Mendes G L, Santos A R, Campos M M, Tratsk K S, Yunes R A, Cechinel Filho V, Calixto J B
Department of Pharmacology, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
Life Sci. 1998;63(5):369-81. doi: 10.1016/s0024-3205(98)00285-9.
This study analyses the anti-hyperalgesic properties of the hydroalcoholic extract (HE) and the sesquiterpene polygodial isolated from the barks of Drymis winteri (Winteraceae). The HE (10 to 60 mg kg(-1), i.p. or 100 to 600 mg kg(-1), p.o.), 4 h prior, produced significant inhibition of abdominal constrictions caused by i.p. injection of acetic acid, kaolin and zymosan in mice. The mean ID50s were: 21.4, 33.7 and 36.6 mg kg(-1); 173.0, 123.0 and 366.0 mg kg(-1), by i.p. and by oral route, respectively. This effect lasted for up to 8 h. The HE at the same range of doses produced dose-related inhibition of both phases of the formalin-induced licking. The calculated mean ID50s values for the early phase were: 26.1 and 43.0 mg kg(-1), while for the late phase they were 7.3 and 72.7 mg kg(-1), respectively, when given by i.p. and by oral route. The HE (10 to 60 mg kg(-1), i.p. or 25 to 200 mg kg(-1), p.o.), 4 h prior, produced significant inhibition of capsaicin-induced neurogenic pain with mean ID50 values of 18.0 and 68.0 mg kg(-1), respectively. The HE (3 to 100 mg kg(-1), p.o., 1 h) inhibited in a graded manner, the hyperalgesia induced by bradykinin (3 nmol/paw) or substance P (10 nmol/paw) in rat paw, with mean ED50 values of 54.5 and 53.7 mg kg(-1), respectively. However, the HE did not affect the hyperalgesia induced by carrageenan or PGE2. When assessed in the hot-plate test, the HE (200 mg kg(-1), p.o.) was inactive. Naloxone (1 mg kg(-1), i.p.) significantly reversed the antinociceptive effects caused by either morphine (5 mg kg(-1), s.c.) or by HE (60 mg kg(-1), i.p.). Polygodial (0.1 to 10 mg kg(-1), i.p.) produced significant inhibition of acetic acid, kaolin and zymosan-induced writhing in mice, being about 14 to 27-fold more potent than the HE at the ID50 level. Together these data provide support for a long-lasting anti-hyperalgesic property for the active principle(s) present in the barks of D. winteri when assessed in several models of inflammatory or neurogenic pain. Its actions involve, at least in part, an interaction with opioid pathway through a naloxone-sensitive mechanism, seeming not to be related with a non-specific peripheral or central depressant actions. Finally, the sesquiterpene polygodial isolated from this plant, appears to be mainly responsible for the anti-hyperalgesic properties of the extract.
本研究分析了从冬木（林仙科）树皮中分离出的水醇提取物（HE）和倍半萜多香树素的抗痛觉过敏特性。提前4小时腹腔注射HE（10至60毫克/千克）或口服（100至600毫克/千克），可显著抑制小鼠腹腔注射醋酸、高岭土和酵母聚糖引起的腹部收缩。腹腔注射和口服的半数抑制剂量（ID50）平均值分别为：21.4、33.7和36.6毫克/千克；173.0、123.0和366.0毫克/千克。这种作用可持续长达8小时。相同剂量范围的HE对福尔马林诱导舔舐的两个阶段均产生剂量相关的抑制作用。腹腔注射和口服时，早期阶段计算出的平均ID50值分别为：26.1和43.0毫克/千克，而晚期阶段分别为7.3和72.7毫克/千克。提前4小时腹腔注射HE（10至60毫克/千克）或口服（25至200毫克/千克），可显著抑制辣椒素诱导的神经源性疼痛，平均ID50值分别为18.0和68.0毫克/千克。口服HE（3至100毫克/千克，1小时）可分级抑制缓激肽（3纳摩尔/爪）或P物质（10纳摩尔/爪）诱导的大鼠爪部痛觉过敏，平均半数有效剂量（ED50）值分别为54.5和53.7毫克/千克。然而，HE不影响角叉菜胶或前列腺素E2诱导的痛觉过敏。在热板试验中评估时，口服HE（200毫克/千克）无活性。纳洛酮（1毫克/千克，腹腔注射）可显著逆转吗啡（5毫克/千克，皮下注射）或HE（60毫克/千克，腹腔注射）引起的镇痛作用。多香树素（0.1至10毫克/千克，腹腔注射）可显著抑制小鼠醋酸、高岭土和酵母聚糖诱导的扭体反应，在ID50水平上比HE强约14至27倍。这些数据共同支持了冬木树皮中存在的活性成分在多种炎症性或神经源性疼痛模型中具有持久的抗痛觉过敏特性。其作用至少部分涉及通过纳洛酮敏感机制与阿片类途径相互作用，似乎与非特异性外周或中枢抑制作用无关。最后，从该植物中分离出的倍半萜多香树素似乎是提取物抗痛觉过敏特性的主要原因。
