Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea; Department of Pharmacy, Abdul Wali Khan University, Mardan, Pakistan.
J Ethnopharmacol. 2014 Mar 28;152(3):478-86. doi: 10.1016/j.jep.2014.01.028. Epub 2014 Feb 2.
Artemisia capillaris has widespread traditional and pharmacological applications such as analgesic, anti-inflammatory, anti-pyretic, enhance immunity and anti-tumor activity properties. To evaluate the pharmacological activities of this plant, capillarisin, one of the potent constituent of Artemisia capillaris was studied based on anti-hyperalgesic and anti-allodynic effects with detailed mechanism. It can be assumed that measurement of anti-nociceptive effects of capillarisin is one of the parameter for the evaluation of this herb. Capillarisin has extensive pharmacological properties and has been considered to have promising ant-inflammatory and anti-nociceptive activities. The aim of the current study is to investigate the effect of capillarisin and underlying molecular mechanisms of action in preventing acute and subchronic inflammatory pain.
The inflammatory pain was induced after 40 min or 1h of administration of vehicle, 70% EtOH extract of Artemisia capillaris (100mg/kg) or capillarisin (20 and 80 mg/kg) by intraplantar (i.p.l.) injections of CFA and carrageenan in ICR mice, respectively. Mechanical hyperalgesia and allodynia were evaluated in both acute and subchronic models. Further analysis was performed in CFA-induced mice exploring various molecular and signaling pathways such as NF-κB, AP-1, and ERK-CREB involved in the persistent pain sensations.
In acute model, mechanical hyperalgesia and allodynia were evaluated after every 2h until 6h of CFA and after 4h of carrageenan injections. Whereas, in subchronic inflammatory pain model, mechanical hyperalgesia and paw edema were measured after 4h of CFA injection and every day after 4h of daily treatment until 5 days with interval of day four in order to assess the tolerance effect of capillarisin. Further analysis was performed in CFA-induced mice exploring various molecular and signaling pathways such as NF-κB, AP-1 and ERK-CREB involved in the persistent of pain sensations. Pre-treatment of capillarisin strongly inhibited NF-κB mediated genes (iNOS, COX-2), involved in pain. The plasma leading nitrite production was significantly reduced by capillarisin. Moreover, i.p. administration of capillarisin markedly suppressed the adenosine 5׳-triphosphate (ATP) in plasma and substance P in CFA-induced paw tissue.
The present study indicates that capillarisin possessed promising anti-hyperalgesic and anti-allodynic effects through the inhibition of various inflammatory pain signaling, suggesting that capillarisin constitutes a significant component for the treatment of inflammatory pain.
ETHNOPHARMACOLOGICAL 相关性：青蒿具有广泛的传统和药理学应用，如镇痛、抗炎、解热、增强免疫力和抗肿瘤活性。为了评估这种植物的药理学活性，基于青蒿素的抗痛觉过敏和抗感觉异常作用及其详细机制，研究了青蒿素作为青蒿素的有效成分之一。可以假设，青蒿素的抗伤害感受作用的测量是评估这种草药的参数之一。青蒿素有广泛的药理作用，并被认为具有有希望的抗炎和抗伤害感受活性。本研究的目的是研究 capillarisin 的作用及其在预防急性和亚慢性炎症性疼痛中的作用机制。
通过腹腔内（i.p.l.）注射 CFA 和角叉菜胶，分别在 ICR 小鼠中诱导 40 分钟或 1 小时后给予载体、青蒿 70%乙醇提取物（100mg/kg）或 capillarisin（20 和 80mg/kg），分别诱导炎症性疼痛。在急性和亚慢性模型中评估机械性痛觉过敏和感觉异常。在 CFA 诱导的小鼠中进一步进行分析，探讨参与持续性疼痛感觉的各种分子和信号通路，如 NF-κB、AP-1 和 ERK-CREB。
在急性模型中，在 CFA 后每 2 小时至 6 小时评估机械性痛觉过敏和感觉异常，在角叉菜胶注射后 4 小时评估机械性痛觉过敏和感觉异常。然而，在亚慢性炎症性疼痛模型中，在 CFA 注射后 4 小时测量机械性痛觉过敏和爪肿胀，并在每天 4 小时治疗后每天测量，直到第 5 天，第 4 天间隔一天，以评估 capillarisin 的耐受性。在 CFA 诱导的小鼠中进一步进行分析，探讨参与持续性疼痛感觉的各种分子和信号通路，如 NF-κB、AP-1 和 ERK-CREB。预处理 capillarisin 强烈抑制参与疼痛的 NF-κB 介导基因（iNOS、COX-2）。capillarisin 显著减少血浆中 leading nitrite 的产生。此外，腹腔内给予 capillarisin 可显著抑制 CFA 诱导的爪组织中三磷酸腺苷（ATP）和 P 物质的产生。
本研究表明，capillarisin 通过抑制多种炎症性疼痛信号，具有有希望的抗痛觉过敏和抗感觉异常作用，提示 capillarisin 是治疗炎症性疼痛的重要组成部分。
