Journal of ethnopharmacology · 2025
Citrus medica L. essential oil improves anxiety-like behaviors accompanied by fatigue through α7-nAChR receptor-mediated neuroprotection effects.
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Yang Yanyan, Song Yonggui, Xu Weize, Ai Zhifu, Zhu Genhua, Yang Ming, Zheng Qin, Xu Huanhua, Liu Yali, Ping Yuhui, Su Dan
Аннотация
ETHNOPHARMACOLOGICAL RELEVANCE: Citrus medica L. has been cultivated in China for over two thousand years, with the effects of soothing the liver, regulating qi. Studies have shown that it can relieve anxiety. Its combination with other traditional Chinese medicines has been widely used in clinical practice assist in the treatment of anxiety and depression. The essential oil rich in peel is important active substance of Citrus medica L. A large number of studies have confirmed that essential oils are commonly used to relieve pain, psychological stress and induce relaxation. However, there are currently no studies on the effects of Citrus medica L. essential oil (CEO) on anxiety.
AIM OF THE STUDY: Anxiety has become the most common mental illness worldwide, so effective and diverse prevention and control methods are urgently needed. The main objective of this study is to evaluate the therapeutic effect and optimal administration route of CEO on anxiety caused by different susceptibility factors, and to further explore its potential mechanism for improving anxiety, providing scientific guidance for the application of CEO.
MATERIALS AND METHODS: Induce anxiety models caused by fatigue or stress, and use animal behavior as an indicator to evaluate the CEO. To illustrate the underlying mechanisms of anti-anxiety effect of CEO, histological examination, immunofluorescence staining and Western Blot were carried out.
RESULTS: The results showed that the safer inhalation administration was more effective. Compared with the stress-induced anxiety model, CEO has a more obvious effect on fatigue-induced anxiety. After CEO administration, the frequency, time, and movement distance of fatigue-type anxious mice in Open Field Test (OFT) increased significantly. During Elevated Plus Maze Test (EPM), the mice spent more time and have more entry in the open arm. Further research found that CEO can significantly increase cerebral blood flow, recover damaged neurons in the hippocampus. RNA-seq analysis investigated that CEO can significantly improve gene expression in the hippocampus of fatigue accompanied anxiety mice. The underlying mechanism is significantly related to cholinergic system pathways. Further research found that the alpha-7 nicotinic acetylcholine receptor (α7-nAChR) in anxious mice was down-regulated, accompanied by decreased activation of its downstream ERK/CREB. Inhaling essential oil improved fatigue-induced anxiety by reversing this phenomenon.
CONCLUSIONS: The results demonstrated that CEO have a significant anti-anxiety effect, especially fatigue induced anxiety. Our research results verify the accuracy and effectiveness of symptomatic treatment strategies for anxiety caused by different susceptibility factors, and provide scientific guidance for the rational use of CEO.
AIM OF THE STUDY: Anxiety has become the most common mental illness worldwide, so effective and diverse prevention and control methods are urgently needed. The main objective of this study is to evaluate the therapeutic effect and optimal administration route of CEO on anxiety caused by different susceptibility factors, and to further explore its potential mechanism for improving anxiety, providing scientific guidance for the application of CEO.
MATERIALS AND METHODS: Induce anxiety models caused by fatigue or stress, and use animal behavior as an indicator to evaluate the CEO. To illustrate the underlying mechanisms of anti-anxiety effect of CEO, histological examination, immunofluorescence staining and Western Blot were carried out.
RESULTS: The results showed that the safer inhalation administration was more effective. Compared with the stress-induced anxiety model, CEO has a more obvious effect on fatigue-induced anxiety. After CEO administration, the frequency, time, and movement distance of fatigue-type anxious mice in Open Field Test (OFT) increased significantly. During Elevated Plus Maze Test (EPM), the mice spent more time and have more entry in the open arm. Further research found that CEO can significantly increase cerebral blood flow, recover damaged neurons in the hippocampus. RNA-seq analysis investigated that CEO can significantly improve gene expression in the hippocampus of fatigue accompanied anxiety mice. The underlying mechanism is significantly related to cholinergic system pathways. Further research found that the alpha-7 nicotinic acetylcholine receptor (α7-nAChR) in anxious mice was down-regulated, accompanied by decreased activation of its downstream ERK/CREB. Inhaling essential oil improved fatigue-induced anxiety by reversing this phenomenon.
CONCLUSIONS: The results demonstrated that CEO have a significant anti-anxiety effect, especially fatigue induced anxiety. Our research results verify the accuracy and effectiveness of symptomatic treatment strategies for anxiety caused by different susceptibility factors, and provide scientific guidance for the rational use of CEO.