Zamani Kimia, Fakhri Sajad, Kiani Amir, Abbaszadeh Fatemeh, Farzaei Mohammad Hosein
Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, 6734667149, Iran.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Feb 6. doi: 10.1007/s00210-025-03842-4.
Neuropathic pain is a chronic type of pain caused by damage or dysfunction in the nervous system. It can be quite bothersome and often doesn't well respond to common painkillers. Among natural compounds, rutin (Rut) stands out for its remarkable antioxidant, and anti-inflammatory properties. In this research, our objective is to investigate the impact of Rut on an animal model of chronic constriction injury (CCI). A total of 54 adult Wistar rats were divided randomly into nine separate groups. Groups included sham, CCI, gabapentin (GBP, 100 mg/kg), Rut (10, 25 mg/kg), flumazenil (FLU, 0.5 mg/kg), naloxone (NAL, 0.1 mg/kg), Rut (10 mg/kg) + FLU (0.5 mg/kg), and Rut (10 mg/kg) + NAL (0.1 mg/kg). The aforementioned drug injection (intraperitoneal, i.p.) and sensorimotor behavioral tests were performed on days 1, 3, 5, 7, 9, 11, and 14. Biochemical (e.g., nitrite, catalase, glutathione), zymography (matrix-metalloproteinase 2 and 9), and histopathological tests were performed on day 14 after surgery. The findings demonstrated that Rut administration effectively alleviated symptoms of allodynia/hyperalgesia, and improved locomotor activity following CCI. Additionally, Rut administration resulted in increased catalase and glutathione activity, while reducing serum nitrite levels, as well as matrix metalloproteinase 2 and 9 activity. Additionally, histological results indicated that Rut improved sciatic nerve regeneration. Since the aforementioned effects of Rut were reversed by using opioid and benzodiazepine receptor antagonists (i.e., NAL and FLU, respectively), the receptors' involvement was revealed in the anti-neuropathic effects of Rut. In conclusion, Rut emerged as a potentially effective candidate for treating neuropathic pain and improving motor function by increasing antioxidant mediators, suppressing inflammation, and activating opioid/benzodiazepine receptors.
神经性疼痛是一种由神经系统损伤或功能障碍引起的慢性疼痛类型。它可能相当令人困扰，并且通常对普通止痛药反应不佳。在天然化合物中，芦丁（Rut）因其显著的抗氧化和抗炎特性而脱颖而出。在本研究中，我们的目的是研究芦丁对慢性压迫性损伤（CCI）动物模型的影响。总共54只成年Wistar大鼠被随机分为9个单独的组。这些组包括假手术组、CCI组、加巴喷丁（GBP，100mg/kg）组、芦丁（10、25mg/kg）组、氟马西尼（FLU，0.5mg/kg）组、纳洛酮（NAL，0.1mg/kg）组、芦丁（10mg/kg）+氟马西尼（0.5mg/kg）组以及芦丁（10mg/kg）+纳洛酮（0.1mg/kg）组。在第1、3、5、7、9、11和14天进行上述药物注射（腹腔内，i.p.）和感觉运动行为测试。在手术后第14天进行生化测试（例如亚硝酸盐、过氧化氢酶、谷胱甘肽）、酶谱分析（基质金属蛋白酶2和9）以及组织病理学测试。研究结果表明，给予芦丁可有效减轻CCI后的异常性疼痛/痛觉过敏症状，并改善运动活动。此外，给予芦丁可导致过氧化氢酶和谷胱甘肽活性增加，同时降低血清亚硝酸盐水平以及基质金属蛋白酶2和9的活性。另外，组织学结果表明芦丁可改善坐骨神经再生。由于芦丁的上述作用分别被阿片类和苯二氮䓬受体拮抗剂（即纳洛酮和氟马西尼）逆转，因此揭示了这些受体参与了芦丁的抗神经性疼痛作用。总之，芦丁通过增加抗氧化介质、抑制炎症以及激活阿片类/苯二氮䓬受体，成为治疗神经性疼痛和改善运动功能的潜在有效候选药物。
