Laboratory of Cardiovascular Physiology and Pharmacology, Federal University of Bahia, Salvador, Bahia, Brazil.
Laboratory of Neuroscience, Federal University of Bahia, Salvador, Bahia, Brazil.
Biochem Pharmacol. 2018 May;151:38-46. doi: 10.1016/j.bcp.2018.02.014. Epub 2018 Feb 16.
Linalool (LIN) is a monoterpene alcohol present in some aromatic medicinal plants with biological activities that can impact cardiovascular diseases. This chemical class is highly volatile and β-cyclodextrin (β-CD) has been employed to improve the pharmacological properties of monoterpenes. Thus, the aim of this study was to evaluate the cardiovascular effects of LIN free focusing on the antihypertensive properties of this monoterpene and to study whether LIN, complexed in β-cyclodextrin (LIN-βCD) is able to improve the pharmacological activity of LIN. Spontaneously hypertensive rats (SHR) were randomly divided into 5 groups, each treated daily for 21 days, in the following manner: group 1 (vehicle solution); group 2 (captopril; 30 mg/kg/day); group 3 (LIN; 100 mg/kg/day); group 4 (LIN; 50 mg/kg/day) and group 5 (LIN/β-CD; 50 mg/kg/day). Daily body weight measurements were conducted and mean arterial pressure and heart rate were measured every 5 days. The mesenteric artery from treated animals was tested for phenylephrine and sodium nitroprusside (SNP) sensitivity. The SHR treated with vehicle demonstrated progressive increase in mean arterial pressure and captopril, a positive control, induced a significant decrease. After 21 days of treatment, the blood pressure of the SHR treated by (-)-LIN (100 mg/kg) was significantly reduced. In addition, various important cardiovascular parameters improved, including: the treatment with LIN prevented the development of cardiac hypertrophy, increased levels of the anti-inflammatory cytokine (IL-10), increased vasodilator responsiveness and reduced sensitivity to the sympathetic agonist. Furthermore, the inclusion complex containing LIN in β-CD produced a higher antihypertensive profile when compared with uncomplexed form. Taking together, our results suggested that LIN shown a potential antihypertensive effect and β-CD may be an important tool to improve the cardiovascular activity of LIN and other water-insoluble compounds.
芳樟醇（LIN）是某些芳香药用植物中存在的单萜醇，具有可影响心血管疾病的生物活性。此类化学物质具有高度挥发性，β-环糊精（β-CD）已被用于改善单萜的药理特性。因此，本研究的目的是评估 LIN 的心血管作用，重点关注这种单萜的降压特性，并研究 LIN 与β-环糊精（LIN-βCD）形成复合物是否能够提高 LIN 的药理活性。自发性高血压大鼠（SHR）随机分为 5 组，每组每天接受治疗 21 天，具体如下：第 1 组（载体溶液）；第 2 组（卡托普利；30mg/kg/天）；第 3 组（LIN；100mg/kg/天）；第 4 组（LIN；50mg/kg/天）和第 5 组（LIN/β-CD；50mg/kg/天）。每天测量体重，每 5 天测量一次平均动脉压和心率。对接受治疗的动物的肠系膜动脉进行苯肾上腺素和硝普钠（SNP）敏感性测试。用载体处理的 SHR 显示平均动脉压逐渐升高，阳性对照卡托普利可显著降低血压。经过 21 天的治疗，（-）-LIN（100mg/kg）治疗的 SHR 血压明显降低。此外，各种重要的心血管参数得到改善，包括：LIN 治疗可预防心肌肥厚的发展，增加抗炎细胞因子（IL-10）水平，增加血管舒张反应性，降低对交感神经激动剂的敏感性。此外，与未络合的形式相比，含有 LIN 的β-CD 包合物表现出更高的降压特性。综上所述，我们的结果表明，LIN 具有潜在的降压作用，β-CD 可能是提高 LIN 和其他水溶性差的化合物心血管活性的重要工具。
