Xu Jinlong, Zhao Qizhi, Wei Lei, Yang Yu, Xu Rui, Yu Nengjiang, Zhao Yimin
Department of Natural Product Chemistry, Beijing Institute of Pharmacology and Toxicology, Beijing, China.
PLoS One. 2015 Feb 6;10(2):e0117801. doi: 10.1371/journal.pone.0117801. eCollection 2015.
In traditional medicine, Bauhinia glauca subsp. hupehana has long been used as an analgesic agent in China. The aim of this study was to evaluate the antinociceptive activity of the ethanol extract of the aerial parts of B. glauca subsp. hupehana (BHE) in rats and its chemical fingerprint. The antinociceptive activity of BHE was assessed in mice using chemically and heat-induced pain models, such as the acetic acid-induced writhing, hot plate, tail-flick and glutamate tests. Naltrexone hydrochloride, a non-selective opioid receptor antagonist, was utilized to determine the involvement of the opioid system. In addition to this, the involvements of the cGMP and ATP-sensitive K+ channel pathways were also detected using methylene blue and glibenclamide. The oral administration of BHE (at doses of 50, 100 and 200 mg/kg) produced significant and dose-related inhibitions in both the chemically and heat-induced pain models. Interestingly, in the abdominal constriction test, when the dose of BHE was increased to 800 mg/kg (p.o., n = 10), the inhibition rate was 100%. The antinociceptive mechanism may involve the cGMP pathway and ATP sensitive K+ channel pathway. The central antinociceptive effect was not antagonized by naltrexone. One phenolic acid, one lignin and five flavonoids were isolated from BHE. The antinociceptive activity of BHE was most likely due to the presence of the flavonoids. The acute toxicity results showed that BHE was safe at a high dose (2 g/kg, p.o.). The current investigation demonstrates that B. glauca subsp. hupehana is a potential candidate for the development of novel, non-opioid, analgesic phytomedicines.
在传统医学中,湖北羊蹄甲长期以来在中国被用作镇痛剂。本研究的目的是评估湖北羊蹄甲地上部分乙醇提取物(BHE)在大鼠中的抗伤害感受活性及其化学指纹图谱。使用化学和热诱导疼痛模型,如醋酸诱导扭体、热板、甩尾和谷氨酸试验,在小鼠中评估BHE的抗伤害感受活性。盐酸纳曲酮,一种非选择性阿片受体拮抗剂,用于确定阿片系统的参与情况。除此之外,还使用亚甲蓝和格列本脲检测cGMP和ATP敏感性钾通道途径的参与情况。口服BHE(剂量为50、100和200mg/kg)在化学和热诱导疼痛模型中均产生了显著的剂量相关抑制作用。有趣的是,在腹部收缩试验中,当BHE剂量增加到800mg/kg(口服,n = 10)时,抑制率为100%。抗伤害感受机制可能涉及cGMP途径和ATP敏感性钾通道途径。中枢抗伤害感受作用未被纳曲酮拮抗。从BHE中分离出一种酚酸、一种木质素和五种黄酮类化合物。BHE的抗伤害感受活性很可能归因于黄酮类化合物的存在。急性毒性结果表明,BHE在高剂量(2g/kg,口服)时是安全的。目前的研究表明,湖北羊蹄甲是开发新型非阿片类镇痛植物药的潜在候选者。