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Effects of isopulegol in acute nociception in mice: Possible involvement of muscarinic receptors, opioid system and l-arginine/NO/cGMP pathway
Chemico-Biological Interactions ( IF 5.1 ) Pub Date : 2018-07-24 , DOI: 10.1016/j.cbi.2018.07.019
Deyna Francélia Andrade Próspero , Antonio Carlos Reis Filho , Celyane Alves Piauilino , Everton Moraes Lopes , Damião Pergentino de Sousa , Fernanda Regina de Castro Almeida

Previous studies have shown that isopulegol has anxiolytic, anticonvulsant, gastro-protective and antioxidant activities in rodents, but until now there are no studies showing activity of isopulegol in animal models of nociception and inflammation. The objective of this study was to evaluate the antinociceptive effect of isopulegol and to propose possible mechanisms involved in its effects observed in mice. Groups of male and female Swiss mice (20–35 g, n = 5–8) were used in this test under the authorization of Ethics Committee on Animal Experimentation (CEEA/UFPI N° 82/2014). In order to evaluate the antinociceptive activity of isopulegol, nociception was induced using formalin test, capsaicin and glutamate in hind paw licking model, followed by the investigation of the involvement of opioid mechanisms, K + ATP channels, muscarinic, L arginine-nitric oxide and cGMP. The oral administration of isopulegol showed antinociceptive effect in both phases of the formalin test at doses from 0.78 to 25 mg/kg (first phase) and 1.56–25 mg/kg (second phase) and also produced significant results before capsaicin test at doses from 1.56 to 12.5 mg/kg and glutamate test at doses from 3.12 to 6.25 mg/kg with a dose-dependent effect. The antinociception activity of isopulegol was inhibited in the presence of naloxone (2 mg / kg, ip), glibenclamide (3 mg/kg, ip), atropine (1 mg/kg, ip), l-arginine (600 mg/kg, ip) and methylene blue (20 mg/kg, ip). The results suggested that acute antinociceptive action of opioid isopulegol seems to be related to the K + ATP channels system, through the involvement of muscarinic receptors, inhibiting nitric oxide and cGMP.



中文翻译:

异胡薄荷醇在小鼠急性伤害感受中的作用:毒蕈碱受体,阿片类药物系统和l-精氨酸/ NO / cGMP途径可能参与

以前的研究表明,异戊醇在啮齿动物中具有抗焦虑,抗惊厥,保护胃和抗氧化的作用,但到目前为止,尚无研究表明异戊醇在伤害感受和炎症的动物模型中具有活性。这项研究的目的是评估异胡薄荷醇的抗伤害感受作用,并提出在小鼠中观察到的影响其作用的可能机制。根据动物实验伦理委员会(CEEA / UFPI N°82/2014)的授权,将成组的雄性和雌性瑞士小鼠(20–35 g,n = 5–8)用于该测试。为了评估异胡薄荷醇的镇痛活性,在后爪舔食模型中使用福尔马林试验,辣椒素和谷氨酸诱导了伤害感受,然后研究了阿片类药物机制,K + ATP通道,毒蕈碱,精氨酸一氧化氮和cGMP。在福尔马林试验的两个阶段中,口服异异薄荷醇在0.78至25 mg / kg(第一阶段)和1.56–25 mg / kg(第二阶段)的剂量下均显示出抗伤害作用,并且在辣椒素试验前的剂量为1.56至12.5 mg / kg的谷氨酸盐测试浓度为3.12至6.25 mg / kg,具有剂量依赖性。在纳洛酮(2 mg / kg,ip),格列本脲(3 mg / kg,ip),阿托品(1 mg / kg,ip),5 mg / kg,谷氨酸测试浓度为3.12至6.25 mg / kg,具有剂量依赖性。在纳洛酮(2 mg / kg,ip),格列本脲(3 mg / kg,ip),阿托品(1 mg / kg,ip),5 mg / kg,谷氨酸测试浓度为3.12至6.25 mg / kg,具有剂量依赖性。在纳洛酮(2 mg / kg,ip),格列本脲(3 mg / kg,ip),阿托品(1 mg / kg,ip),1-精氨酸(600mg / kg,ip)和亚甲蓝(20mg / kg,ip)。结果表明,阿片类异胡薄荷醇的急性镇痛作用似乎通过参与毒蕈碱受体,抑制一氧化氮和cGMP与K + ATP通道系统有关。

更新日期:2018-07-24
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