Formulated Curcumin Prevents Paclitaxel-Induced Peripheral Neuropathy through Reduction in Neuroinflammation by Modulation of α7 Nicotinic Acetylcholine Receptors.
Formulated Curcumin Prevents Paclitaxel-Induced Peripheral Neuropathy through Reduction in Neuroinflammation by Modulation of α7 Nicotinic Acetylcholine Receptors.
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配方姜黄素通过调节α7烟碱乙酰胆碱受体减少神经炎症来预防紫杉醇诱导的周围神经病变。
DOI：
10.3390/pharmaceutics14061296
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发表时间：
2022-06-17
期刊：
影响因子：
5.4
通讯作者：
Damaj, M. Imad
中科院分区：
文献类型：
--
作者：
Caillaud, Martial;Thompson, Danielle;Toma, Wisam;White, Alyssa;Mann, Jared;Roberts, Jane L.;Bigbee, John W.;Gewirtz, David A.;Damaj, M. Imad
紫杉醇广泛用于治疗各种类型的实体恶性肿瘤。紫杉醇诱导的周围神经病变（PIPN）通常以患者的灼痛、寒冷和机械性异常性疼痛为特征。目前，缺乏针对PIPN的特异性药物治疗。姜黄素是姜黄的多酚，具有抗氧化、抗炎和神经保护作用，最近已显示出缓解各种周围神经病变的功效。在这里，我们第一次测试了1.5%饮食姜黄素和Meriva（姜黄素的卵磷脂制剂）在预防C57 BL/6 J小鼠中PIPN发展方面的治疗效果。姜黄素或Meriva治疗在注射紫杉醇前一周开始，并在整个研究期间持续（21天）。机械和冷敏感性以及运动/动机进行了测试，分别由冯弗雷，丙酮，和轮运行测试。此外，感觉神经动作电位（SNAP）幅度尾神经电刺激，坐骨神经的电子显微镜，并在DRG和脊髓的炎症蛋白定量进行了测量。有趣的是，在Meriva饮食的脊髓中观察到的姜黄素浓度高于姜黄素饮食。我们的研究结果表明，紫杉醇诱导的机械超敏反应部分防止姜黄素饮食，但完全防止Meriva。Urcumin饮食和Meriva饮食都完全防止了冷超敏反应，在紫杉醇治疗的小鼠中观察到的坐骨神经中SNAP振幅的降低和线粒体病理学的减少。Meriva饮食也可以预防紫杉醇诱导的脊髓炎症。此外，在紫杉醇治疗小鼠的脊髓中，也观察到Meriva饮食的α7 nAChRs mRNA增加，这是已知的抗炎作用。α7 nAChR拮抗剂和α7 nAChR KO小鼠的使用首次在体内表明，姜黄素在周围神经病变中的抗炎作用是由这些受体介导的。本研究中的结果代表了对姜黄素体内作用机制的理解的重要进展。总之，我们的结果显示了姜黄素在预防PIPN发展方面的治疗潜力，并进一步证实了α7 nAChR在姜黄素抗炎作用中的作用。
Paclitaxel is widely used in the treatment of various types of solid malignancies. Paclitaxel-induced peripheral neuropathy (PIPN) is often characterized by burning pain, cold, and mechanical allodynia in patients. Currently, specific pharmacological treatments against PIPN are lacking. Curcumin, a polyphenol of Curcuma longa, shows antioxidant, anti-inflammatory, and neuroprotective effects and has recently shown efficacy in the mitigation of various peripheral neuropathies. Here, we tested, for the first time, the therapeutic effect of 1.5% dietary curcumin and Meriva (a lecithin formulation of curcumin) in preventing the development of PIPN in C57BL/6J mice. Curcumin or Meriva treatment was initiated one week before injection of paclitaxel and continued throughout the study (21 days). Mechanical and cold sensitivity as well as locomotion/motivation were tested by the von Frey, acetone, and wheel-running tests, respectively. Additionally, sensory-nerve-action-potential (SNAP) amplitude by caudal-nerve electrical stimulation, electronic microscopy of the sciatic nerve, and inflammatory-protein quantification in DRG and the spinal cord were measured. Interestingly, a higher concentration of curcumin was observed in the spinal cord with the Meriva diet than the curcumin diet. Our results showed that paclitaxel-induced mechanical hypersensitivity was partially prevented by the curcumin diet but completely prevented by Meriva. Both the urcumin diet and the Meriva diet completely prevented cold hypersensitivity, the reduction in SNAP amplitude and reduced mitochondrial pathology in sciatic nerves observed in paclitaxel-treated mice. Paclitaxel-induced inflammation in the spinal cord was also prevented by the Meriva diet. In addition, an increase in α7 nAChRs mRNA, known for its anti-inflammatory effects, was also observed in the spinal cord with the Meriva diet in paclitaxel-treated mice. The use of the α7 nAChR antagonist and α7 nAChR KO mice showed, for the first time in vivo, that the anti-inflammatory effects of curcumin in peripheral neuropathy were mediated by these receptors. The results presented in this study represent an important advance in the understanding of the mechanism of action of curcumin in vivo. Taken together, our results show the therapeutic potential of curcumin in preventing the development of PIPN and further confirms the role of α7 nAChRs in the anti-inflammatory effects of curcumin.
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影响因子：
5.2
作者：
Caillaud M;Patel NH;Toma W;White A;Thompson D;Mann J;Tran TH;Roberts JL;Poklis JL;Bigbee JW;Fang X;Gewirtz DA;Damaj MI
通讯作者：
Damaj MI
DOI：
10.1523/jneurosci.3795-08.2008
发表时间：
2008-12-24
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Binshtok AM;Wang H;Zimmermann K;Amaya F;Vardeh D;Shi L;Brenner GJ;Ji RR;Bean BP;Woolf CJ;Samad TA
通讯作者：
Samad TA
影响因子：
5.1
作者：
Greeshma, N.;Prasanth, K. G.;Balaji, Bhaskar
通讯作者：
Balaji, Bhaskar
影响因子：
2.4
作者：
Agthong, Sithiporn;Kaewsema, Athitaya;Charoensub, Thuntawat
通讯作者：
Charoensub, Thuntawat
影响因子：
7.2
作者：
Chandran, Binu;Goel, Ajay
通讯作者：
Goel, Ajay