羟基积雪草酸的镇痛活性及其作用机制研究

Anti-nociceptive effect and mechanism of madecassic acid

目前对积雪草的功效成分研究主要集中在三萜皂苷类成分,对其他成分的药理活性研究较少。本研究采用小鼠醋酸扭体实验、热板法实验和福尔马林实验,对羟基积雪草酸的镇痛活性进行探究。实验分为对照组、阳性药阿司匹林组和低(10 mg/kg)、中(20 mg/kg)、高(40 mg/kg)剂量的羟基积雪草酸(MA)组。同时,还采用阿片受体阻断实验,辣椒素和谷氨酸诱导的小鼠舔爪实验,对其镇痛机制进行研究。结果显示:MA在醋酸扭体实验和福尔马林实验的Ⅱ阶段表现出显著的镇痛活性;在醋酸扭体实验和福尔马林实验中,MA的镇痛活性没有被纳洛酮明显减弱;中、高剂量的MA均能有效地减轻由辣椒素所引起的疼痛,抑制率分别为29.5%和64.4%,还能有效地缩减由谷氨酸所引起的舔爪时间,抑制率分别为30.9%和56.1%。研究结果表明:MA可通过作用于外周神经系统发挥较好的镇痛作用;该化合物产生的镇痛活性可能涉及谷氨酸能系统和TRPV1的调节,但不涉及阿片能系统。

To date,the investigation of the functional composition of Centella asiatica(L.)Urban has been mainly focused on the triterpenoid saponins,with little research on the other compositions.The acetic acidinduced writhing,Eddy's hot plate and formalin tests were employed to investigate the anti-nociceptive effects of madecassic acid(MA).The experiment was divided into normal control group,acetylsalicylic acid(ASA)group,and the MA groups of low(10 mg/kg),medium(20 mg/kg)and high(40 mg/kg)dosage.Meanwhile,the antinociceptive effect of MA on the acetic acid and formalin-induced nociceptive models in the absence and presence of NAL(naloxone hydrochloride)was evaluated.To have an insight into the anti-nociceptive mechanisms of MA,the capsaicin-and glutamate-induced paw licking tests were also employed to evaluate the involvement of the vanilloid and glutamatergic systems,respectively.Results showed that MA exhibited good anti-nociceptive activity in the acetic acid-induced writhing test and the second phase of formalin test;the anti-nociceptive effect of MA in both the acetic acid and formalin-induced nociception was not effectively removed by NAL;MA(20 mg/kg and 40 mg/kg)effectively reduced the duration of biting/licking the capsaicin-injected paw with inhibition rates of 29.5%and 64.4%,respectively;MA(20 mg/kg and 40 mg/kg)distinctly shortened the time spent in biting/licking the glutamate-injected paw by 30.9%and 56.1%,respectively.In summary,MA induces significant peripheral anti-nociceptive effect,and the anti-nociceptive activities probably involve the modulation of glutamatergic systems and vanilloid systems(TRPV1)instead of the opioidergic system.