ABSTRACT Chrysin, a natural flavonoid, is the main ingredient of many medicinal plants, which shows potent pharmacological properties. In the present study, the antinociceptive effects of chrysin were examined in ICR mice. Chrysin orally administered at the doses of from 10 to 100 mg/kg exerted the reductions of formalin-induced pain behaviors observed during the second phase in the formalin test in a dose-dependent manner. In addition, the antinociceptive effect of chrysin was further characterized in streptozotocin-induced diabetic neuropathy model. Oral administration chrysin caused reversals of decreased pain threshold observed in diabetic-induced peripheral neuropathy model. Intraperitoneally (i.p.) pretreatment with naloxone (a classic opioid receptor antagonist), but not yohimbine (an antagonist of α2-adrenergic receptors) or methysergide (an antagonist of serotonergic receptors), effectively reversed chrysin-induced antinociceptive effect in the formalin test. Moreover, chrysin caused a reduction of formalin-induced up-regulated spinal p-CREB level, which was also reversed by i.t. pretreated naloxone. Finally, chrysin also suppressed the increase of the spinal p-CREB level induced by diabetic neuropathy. Our results suggest that chrysin shows an antinociceptive property in formalin-induced pain and diabetic neuropathy models. In addition, spinal opioid receptors and CREB protein appear to mediate chrysin-induced antinociception in the formalin-induced pain model.

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白杨素在糖尿病神经病变和福尔马林诱发的疼痛模型中的镇痛作用

摘要白杨素是一种天然黄酮类化合物，是许多药用植物的主要成分，具有强大的药理作用。在本研究中，在 ICR 小鼠中检查了白杨素的镇痛作用。以 10 至 100 mg/kg 的剂量口服白杨素以剂量依赖性方式降低福尔马林试验第二阶段期间观察到的福尔马林诱发的疼痛行为。此外，白杨素的镇痛作用在链脲佐菌素诱导的糖尿病神经病变模型中得到进一步表征。在糖尿病诱导的周围神经病变模型中观察到的口服白杨素导致疼痛阈值降低的逆转。用纳洛酮（一种经典的阿片受体拮抗剂）进行腹膜内 (ip) 预处理，但在福尔马林试验中，育亨宾（α2-肾上腺素能受体的拮抗剂）或美西麦角（5-羟色胺能受体的拮抗剂）不能有效逆转白杨素诱导的镇痛作用。此外，白杨素导致福尔马林诱导的上调脊髓 p-CREB ​​水平降低，这也被它预处理的纳洛酮逆转。最后，白杨素还抑制了由糖尿病神经病变引起的脊髓 p-CREB ​​水平的增加。我们的结果表明，白杨素在福尔马林引起的疼痛和糖尿病神经病变模型中显示出镇痛特性。此外，脊髓阿片受体和 CREB ​​蛋白似乎在福尔马林诱导的疼痛模型中介导白杨素诱导的镇痛作用。白杨素导致福尔马林诱导的上调脊髓 p-CREB ​​水平降低，这也被它预处理的纳洛酮逆转。最后，白杨素还抑制了由糖尿病神经病变引起的脊髓 p-CREB ​​水平的增加。我们的结果表明，白杨素在福尔马林引起的疼痛和糖尿病神经病变模型中显示出镇痛特性。此外，脊髓阿片受体和 CREB ​​蛋白似乎在福尔马林诱导的疼痛模型中介导白杨素诱导的镇痛作用。白杨素导致福尔马林诱导的上调脊髓 p-CREB ​​水平降低，这也被它预处理的纳洛酮逆转。最后，白杨素还抑制了由糖尿病神经病变引起的脊髓 p-CREB ​​水平的增加。我们的结果表明，白杨素在福尔马林引起的疼痛和糖尿病神经病变模型中显示出镇痛特性。此外，脊髓阿片受体和 CREB ​​蛋白似乎在福尔马林诱导的疼痛模型中介导白杨素诱导的镇痛作用。