Antinociceptive Properties of the Hydroalcoholic Extract and the Flavonoid Rutin Obtained from Polygala paniculata L. in Mice
Antinociceptive Properties of the Hydroalcoholic Extract and the Flavonoid Rutin Obtained from Polygala paniculata L. in Mice
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DOI：
10.1111/j.1742-7843.2008.00365.x
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发表时间：
2009-04-01
影响因子：
3.1
通讯作者：
Santos, Adair R. S.
中科院分区：
文献类型：
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作者：
Lapa, Fernanda da R.;Gadotti, Vinicius M.;Santos, Adair R. S.
本研究考察了远志水醇提取物在小鼠化学和热行为疼痛模型中的镇痛作用。采用化学方法评价水醇提取物的抗伤害作用（乙酸，福尔马林，辣椒素，肉桂醛和谷氨酸试验）和热（甩尾和热板试验）疼痛模型或在顶盖内施用兴奋性氨基酸受体谷氨酸和细胞因子如白细胞介素-1 β的离子型和代谢型激动剂后的咬行为（IL-1 β）和肿瘤坏死因子-α（TNF-α）。当口服给药时，水醇提取物（0.001-10 mg/kg）对乙酸诱导的内脏痛产生有效的剂量依赖性抑制。在福尔马林试验中，水醇提取物（口服0.0001-0.1 mg/kg）还对福尔马林诱导的舔体的早期（神经性疼痛）和晚期（炎性疼痛）阶段产生显著抑制。然而，与福尔马林试验的后期阶段相比，它更有效。辣椒素诱导的伤害性感受也在仅1.0 mg/kg口服剂量下降低。水醇提取物在0.01、0.1和1.0 mg/kg口服剂量下显著降低肉桂醚诱导的伤害性感受。此外，水醇提取物（口服0.001-1.0 mg/kg）对谷氨酸诱导的疼痛产生显著的剂量依赖性抑制。然而，只有从圆锥花科植物中分离的芸香苷（而不是phebalosin或aurapten）通过腹腔注射给小鼠，对谷氨酸诱导的疼痛产生了剂量相关的抑制作用。此外，水醇提取物（口服0.1-100 mg/kg）在甩尾试验中没有效果。另一方面，在热板试验中，以10 mg/kg的剂量口服水醇提取物导致反应潜伏期显著增加。在谷氨酸盐试验中，水醇提取物（0.1 mg/kg口服）的抗伤害作用不受L-精氨酸（一氧化氮前体，600 mg/kg）和纳洛酮（阿片受体拮抗剂，1 mg/kg）腹膜内给药的影响。也不与非特异性作用如肌肉松弛或镇静相关。此外，口服水醇提取物对鞘内注射谷氨酸、N-甲基-d-天冬氨酸（NMDA）、IL-1 β和TNF-α诱导的疼痛相关行为产生了很大的抑制作用，但对α-氨基-3-羟基-5-甲基-异恶唑-4-丙酸（AMPA）、红藻氨酸或反式-1-氨基-1.3-环戊二羧酸（trans-ACPD）诱导的疼痛相关行为没有抑制作用。总之，我们的研究结果表明，抑制多巴胺能离子型受体，可能是本研究中使用的化学疼痛模型中报道的来自P. paniculata的水醇提取物的抗伤害性作用的原因。
The present study examined the antinociceptive effects of a hydroalcoholic extract of Polygala paniculata in chemical and thermal behavioural models of pain in mice. The antinociceptive effects of hydroalcoholic extract was evaluated in chemical (acetic-acid, formalin, capsaicin, cinnamaldehyde and glutamate tests) and thermal (tail-flick and hot-plate test) models of pain or by biting behaviour following intratecal administration of both ionotropic and metabotropic agonists of excitatory amino acids receptors glutamate and cytokines such as interleukin-1 beta (IL-1 beta) and tumour necrosis factor-alpha (TNF-alpha) in mice. When given orally, hydroalcoholic extract (0.001-10 mg/kg), produced potent and dose-dependent inhibition of acetic acid-induced visceral pain. In the formalin test, the hydroalcoholic extract (0.0001-0.1 mg/kg orally) also caused significant inhibition of both the early (neurogenic pain) and the late (inflammatory pain) phases of formalin-induced licking. However, it was more potent and efficacious in relation to the late phase of the formalin test. The capsaicin-induced nociception was also reduced at a dose of only 1.0 mg/kg orally. The hydroalcoholic extract significantly reduced the cinnamaldehyde-induced nociception at doses of 0.01, 0.1 and 1.0 mg/kg orally. Moreover, the hydroalcoholic extract (0.001-1.0 mg/kg orally) caused significant and dose-dependent inhibition of glutamate-induced pain. However, only rutin, but not phebalosin or aurapten, isolated from P. paniculata, administered intraperitoneally to mice, produced dose-related inhibition of glutamate-induced pain. Furthermore, the hydroalcoholic extract (0.1-100 mg/kg orally) had no effect in the tail-flick test. On the other hand, the hydroalcoholic extract caused a significant increase in the latency to response at a dose of 10 mg/kg orally, in the hot-plate test. The hydroalcoholic extract (0.1 mg/kg orally) antinociception, in the glutamate test, was neither affected by intraperitoenal treatment of animals with l-arginine (precursor of nitric oxide, 600 mg/kg) and naloxone (opioid receptor antagonist, 1 mg/kg.) nor associated with non-specific effects such as muscle relaxation or sedation. In addition, oral administration of hydroalcoholic extract produced a great inhibition of the pain-related behaviours induced by intrathecal injection of glutamate, N-methyl-d-aspartate (NMDA), IL-1 beta and TNF-alpha, but not by alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA), kainate or trans-1-amino-1.3-cyclopentanediocarboxylic acid (trans-ACPD). Together, our results suggest that inhibition of glutamatergic ionotropic receptors, may account for the antinociceptive action reported for the hydroalcoholic extract from P. paniculata in models of chemical pain used in this study.