Hesperidin produces antinociceptive response and synergistic interaction with ketorolac in an arthritic gout-type pain in rats
Hesperidin produces antinociceptive response and synergistic interaction with ketorolac in an arthritic gout-type pain in rats
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DOI：
10.1016/j.pbb.2010.11.010
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发表时间：
2011-02-01
影响因子：
3.6
通讯作者：
Lopez-Munoz, Francisco J.
中科院分区：
文献类型：
--
作者：
Laura Martinez, Ana;Eva Gonzalez-Trujano, Ma;Lopez-Munoz, Francisco J.
橙皮苷在芸香科和唇形科植物中的浓度最高。在人类营养中，它有助于血管的完整性，饮食中的缺乏与异常毛细血管渗漏和疼痛有关。在本研究中，迷迭香属植物地上部分的乙醇提取物中的橙皮苷被鉴定为活性化合物，该提取物在大鼠疼痛诱导的功能障碍模型（PIFIR）中进行测试，作为与临床痛风中观察到的相似的炎症和慢性伤害感受的测定。橙皮苷产生剂量依赖性和显著性反应，ED 25 = 1666.72 mg/kg，相比之下，在PIFIR模型中，提取物的ED 25 = 302.90 mg/kg或参比药物酮咯酸的ED 25 = 0.47 mg/kg。虽然R.在阿片样物质拮抗剂纳洛酮（10 mg/kg，s.c.）和5 HT（1A）拮抗剂WAY 100635（0.12mg/kg，s.c.），橙皮苷反应不被纳洛酮（10 mg/kg）、WAY 100635（0.12 mg/kg）、荷包牡丹碱（1 mg/kg，s.c.）氟马西尼（10 mg/kg，i. p.）或咖啡因（1 mg/kg，s.c.）。然而，在存在辣椒平（10或20 mg/kg，皮下注射）的情况下，它会减少提示TRPV 1受体的参与，当橙皮苷显著降低辣椒素诱导的伤害性反应时，TRPV 1受体的参与得到加强。当抗伤害剂量的橙皮苷与酮咯酸结合时，也观察到协同相互作用，产生15种组合，主要是加性和超加性反应。这些结果为橙皮苷的抗伤害活性提供了证据，并证明了与酮咯酸联合使用时的协同反应，可能是通过TRPV 1受体的参与，表明其在疼痛治疗中的临床潜力。(C)2010年爱思唯尔公司All rights reserved.
Hesperidin occurs in greatest concentration in plants from the Rutaceae and Lamiaceae families. In human nutrition it contributes to the integrity of blood vessels and its deficiency in the diet has been linked to abnormal capillary leakiness as well as pain. In this study, the bioflavonoid hesperidin was identified as an active compound in an ethanol extract of the Rosmarinus officinalis aerial parts tested in the pain-induced functional impairment model in the rat (PIFIR) as an assay of inflammatory and chronic nociception similar to that observed in clinical gout. Hesperidin produced a dose-dependent and significant response with an ED25 = 1666.72 mg/kg in comparison to an ED25 = 302.90 mg/kg for the extract or an ED25 = 0.47 mg/kg for the reference drug ketorolac in the PIFIR model. Although the antinociceptive response of R. officinalis was reverted in presence of the opioid antagonist naloxone (10 mg/kg, s.c.) and the 5HT(1A) antagonist WAY100635 (0.12 mg/kg, s.c.), the hesperidin response was not modified by naloxone (10 mg/kg), WAY100635 (0.12 mg/kg), bicuculline (1 mg/kg, s.c.), flumazenil (10 mg/kg, i.p.) or caffeine (1 mg/kg, s.c.). Nevertheless, it was reduced in presence of capsazepine (10 or 20 mg/kg, s.c.) suggesting the participation of the TRPV1 receptor, which was reinforced when hesperidin significantly reduced the capsaicin-induced nociceptive response. A synergistic interaction was also observed when antinociceptive doses of hesperidin were combined with those of ketorolac producing 15 combinations mainly in additive and supra-additive responses. These results provide evidence for the antinociceptive activity of hesperidin and demonstrate synergistic response when combined with ketorolac, possibly by involvement of the TRPV1 receptor, suggesting their clinical potential in pain therapy. (C) 2010 Elsevier Inc. All rights reserved.