Pharmacology Department, Biological Sciences Sector, Federal University of Paraná, Mailbox: 19031, Curitiba, PR, CEP 81540-970, Brazil.
Chemistry Department, Federal University of Paraná, Curitiba, PR, Brazil.
Inflammopharmacology. 2024 Apr;32(2):1263-1275. doi: 10.1007/s10787-024-01444-9. Epub 2024 Mar 11.
This study evaluated the composition and the antinociceptive and anti-inflammatory activity of the crude extracts and two isolated compounds, anamarine (ANA) and 10-epi-olguine (eOL), obtained from the leaves of Cantinoa stricta (Lamiaceae). Crude ethanolic extract (EEt) and dichloromethane extract (DCM), selected based on NMR data, were submitted to pharmacological tests in male Swiss mice. The oral administration of EEt and DCM significantly reduced the second phase of formalin-induced nociception (60%), lipopolysaccharide (LPS)-induced mechanical hyperalgesia (90%), and carrageenan (Cg)-induced edema (25%). ANA and eOL, the major compounds in EEt and DCM extracts, administered orally or locally (in the paw), also reduced the LPS-induced mechanical hyperalgesia (Oral ID 1.9 and 3.9 mg/kg; Local ID 93.4 and 677.3 ng, respectively) without changing the thermal acute nociception or the motor performance of the animals. Local administration of ANA and eOL also reduced Cg-induced edema (40 and 23%, respectively). These isolated compounds did not change the mechanical hyperalgesia induced by tumor necrosis factor-α, interleukin-1β, prostaglandin E2, dibutyryl cyclic AMP, or forskolin but reversed the hyperalgesia induced by dopamine, epinephrine, and phorbol 12-myristate 13-acetate. The hyperalgesia induced by epinephrine was reversed in male but not in female mice, in which this response is not dependent on protein kinase C (PKC). These results suggest that C. stricta extracts possess antinociceptive and anti-inflammatory activity which is related to the presence of ANA and eOL. Differently from the known analgesics, these substances seem to exert their action mainly interfering with the sympathetic component of pain, possibly with PKC.
本研究评估了从堇叶碎米荠（唇形科）的叶子中获得的粗提取物和两种分离化合物，安纳明（ANA）和 10-表-奥古恩（eOL）的组成以及其镇痛和抗炎活性。根据 NMR 数据选择的粗乙醇提取物（EEt）和二氯甲烷提取物（DCM）在雄性瑞士小鼠中进行了药理测试。EEt 和 DCM 的口服给药显著减轻了福尔马林诱导的疼痛的第二阶段（60％），脂多糖（LPS）诱导的机械性痛觉过敏（90％）和角叉菜胶（Cg）诱导的水肿（25％）。ANA 和 eOL 是 EEt 和 DCM 提取物中的主要化合物，口服或局部（在脚上）给药也减轻了 LPS 诱导的机械性痛觉过敏（口服 ID 1.9 和 3.9mg/kg；局部 ID 93.4 和 677.3ng，分别），而不会改变动物的热急性痛觉或运动表现。局部给予 ANA 和 eOL 也减轻了 Cg 诱导的水肿（分别为 40％和 23％）。这些分离的化合物没有改变肿瘤坏死因子-α、白细胞介素-1β、前列腺素 E2、二丁酰环 AMP 或佛波醇 12-肉豆蔻酸 13-乙酸酯诱导的机械性痛觉过敏，但逆转了多巴胺、肾上腺素和佛波醇 12-肉豆蔻酸 13-乙酸酯诱导的痛觉过敏。肾上腺素诱导的痛觉过敏仅在雄性小鼠中被逆转，而在雌性小鼠中未被逆转，在雌性小鼠中，这种反应不依赖于蛋白激酶 C（PKC）。这些结果表明，堇叶碎米荠提取物具有镇痛和抗炎活性，这与 ANA 和 eOL 的存在有关。与已知的镇痛药不同，这些物质似乎主要通过干扰疼痛的交感成分来发挥作用，可能与 PKC 有关。
