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平见柠檬(变种)在慢性轻度应激诱导的抑郁小鼠模型中调节肠-脑轴。

Hirami lemon ( var. ) modulates the gut-brain axis in a chronic mild stress-induced depression mouse model.

作者信息

Tsai Po-Heng, Wu Pei-Chen, Li Hui-Ru, Senthil Kumar K J, Wang Sheng-Yang

机构信息

Ph.D. Program in Microbial Genomics, National Chung Hsing University, Taichung, Taiwan and Academia Sinica, Taipei, Taiwan.

Department of Forestry, National Chung Hsing University, Taichung, Taiwan.

出版信息

Food Funct. 2023 Aug 14;14(16):7535-7549. doi: 10.1039/d3fo01301d.

DOI:10.1039/d3fo01301d
PMID:37526032
Abstract

var. , commonly known as Hirami lemon, is a native citrus species found in Taiwan and Okinawa islands of Japan. While several species are known to possess antidepressant activity by modulating the gut microbiota, the antidepressant effect of Hirami lemon and its underlying mechanisms have not been thoroughly investigated. In this study, we explored the potential antidepressant efficacy of the fruit extract (CD) and the essential oil (CDE) from Hirami lemon peel using a chronic mild stress (CMS)-induced mouse model and analyzed the association of gut microbiome changes. Our findings revealed that mice subjected to CMS exhibited anxiety- and depression-like behaviors as assessed by elevated plus-maze and forced swimming tests, respectively. Significantly, oral administration of CDE and CD notably reversed CMS-induced depression- and anxiety-like behaviors in CMS-induced mice. Moreover, compared to the non-stressed group, CMS significantly altered the gut microbiome, characterized by highly diverse bacterial communities, reduced Bacteroidetes, and increased Firmicutes. However, oral administration of CDE and CD restored gut microbiota dysbiosis. We also performed a qualitative analysis of CD and CDE using UPLC-MS and GC-MS, respectively. The CD contained 25 compounds, of which 3 were polymethoxy flavones and flavanones. Three major compounds, nobiletin, tangeretin and hesperidin, accounted for 56.88% of the total relative peak area. In contrast, the CDE contained 11 terpenoids, of which 8 were identified as major compounds, with D-limonene (45.71%) being the most abundant, followed by γ-terpinene (34.65%), linalool (6.46%), -cymene (2.57%), α-terpineol (2.04%), α-pinene (1.89%), α-terpinolene (1.46%), and β-pinene (1.16%), accounting for 95.94% of the total oil. In conclusion, our study demonstrated the potential of Hirami lemon as a source of natural antidepressant agents for the prevention and treatment of major depressive disorders.

摘要

变种,通常被称为平成柠檬,是一种原产于台湾和日本冲绳群岛的柑橘属物种。虽然已知几种物种通过调节肠道微生物群具有抗抑郁活性,但平成柠檬的抗抑郁作用及其潜在机制尚未得到充分研究。在本研究中,我们使用慢性轻度应激(CMS)诱导的小鼠模型探索了平成柠檬果皮的果实提取物(CD)和精油(CDE)的潜在抗抑郁功效,并分析了肠道微生物群变化的关联。我们的研究结果表明,通过高架十字迷宫和强迫游泳试验评估,接受CMS的小鼠分别表现出焦虑样和抑郁样行为。值得注意的是,口服CDE和CD显著逆转了CMS诱导的小鼠的抑郁样和焦虑样行为。此外,与非应激组相比,CMS显著改变了肠道微生物群,其特征是细菌群落高度多样化、拟杆菌减少和厚壁菌增加。然而,口服CDE和CD恢复了肠道微生物群失调。我们还分别使用超高效液相色谱-质谱联用仪(UPLC-MS)和气相色谱-质谱联用仪(GC-MS)对CD和CDE进行了定性分析。CD含有25种化合物,其中3种是多甲氧基黄酮和黄烷酮。三种主要化合物,川陈皮素、橘红素和橙皮苷,占总相对峰面积的56.88%。相比之下,CDE含有11种萜类化合物,其中8种被鉴定为主要化合物,D-柠檬烯(45.71%)含量最高,其次是γ-萜品烯(34.65%)、芳樟醇(6.46%)、对伞花烃(2.57%)、α-松油醇(2.04%)、α-蒎烯(1.89%)、α-萜品烯(1.46%)和β-蒎烯(1.16%),占总油的95.94%。总之,我们的研究证明了平成柠檬作为预防和治疗重度抑郁症的天然抗抑郁剂来源的潜力。

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