Kulkarni Namrata Pramod, Vaidya Bhupesh, Narula Acharan S, Sharma Shyam Sunder
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Sector 67, Punjab 160062, India.
Narula Research Llc, 107 Boulder Bluff, Chapel Hill, North Carolina, NC 27516, USA.
Curr Neurovasc Res. 2022;19(3):293-302. doi: 10.2174/1567202619666220829104851.
Chemotherapy-induced peripheral neuropathy is a debilitating pain syndrome produced as a side effect of antineoplastic drugs like paclitaxel. Despite efforts, the currently available therapeutics suffer from serious drawbacks like unwanted side effects and poor efficacy and provide only symptomatic relief. Hence, there is a need to find new therapeutic alternatives for the treatment of chemotherapy-induced peripheral neuropathy.
The objective of this study was to explore the protective potential of caffeic acid phenethyl ester in paclitaxel-induced neuropathic pain.
We examined the effects of caffeic acid phenethyl ester by administering paclitaxel (2 mg/kg, intraperitoneal) to female Sprague Dawley rats on four alternate days to induce neuropathic pain, followed by the administration of caffeic acid phenethyl ester (10 and 30 mg/kg, intraperitoneally).
Rats that were administered paclitaxel showed a substantially diminished pain threshold and nerve functions after 28 days. A significantly increased protein expression of Wnt signalling protein (β-catenin), inflammatory marker (matrix metalloproteinase 2) and a decrease in endogenous antioxidant (nuclear factor erythroid 2-related factor 2) levels were found in paclitaxel administered rats in comparison to the naïve control group. Caffeic acid phenethyl ester (10 and 30 mg/kg, intraperitoneal) showed improvements in behavioural and nerve function parameters along with reduced expression of β-catenin, matrix metalloproteinase 2 and an increase in nuclear factor erythroid 2- related factor 2 protein expression.
The present study suggests that caffeic acid phenethyl ester attenuates chemotherapyinduced peripheral neuropathy via inhibition of β-catenin and matrix metalloproteinase 2 and increases nuclear factor erythroid 2-related factor 2 activation.
化疗引起的周围神经病变是一种使人衰弱的疼痛综合征，是由紫杉醇等抗肿瘤药物的副作用产生的。尽管人们做出了努力，但目前可用的治疗方法存在严重缺陷，如不良副作用和疗效不佳，且只能提供症状缓解。因此，需要寻找治疗化疗引起的周围神经病变的新治疗选择。
本研究的目的是探讨咖啡酸苯乙酯对紫杉醇诱导的神经性疼痛的保护潜力。
我们通过给雌性Sprague Dawley大鼠每隔一天腹腔注射紫杉醇（2mg/kg）以诱导神经性疼痛，随后腹腔注射咖啡酸苯乙酯（10mg/kg和30mg/kg），来研究咖啡酸苯乙酯的作用。
注射紫杉醇的大鼠在28天后疼痛阈值和神经功能显著降低。与未处理的对照组相比，注射紫杉醇的大鼠中Wnt信号蛋白（β-连环蛋白）、炎症标志物（基质金属蛋白酶2）的蛋白表达显著增加，内源性抗氧化剂（核因子红细胞2相关因子2）水平降低。咖啡酸苯乙酯（10mg/kg和30mg/kg，腹腔注射）显示行为和神经功能参数有所改善，同时β-连环蛋白、基质金属蛋白酶2的表达降低，核因子红细胞2相关因子2蛋白表达增加。
本研究表明，咖啡酸苯乙酯通过抑制β-连环蛋白和基质金属蛋白酶2，并增加核因子红细胞2相关因子2的激活，减轻化疗引起的周围神经病变。
