Department of Anesthesiology, The Changzheng Hospital, The Second Affiliated Hospital of Naval Medical University, Shanghai, China.
Department of Pharmacology and Zhejiang Key Lab of Pathophysiology, Ningbo University, Health Science Center, Ningbo, Zhejiang province, China.
Eur J Pharmacol. 2024 Sep 5;978:176749. doi: 10.1016/j.ejphar.2024.176749. Epub 2024 Jun 17.
A substantial proportion of diabetic patients suffer a debilitating and persistent pain state, known as peripheral painful neuropathy that necessitates improved therapy or antidote. Purpurin, a natural anthraquinone compound from Rubia tinctorum L., has been reported to possess antidepressant activity in preclinical studies. As antidepressants have been typically used as standard agents against persistent neuropathic pain, this study aimed to probe the effect of purpurin on neuropathic pain associated with streptozotocin-induced type 1 diabetes in male C57BL6J mice. The Hargreaves test and the von Frey test were used to assess the pain-like behaviors, shown as heat hyperalgesia and mechanical allodynia respectively. Chronic treatment of diabetic mice with purpurin not only ameliorated the established symptoms of heat hyperalgesia and mechanical allodynia, but also arrested the development of these pain states given preemptively at low doses. Although purpurin treatment hardly impacted on metabolic disturbance in diabetic mice, it ameliorated exacerbated oxidative stress in pain-associated tissues, improved mitochondrial bioenergetics in dorsal root ganglion neurons and restored nerve conduction velocity in sciatic nerves. Notably, the analgesic actions of purpurin were modified by pharmacologically manipulating redox status and mitochondrial bioenergetics. These findings unveil the analgesic activity of purpurin, an effect that is causally associated with its bioenergetics-enhancing and antioxidant effects, in mice with type 1 diabetes.
相当一部分糖尿病患者患有衰弱性和持续性疼痛状态，称为周围性疼痛性神经病，这需要改善治疗或解毒剂。茜草素是从茜草（Rubia tinctorum L.）中提取的天然蒽醌化合物，据报道在临床前研究中具有抗抑郁作用。由于抗抑郁药通常被用作治疗持续性神经病理性疼痛的标准药物，因此本研究旨在探讨茜草素对链脲佐菌素诱导的 1 型糖尿病雄性 C57BL6J 小鼠神经病理性疼痛的影响。使用 Hargreaves 测试和 von Frey 测试评估疼痛样行为，分别表现为热痛觉过敏和机械性痛觉过敏。茜草素慢性治疗糖尿病小鼠不仅改善了热痛觉过敏和机械性痛觉过敏的既定症状，而且在低剂量预先给药时还阻止了这些疼痛状态的发展。尽管茜草素治疗对糖尿病小鼠的代谢紊乱几乎没有影响，但它改善了与疼痛相关组织中加剧的氧化应激，改善了背根神经节神经元中的线粒体生物能，并恢复了坐骨神经中的神经传导速度。值得注意的是，茜草素的镇痛作用通过药理学操纵氧化还原状态和线粒体生物能来调节。这些发现揭示了茜草素在 1 型糖尿病小鼠中的镇痛活性，这种作用与其增强生物能和抗氧化作用有关。
