Laboratory Animal Science and Technology Center, College of Pharmacy, College of Science and Technology, Jiangxi University of Traditional Chinese Medicine, 1688 Meiling Road, Nanchang, 330004, PR China.
Laboratory Animal Science and Technology Center, College of Pharmacy, College of Science and Technology, Jiangxi University of Traditional Chinese Medicine, 1688 Meiling Road, Nanchang, 330004, PR China; State Key Laboratory of Natural Medicines, Department of Pharmacognosy, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, PR China.
J Ethnopharmacol. 2021 Feb 10;266:113426. doi: 10.1016/j.jep.2020.113426. Epub 2020 Sep 29.
In traditional Chinese medicine, the fruit of Schisandra chinensis (Turcz.) Baill (SC) is used to treat various nervous system diseases, such as dysphoria, anxiety, insomnia and many dreams. It is worthy to be noted that wine processed Schisandra chinensis (WSC) has been applied in clinic for thousands of years.
This study aimed to investigate the possible mechanism and related metabolism of SC and WSC ameliorating anxiety behavior through modulating gut microbiota.
The ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) was used for the quality control of chemical components in SC and WSC. Chronic unpredictable stress procedure (CUSP)-induced anxiety rats were administrated with SC and WSC via gavage for five weeks. An untargeted UPLC/LTQ-Orbitrap MS metabolomic analysis of plasma was conducted to understand the effects of long-term intake of WSC and SC extracts on anxious rats. 16S rRNA microbial sequencing technology was applied to investigate gut microbiota structure. Expression of GPR81, TNF-α, S1PR2 as well as molecules in cAMP pathway was assayed by immunohistochemistry staining, RT-qPCR, or Western blot, respectively.
12 compounds were identified using UPLC-QTOF-MS technology, all of which are lignans. Results demonstrate that the amounts of 6-O-Benzoylgomisin O, Schisandrin, Gomisin D, Schizandrin A, Gomisin T, Schizandrin B, Schisandrin C were higher in wine-processed samples than in raw samples. Furthermore, both SC and WSC significantly ameliorated anxiety- and depression-like behavior and lipid metabolism dysfunction and attenuated hippocampal neuritis in anxiety rats. After WSC treatment, the structure and composition of gut microbiota in anxiety rats changed significantly, and gut microbiota derivatives lactate level was significantly lower in the plasma and feces. WSC treatment help restore gut microbial ecosystem dysbiosis and reverse the changes in Lachnospiraceae, Lactobacillus, Alloprevotella, and Bacteroidales in anxiety rat. In addition, the expression of liver GPR81 was decreased, and the molecules in cAMP pathway were increased in SC and WSC-treated anxiety rat.
Raw and wine processed Schisandra chinensis treatment improved anxiety- and depression-like behavior through modulating gut microbiota derivatives in association with GPR81 receptor-mediated lipid metabolism pathway. And WSC has more exhibition than SC.
在中国传统医学中，五味子（SC）的果实用于治疗各种神经系统疾病，如烦躁不安、焦虑、失眠和多梦。值得注意的是，酒制五味子（WSC）已在临床上应用了数千年。
本研究旨在通过调节肠道微生物群，探讨 SC 和 WSC 改善焦虑行为的可能机制及相关代谢物。
采用超高效液相色谱-四极杆飞行时间质谱联用技术（UPLC-QTOF-MS）对 SC 和 WSC 中的化学成分进行质量控制。采用慢性不可预测应激程序（CUSP）诱导焦虑大鼠，通过灌胃给予 SC 和 WSC 五周。采用非靶向 UPLC/LTQ-Orbitrap MS 代谢组学分析血浆，了解长期摄入 WSC 和 SC 提取物对焦虑大鼠的影响。应用 16S rRNA 微生物测序技术研究肠道微生物群结构。采用免疫组织化学染色、RT-qPCR 或 Western blot 分别测定 GPR81、TNF-α、S1PR2 以及 cAMP 通路中分子的表达。
采用 UPLC-QTOF-MS 技术鉴定出 12 种化合物，均为木脂素。结果表明，6-O-苯甲酰戈米辛 O、五味子酯甲、五味子丙素、五味子甲素、戈米辛 T、五味子乙素、五味子 C 的含量在酒制样品中高于生样品。此外，SC 和 WSC 均能显著改善焦虑和抑郁样行为、脂质代谢紊乱，并减轻焦虑大鼠海马神经炎。WSC 治疗后，焦虑大鼠肠道微生物群结构和组成发生显著变化，血浆和粪便中乳酸水平显著降低。WSC 治疗有助于恢复肠道微生物生态失调，并逆转焦虑大鼠中lachnospiraceae、乳杆菌、alloprevotella 和 bacteroidales 的变化。此外，SC 和 WSC 治疗的焦虑大鼠肝 GPR81 表达降低，cAMP 通路中的分子增加。
生品和酒制品五味子治疗可通过调节与 GPR81 受体介导的脂质代谢途径相关的肠道微生物群衍生物改善焦虑和抑郁样行为，且 WSC 的作用优于 SC。
