋白表达。然而，TrkA抑制剂或NGF中和抗体可消除这种保护作用。体内实验结果表明，PMS改善了DPN小鼠的机械痛阈、热痛反应时间和神经传导速度。PMS改善了坐骨神经的病理损伤，增加了尼氏体数量，减少了TUNEL阳性表达，并提高了NGF水平。此外，PMS减少了DPN小鼠坐骨神经中的细胞凋亡，并上调了NGF/TrkA相关蛋白表达。总之，PMS通过激活NGF/TrkA通路和抑制细胞凋亡来减轻DPN。
