摘要
目的:探究獐牙菜(Swertia bimaculata(Siebold&Zucc.)Hook.f.et Thomson ex C.B.Clarke,SBH)水提物对神经细胞的保护作用及潜在分子作用机制,旨在为獐牙菜的开发与利用提供理论依据。方法:采用网络药理学预测SBH缓解焦虑障碍(Anxiety Disorder)潜在分子机制。以谷氨酸诱导小鼠海马神经元细胞(HT-22)建立体外细胞损伤模型,使用MTT法及RTCA(Real-time cell analyzer)法检测细胞活力。试剂盒检测细胞内SOD、MDA及CORT水平,实时荧光定量(qRT-PCR)法测定核心通路相关基因及BDNF、PSD95和SYP mNRA的表达。并通过SPSSPRO平台,对SBH、SD及SM神经保护作用进行综合评价。结果:通过检索共筛选得到共同靶点311个,其中多数核心靶点富集于PI3K/AKT信号通路上。MTT实验表明,高浓度谷氨酸干预可显著损伤HT-22细胞,下调PI3KR1、mTOR、BDNF、PSD95及SYP mRNA水平,以及氧化应激指标SOD水平;上调MDA、CORT水平。SBH、SD及SM均可不同程度逆转上述指标。熵权TOPSIS法综合评价表明:同剂量下,SD药效水平较优于SM。结论:獐牙菜及其活性单体獐牙菜苷及獐牙菜苦苷可通过调节PI3K/AKT信号通路,改善细胞突触可塑性共同发挥保护HT-22细胞,进而发挥缓解焦虑障碍作用。
Objective:To investigate the effects and potential molecular mechanisms of water extracts of Swertia bimaculata(Siebold&Zucc.)Hook.f.&Thomson ex C.B.Clarke(SBH)on nervous system cells by constructing HT-22,cell neuroinflammatory models in vitro,to provide the theoretical basis for utilizing Swertia bimaculata(Siebold&Zucc.)Hook.f.et Thomson ex C.B.Clarke(SBH)and allow full play to the value and advantages of Chinese medicine.Methods:Network pharmacology was used to predict the potential molecular mechanism of SBH in relieving anxiety disorder.Hippocampal neurons(HT-22)were injured by glutamate in vitro.Cell viability was detected by MTT assay and RTCA(real-time cell analyzer)assay.The kit detected the levels of SOD,MDA and CORT,and the mNRA expression of core pathway related genes and BDNF,PSD95 and SYP were detected by real-time fluorescence quantitative analysis(qRT-PCR).The entropy weight TOPSIS method was used to comprehensively evaluate the neuroprotective effects of SBH,SD and SM.Results:Most of the core targets were enriched in the PI3K/AKT signaling pathway.MTT assay showed that high-dose Glutamate could significantly damage HT-22 cells;down-regulate the mRNA levels of PI3KR1、mTOR、BDNF、PSD95,SYP and oxidative stress index SOD;up-regulate the level of MDA and CORT.SBH、SD,and SM can reverse the index accordingly.SBH、SD and SM can improve synaptic plasticity by promoting the expression of BDNF、PSD95、SYP;Regulate SOD and MDA to alleviate oxidative stress and act on PI3K/AKT pathway to protect HT-22 cells.Comprehensive evaluation by the entropy weight TOPSIS method showed that the efficacy level of SD was better than that of SM at the same dose.Conclusion:Swertia bimaculata(Siebold&Zucc.)Hook.f.et Thomson ex C.B.Clarke(SBH)and its active compound sweroside and swertiamarine can protect HT-22 cells by regulating PI3K/AKT signaling pathway and improving synaptic plasticity,thereby alleviating anxiety disorders.
作者
龙熠
盛望龙
李竣
陶浩
何志勇
黄先菊
Long Yi;Sheng Wanglong;Li Jun;Tao Hao;He Zhiyong;Huang Xianju(College of Pharmaceutical,South-Central University for Nationalities,Wuhan 430074,China;Experimental Teaching and Lab Management Center,South-Central University for Nationalities,Wuhan 430074,China)
出处
《亚太传统医药》
2025年第7期18-26,共9页
Asia-Pacific Traditional Medicine
基金
中南民族大学学术创新团队经费项目(XTZ24025)
湖北省科技创新基地(平台)计划(2024CFC003、2022EHB053)。
关键词
獐牙菜
神经细胞
焦虑障碍
神经炎症
Swertia Bimaculata(Siebold&Zucc.)Hook.f.et Thomson ex C.B.Clarke(SBH)
Nervous System Cells
Anxiety Disorder
Neuroinflammation
