加味逍遥丸通过神经递质调节、抗炎抗氧化及肠道菌群调控改善大鼠的抑郁样行为  

Jiawei Xiaoyao Pills improves depression-like behavior in rats by regulating neurotransmitters,inhibiting inflammation and oxidation and modulating intestinal flora

作　　者：刘莹 李柏睿 李永财 常禄博 王娇 杨琳 颜永刚[1,2] 屈凯 刘继平 张岗[1] 沈霞 LIU Ying;LI Borui;LI Yongcai;CHANG Lubo;WANG Jiao;YANG Lin;YAN Yonggang;QV Kai;LIU Jiping;ZHANG Gang;SHEN Xia(School of Pharmacy,Shaanxi University of Chinese Medicine,Xixian New Area 712046,China;Qinling Chinese Herbal Medicine Application and Development Engineering Technology Research Center,Xixian New Area 712046,China;Shaanxi Provincial Hospital of Traditional Chinese Medicine,Xi'an 710003,China;Key Laboratory of Pharmacodynamic Mechanism and Material Basis of Traditional Chinese Medicine,Shaanxi Provincial Administration of Traditional Chinese Medicine,Xixian New Area 712046,China)

机构地区：[1]陕西中医药大学药学院,陕西西咸新区712046 [2]陕西省秦岭中草药应用开发工程技术研究中心,陕西西咸新区712046 [3]陕西省中医医院,陕西西安710003 [4]陕西省中医药管理局中药药效机制与物质基础重点研究室,陕西西咸新区712046

出　　处：《南方医科大学学报》2025年第2期347-358,共12页Journal of Southern Medical University

基　　金：陕西省自然科学基础研究计划项目(2022JM-538);重点产业创新链(群)-社会发展领域(2024SF-ZDCYL-03-04);陕西省中医药中青年科技骨干人才项目(11610000MB29656749/2020-00894)。

摘　　要：目的基于网络药理学、代谢组学和16srDNA探究加味逍遥丸(JWXYP)改善抑郁样行为的功效物质及作用机制。方法通过TCMSP、TCMIP等数据库,筛选加味逍遥丸治疗抑郁症的功效物质群、关键靶点及通路。将SD大鼠随机分为空白(Control)组、模型(CUMS)组、阳性组(1.8 mg/kg)组和加味逍遥丸低、中、高(JWXYP,1.44、2.88、4.32 g·kg^(-1)·d^(-1))组(n=6)。通过行为学实验评估大鼠抑郁样行为,HE染色观察肝脏和海马病理变化,ELISA检测血清和脑组织生化指标。血清代谢组学采用OPLS-DA方法筛选差异代谢物并进行通路分析。盲肠内容物进行16srDNA基因测序分析肠道菌群变化。结果网络药理学研究发现,加味逍遥丸中的薄荷酮和丹皮酚等关键成分可通过血脑屏障,调节炎症通路保护神经系统。动物实验显示,加味逍遥丸均显著改善模型大鼠的体质量、糖水偏好率及旷场中央区域活动时间(P<0.05);明显减少肝脏炎性细胞浸润和细胞坏死,改善海马神经元结构;降低血清中肿瘤坏死因子-α、白细胞介素-1β、白细胞介素-6水平以及脂多糖结合蛋白,上调外周血和大脑中5-羟色胺、血管活性肠肽的浓度(P<0.05),其中高剂量效果最为显著(P<0.01)。代谢组学分析显示,加味逍遥丸干预的差异代谢物包括吲哚-3-乙酰胺、乙酰左旋肉碱、3-甲基-L-组氨酸等,涉及次级胆汁酸生物合成、精氨酸和脯氨酸代谢和D-氨基酸代谢等多条通路(P<0.05)。16srDNA分析发现,加味逍遥丸组的Chao1、Observed和Shannon指数均明显升高,肠道菌群丰富度和均匀度增加,且菌鼠乳杆菌、肠乳酸杆菌的丰度显著提高。结论加味逍遥丸通过调节神经递质、抗炎抗氧化以及肠道菌群三条途径相互作用,改善情绪和认知功能减轻抑郁样症状。Objective To explore the bioactive components in Jiawei Xiaoyao Pills(JWXYP)and their mechanisms for alleviating depression-like behaviors.Methods The active compounds,key targets,and pathways of JWXYP were identified using TCMSP and TCMIP databases.Thirty-six SD rats were randomized equally into 6 groups including a control group and 5 chronic unpredictable mild stress(CUMS)-induced depression groups.After modeling,the 5 model groups were treated with daily gavage of normal saline,1.8 mg/kg fluoxetine hydrochloride(positive control drug),or JWXYP at 1.44,2.88,and 4.32 g/kg.The depression-like behaviors of the rats were evaluated using behavioral tests,and pathological changes in the liver and hippocampus were examined with HE staining.The biochemical indicators in the serum and brain tissues were detected using ELISA.Serum metabolomics analysis was performed to identify the differential metabolites using OPLS-DA,and gut microbiota changes were analyzed using 16S rDNA sequencing.Results Network pharmacology revealed that menthone and paeonol in JWXYP were capable of penetrating the blood-brain barrier to regulate inflammatory pathways and protect the nervous system.In the rat models subjected to CUMS,treatment with JWXYP significantly improved body weight loss,sucrose preference and open field activities,reduced liver inflammation,alleviated structural changes in the hippocampal neurons,decreased serum levels of TNF-α,IL-1β,IL-6 and LBP,and increased 5-HT and VIP concentrations in the serum and brain tissue,and these effects were the most pronounced in the high-dose group.Metabolomics analysis showed changes in such metabolites as indole-3-acetamide and acetyl-L-carnitine in JWXYP-treated rats,involving the pathways for bile acid biosynthesis and amino acid metabolism.16S rDNA analysis demonstrated increased gut microbiota diversity and increased abundance of Lactobacillus species in JWXYP-treated rats.Conclusion JWXYP alleviates depression-like symptoms in rats by regulating the neurotransmitters,inhibiting in

关 键 词：加味逍遥丸 网络药理学 肠道菌群 血清代谢组 抑郁样行为 

分 类 号：R27[医药卫生—中医学]