Freitas Cristina Setim, Baggio Cristiane Hatsuko, Dos Santos Ana Cristina, Mayer Bárbara, Twardowschy André, Luiz Ana Paula, Marcon Rodrigo, Soldi Cristian, Pizzolatti Moacir G, Dos Santos Elide Pereira, Marques Maria Consuelo Andrade, Santos Adair R S
Department of Pharmacology, Sector of Biological Sciences, Federal University of Paraná, Curitiba, PR, Brazil.
Basic Clin Pharmacol Toxicol. 2009 Apr;104(4):285-92. doi: 10.1111/j.1742-7843.2008.00367.x. Epub 2009 Mar 5.
The present study assessed the possible antinociceptive action of the hydroalcoholic extract, fractions and pure compounds obtained from the aerial parts of Baccharis illinita DC (Asteraceae) in behavioural models of chemical nociception in mice. The hydroalcoholic extract and fractions (hexane and aqueous but not EtOAc fraction) obtained from B. illinita (30-1000 mg/kg orally) produced a dose-related inhibition of the acetic acid-induced nociceptive response. However, the hexane fraction was more potent than the hydroalcoholic extract and the aqueous fraction. The hexane fraction derivatives baurenol, alpha-spinasterol and oleanolic acid (0.00001-10 mg/kg intraperitoneally) also caused potent inhibition of acetic acid-induced pain. The hexane fraction (300-1000 mg/kg orally) produced inhibition of both phases of formalin-induced pain. Moreover, the hexane fraction (30-600 mg/kg orally) also caused a dose-dependent inhibition of glutamate-induced pain. Nevertheless, the hexane fraction only at the dose of 300 mg/kg orally, produced partial inhibition of the paw oedema caused by carrageenan. Furthermore, the hexane fraction (300 mg/kg orally) caused inhibition of the nociceptive response induced by intrathecal injection of N-methyl-d-aspartic acid, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, tumour necrosis factor-alpha and interleukin-1beta. In contrast, the hexane fraction did not affect the biting response induced by the metabotropic or ionotropic glutamatergic receptor agonist (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid and kainate, respectively. In addition, the antinociception caused by the hexane fraction (300 mg/kg orally) in the acetic acid test was not affected by intraperitoneal treatment of mice with naloxone (a non-selective opioid receptor antagonist). The precise mechanism responsible for the antinociceptive effect of the hexane fraction remains unclear, but appears to be partly associated with an inhibition of glutamatergic transmission and an inhibition of pathways dependent on pro-inflammatory cytokines. Finally, baurenol, alpha-spinasterol and oleanolic acid have an important role in the antinociceptive effects of the hexane fraction. Moreover, the antinociceptive action demonstrated in the present study supports the ethnomedical uses of this plant.
本研究评估了从伊利尼塔酒神菊（菊科）地上部分获得的水醇提取物、馏分和纯化合物在小鼠化学伤害感受行为模型中可能的抗伤害感受作用。从伊利尼塔酒神菊获得的水醇提取物和馏分（己烷和水相馏分，但乙酸乙酯馏分除外，口服剂量为30 - 1000 mg/kg）对乙酸诱导的伤害感受反应产生了剂量相关的抑制作用。然而，己烷馏分比水醇提取物和水相馏分更有效。己烷馏分衍生物贝壳杉烯醇、α-菠菜甾醇和齐墩果酸（腹腔注射剂量为0.00001 - 10 mg/kg）也对乙酸诱导的疼痛产生了显著抑制作用。己烷馏分（口服剂量为300 - 1000 mg/kg）对福尔马林诱导的疼痛的两个阶段均产生了抑制作用。此外，己烷馏分（口服剂量为30 - 600 mg/kg）也对谷氨酸诱导的疼痛产生了剂量依赖性抑制作用。然而，己烷馏分仅在口服剂量为300 mg/kg时，对角叉菜胶引起的爪肿胀产生了部分抑制作用。此外，己烷馏分（口服剂量为300 mg/kg）对鞘内注射N-甲基-D-天冬氨酸、α-氨基-3-羟基-5-甲基-4-异恶唑丙酸、肿瘤坏死因子-α和白细胞介素-1β诱导的伤害感受反应产生了抑制作用。相比之下，己烷馏分分别不影响由代谢型或离子型谷氨酸能受体激动剂（±）-1-氨基环戊烷-反式-1,3-二羧酸和海藻酸诱导的咬噬反应。此外，己烷馏分（口服剂量为300 mg/kg）在乙酸试验中引起的抗伤害感受作用不受用纳洛酮（一种非选择性阿片受体拮抗剂）对小鼠进行腹腔注射治疗的影响。负责己烷馏分抗伤害感受作用的确切机制尚不清楚，但似乎部分与谷氨酸能传递的抑制以及对依赖促炎细胞因子的途径的抑制有关。最后，贝壳杉烯醇、α-菠菜甾醇和齐墩果酸在己烷馏分的抗伤害感受作用中起重要作用。此外，本研究中证明的抗伤害感受作用支持了这种植物的民族医学用途。
