Department of Biomedical Science, Faculty of Medicine and Health Science, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.
Integrative Pharmacogenomics Institute (iPROMISE), Level 7, FF3, Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor, Malaysia.
Biomed Res Int. 2019 Aug 5;2019:6593125. doi: 10.1155/2019/6593125. eCollection 2019.
Methanolic extract of Lindau leaves (MECN) has been reported to exert antinociceptive activity. The present study aimed to elucidate the possible antinociceptive mechanisms of a lipid-soluble fraction of MECN, which was obtained after sequential extraction in petroleum ether. The petroleum ether fraction of (PECN), administered orally to mice, was (i) subjected to capsaicin-, glutamate-, phorbol 12-myristate 13-acetate-, bradykinin-induced nociception model; (ii) prechallenged (intraperitoneal (i.p.)) with 0.15 mg/kg yohimbine, 1 mg/kg pindolol, 3 mg/kg caffeine, 0.2 mg/kg haloperidol, or 10 mg/kg atropine, which were the respective antagonist of -adrenergic, -adrenergic, adenosinergic, dopaminergic, or muscarinic receptors; and (iii) prechallenged (i.p.) with 10 mg/kg glibenclamide, 0.04 mg/kg apamin, 0.02 mg/kg charybdotoxin, or 4 mg/kg tetraethylammonium chloride, which were the respective inhibitor of ATP sensitive-, small conductance Ca-activated-, large conductance Ca-activated-, or nonselective voltage-activated-K channel. Results obtained demonstrated that PECN (100, 250, and 500 mg/kg) significantly (P<0.05) inhibited all models of nociception described earlier. The antinociceptive activity of 500 mg/kg PECN was significantly (P<0.05) attenuated when prechallenged with all antagonists or K channel blockers. However, only pretreatment with apamin and charybdotoxin caused full inhibition of PECN-induced antinociception. The rest of the K channel blockers and all antagonists caused only partial inhibition of PECN antinociception, respectively. Analyses on PECN's phytoconstituents revealed the presence of antinociceptive-bearing bioactive compounds of volatile (i.e., derivatives of -tocopherol, -tocopherol, and lupeol) and nonvolatile (i.e., cinnamic acid) nature. In conclusion, PECN exerts a non-opioid-mediated antinociceptive activity involving mainly activation of adenosinergic and cholinergic receptors or small- and large-conductance Ca-activated-K channels.
林达叶的甲醇提取物（MECN）已被报道具有抗伤害感受活性。本研究旨在阐明 MECN 的脂溶性部分的可能的抗伤害感受机制，该部分是通过在石油醚中连续提取获得的。给予小鼠口服石油醚馏分（PECN），进行（i）辣椒素、谷氨酸、佛波醇 12-肉豆蔻酸 13-醋酸酯、缓激肽诱导的伤害感受模型；（ii）用 0.15 mg/kg 育亨宾、1 mg/kg 普萘洛尔、3 mg/kg 咖啡因、0.2 mg/kg 氟哌啶醇或 10 mg/kg 阿托品预先挑战（腹腔内（i.p.）），它们分别是 -肾上腺素能、-肾上腺素能、腺苷能、多巴胺能或毒蕈碱受体的拮抗剂；和（iii）用 10 mg/kg 格列本脲、0.04 mg/kg 阿帕米、0.02 mg/kg 沙蟾毒素或 4 mg/kg 四乙铵氯化物预先挑战（i.p.），它们分别是 ATP 敏感型、小电导 Ca 激活型、大电导 Ca 激活型或非选择性电压激活型-K 通道的抑制剂。结果表明，PECN（100、250 和 500mg/kg）显著（P<0.05）抑制了上述所有伤害感受模型。当用所有拮抗剂或 K 通道阻滞剂预先挑战时，500mg/kg PECN 的抗伤害感受活性显著（P<0.05）减弱。然而，只有用阿帕米和沙蟾毒素预处理才能完全抑制 PECN 诱导的抗伤害感受。其余的 K 通道阻滞剂和所有拮抗剂分别仅引起 PECN 抗伤害感受的部分抑制。对 PECN 的植物成分的分析表明存在具有镇痛作用的生物活性化合物，包括挥发性（即 -生育酚、-生育酚和羽扇豆醇的衍生物）和非挥发性（即肉桂酸）性质。总之，PECN 发挥非阿片类介导的抗伤害感受活性，主要涉及激活腺苷能和胆碱能受体或小电导和大电导 Ca 激活型-K 通道。
