Dougnon Godfried, Ito Michiho
Department of Pharmacognosy, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.
Pharmaceuticals (Basel). 2021 Jul 6;14(7):651. doi: 10.3390/ph14070651.
(L.) R.M.King & H.Rob. essential oil (COEO) was investigated for its sedative activity in mice. The results showed that COEO significantly reduced mice locomotor activity and the most efficient concentrations were 0.04 and 0.00004 mg/cage (volume of the cage 61.2L). Analysis of chemical composition of the oil indicated that caryophyllene oxide (43.75%) was the major compound and bioactivity-guided fractionation of the oil was performed to isolate the compound responsible for activity. The data clearly identified sesquiterpene caryophyllene oxide as the compound inducing COEO sedative activity and it was effective in decreasing mice locomotor activity by 56% and 57% at 0.0004 and 0.04 mg/cage, respectively. In order to understand the action mechanisms, caryophyllene oxide was tested for its effects on the central nervous system (CNS) by using a caffeine pre-excited mice test and a pentobarbital sleeping-induced test in mice. The results showed that caryophyllene oxide is a potent CNS depressant. Nevertheless, it fails to potentiate the effects of pentobarbital on the GABAergic system, nor did flumazenil, a GABA receptor antagonist, reversed its effects. It was especially interesting to note that -caryophyllene, the precursor of caryophyllene oxide, demonstrated a similar pattern of sedative activity, and the present work further extends actual knowledge on these naturally occurring sesquiterpenes. The findings in this study reveal the new activity of caryophyllene oxide as an innovative way to manage sleep and CNS-related disorders, and demonstrates a satisfactory effect of two interesting sesquiterpene compounds on the CNS.
对唇萼薄荷（L.）精油（COEO）在小鼠中的镇静活性进行了研究。结果表明，COEO显著降低了小鼠的运动活性，最有效的浓度为0.04和0.00004毫克/笼（笼子体积61.2升）。对该精油的化学成分分析表明，氧化石竹烯（43.75%）是主要成分，并对该精油进行了生物活性导向分级分离以分离出具有活性的化合物。数据明确确定倍半萜氧化石竹烯是诱导COEO镇静活性的化合物，它在0.0004和0.04毫克/笼时分别有效降低小鼠运动活性56%和57%。为了了解其作用机制，通过咖啡因预激发小鼠试验和小鼠戊巴比妥诱导睡眠试验测试了氧化石竹烯对中枢神经系统（CNS）的影响。结果表明，氧化石竹烯是一种有效的中枢神经系统抑制剂。然而，它不能增强戊巴比妥对GABA能系统的作用，GABA受体拮抗剂氟马西尼也不能逆转其作用。特别有趣的是，氧化石竹烯的前体β-石竹烯表现出类似的镇静活性模式，并且本研究进一步扩展了对这些天然存在的倍半萜的实际认识。本研究结果揭示了氧化石竹烯作为一种管理睡眠和中枢神经系统相关疾病的创新方法的新活性，并证明了两种有趣的倍半萜化合物对中枢神经系统具有令人满意的效果。
