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黄酮类化合物杨梅苷在小鼠持续性炎症性和神经性疼痛模型中的抗痛觉过敏特性。

Anti-allodynic property of flavonoid myricitrin in models of persistent inflammatory and neuropathic pain in mice.

作者信息

Meotti Flavia Carla, Missau Fabiana Cristina, Ferreira Juliano, Pizzolatti Moacir Geraldo, Mizuzaki Cristina, Nogueira Cristina Wayne, Santos Adair R S

机构信息

Departamento de Química, Universidade Federal de Santa Maria, 97110-000 Santa Maria, RS, Brazil.

出版信息

Biochem Pharmacol. 2006 Dec 15;72(12):1707-13. doi: 10.1016/j.bcp.2006.08.028. Epub 2006 Sep 10.

Abstract

The aim of the present study was to investigate the effects of myricitrin, a flavonoid with anti-inflammatory and antinociceptive action, upon persistent neuropathic and inflammatory pain. The neuropathic pain was caused by a partial ligation (2/3) of the sciatic nerve and the inflammatory pain was induced by an intraplantar (i.pl.) injection of 20 microL of complete Freund's adjuvant (CFA) in adult Swiss mice (25-35 g). Seven days after sciatic nerve constriction and 24 h after CFA i.pl. injection, mouse pain threshold was evaluated through tactile allodynia, using Von Frey Hair (VFH) filaments. Further analyses performed in CFA-injected mice were paw edema measurement, leukocytes infiltration, morphological changes and myeloperoxidase (MPO) enzyme activity. The intraperitoneal (i.p.) treatment with myricitrin (30 mg/kg) significantly decreased the paw withdrawal response in persistent neuropathic and inflammatory pain and decreased mouse paw edema. CFA injection increased 4-fold MPO activity and 27-fold the number of neutrophils in the mouse paw after 24 h. Myricitrin strongly reduced MPO activity, returning to basal levels; however, it did not reduce neutrophils migration. In addition, myricitrin treatment decreased morphological alterations to the epidermis and dermis papilar of mouse paw. Together these results indicate that myricitrin produces pronounced anti-allodynic and anti-edematogenic effects in two models of chronic pain in mice. Considering that few drugs are currently available for the treatment of chronic pain, the present results indicate that myricitrin might be potentially interesting in the development of new clinically relevant drugs for the management of this disorder.

摘要

本研究的目的是调查杨梅素(一种具有抗炎和镇痛作用的黄酮类化合物)对持续性神经性疼痛和炎性疼痛的影响。神经性疼痛由坐骨神经部分结扎(2/3)引起,炎性疼痛通过在成年瑞士小鼠(25 - 35克)足底注射20微升完全弗氏佐剂(CFA)诱导产生。坐骨神经缩窄7天后以及CFA足底注射24小时后,使用von Frey毛发(VFH)细丝通过触觉异常性疼痛评估小鼠疼痛阈值。对注射CFA的小鼠进行的进一步分析包括爪肿胀测量、白细胞浸润、形态学变化和髓过氧化物酶(MPO)酶活性。腹腔注射(i.p.)杨梅素(30毫克/千克)可显著降低持续性神经性疼痛和炎性疼痛中的爪退缩反应,并减轻小鼠爪肿胀。CFA注射24小时后,小鼠爪中的MPO活性增加了4倍,中性粒细胞数量增加了27倍。杨梅素强烈降低MPO活性,使其恢复到基础水平;然而,它并未减少中性粒细胞迁移。此外,杨梅素治疗减少了小鼠爪表皮和真皮乳头的形态学改变。这些结果共同表明,杨梅素在小鼠慢性疼痛的两种模型中产生了显著的抗异常性疼痛和抗水肿作用。鉴于目前可用于治疗慢性疼痛的药物很少,目前的结果表明,杨梅素在开发用于管理这种疾病的新的临床相关药物方面可能具有潜在的意义。

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