1.中国中医科学院 中药研究所,国家药品监督管理局 中医药研究与评价重点实验室,北京 100700
2.辽宁上药好护士药业(集团)有限公司,辽宁 本溪 117000
李珊珊,在读硕士,从事中药整合药理学研究,E-mail:1967768717@qq.com
王萍,博士,研究员,从事中药整合药理学研究,E-mail:hudielanwp@sina.com
收稿:2024-11-11,
录用:2025-02-07,
网络出版:2025-02-07,
纸质出版:2025-04-20
移动端阅览
李珊珊,钟余特,向小梅等.经典名方人参五味子汤治疗脾肺气虚证的药效物质基础和作用机制分析[J].中国实验方剂学杂志,2025,31(08):31-39.
LI Shanshan,ZHONG Yute,XIANG Xiaomei,et al.Analysis on Pharmacodynamic Material Basis and Mechanism of Famous Classical Formula Renshen Wuweizi Tang in Treatment of Spleen and Lung Qi Deficiency Syndrome[J].Chinese Journal of Experimental Traditional Medical Formulae,2025,31(08):31-39.
李珊珊,钟余特,向小梅等.经典名方人参五味子汤治疗脾肺气虚证的药效物质基础和作用机制分析[J].中国实验方剂学杂志,2025,31(08):31-39. DOI: 10.13422/j.cnki.syfjx.20251361.
LI Shanshan,ZHONG Yute,XIANG Xiaomei,et al.Analysis on Pharmacodynamic Material Basis and Mechanism of Famous Classical Formula Renshen Wuweizi Tang in Treatment of Spleen and Lung Qi Deficiency Syndrome[J].Chinese Journal of Experimental Traditional Medical Formulae,2025,31(08):31-39. DOI: 10.13422/j.cnki.syfjx.20251361.
目的
2
基于超高效液相色谱-四极杆-飞行时间串联质谱法(UPLC-Q-TOF-MS/MS)、网络药理学及分子对接技术,挖掘经典名方人参五味子汤治疗脾肺气虚证的药效物质基础和作用机制。
方法
2
采用UPLC-Q-TOF-MS/MS系统表征与鉴定人参五味子汤水煎液中的化学成分。运用网络药理学方法进行潜在活性成分筛选,收集成分靶标与脾肺气虚证相关证候基因集,通过STRING数据库获取蛋白质相互作用关系。使用Cytoscape 3.9.1构建“方-证”关联网络并计算拓扑特征值,对核心基因进行基因本体(GO)功能及京都基因与基因组百科全书(KEGG)通路富集分析以探索潜在药效环节,计算方药靶标网络到药效环节基因网络之间的平均最短路径以发现优势药效环节,使用MCODE插件从优势药效环节中辨识出核心基因簇,通过基因表达综合数据库(GEO)对其进行验证,并对关键成分与核心靶点进行分子对接。
结果
2
在负离子模式下鉴定了137个成分,正离子模式下鉴定了80个成分,去重后共有185个成分,主要由三萜皂苷类(49个)和黄酮类(54个)化合物组成。基于“方-证”关联网络分析,确定“能量代谢”是人参五味子汤治疗脾肺气虚证的优势药效环节;分子对接结果显示,源于该方剂中人参、白术、甘草、茯苓4味药材的腺苷、白术内酯Ⅱ、白术内酯Ⅲ、人参皂苷Rg
1
、甘草皂苷B
2
、甘草皂苷E
2
、菜油甾醇7个成分可能通过作用于肿瘤坏死因子(TNF)、甘油醛-3-磷酸脱氢酶(GAPDH)、环磷腺苷效应元件结合蛋白1(CREB1)、白细胞介素(IL)-6、过氧化物酶体增殖物激活受体
α
(PPAR
α
)、核转录因子-
κ
B1(NF-
κ
B1)6个靶标发挥对能量代谢的调控作用,从而改善脾肺气虚证相关疾病症状。
结论
2
该研究建立了快速表征和鉴定人参五味子汤水煎液中化学成分的液质联用分析方法,拓展了对该方的物质组成的认识,并发现7个成分可能通过6个靶标作用于关键优势药效环节“能量代谢”,以改善脾肺气虚证的相关症状,可为经典名方人参五味子汤后续物质基准及作用机制探索提供参考。
Objective
2
Based on ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS), network pharmacology and molecular docking techniques, to explore the pharmacodynamic material basis and mechanism of Renshen Wuweizi Tang in treating spleen-lung Qi deficiency syndrome.
Methods
2
The chemical components in the decoction of Renshen Wuweizi Tang were systematically characterized and identified by UPLC-Q-TOF-MS/MS, and network pharmacology was used to screen potential active ingredients, collect component targets and gene sets related to spleen-lung Qi deficiency syndrome, and obtain protein interaction relationships through STRING. Cytoscape 3.9.1 was used to construct a "formula-syndrome" association network and calculate topological feature values. Gene ontology(GO) function and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed on core genes to explore potential pharmacodynamic links, the average shortest path between the formula-drug target network and the pharmacodynamic link gene network was calculated to discover dominant pharmacodynamic links, and MCODE plugin was used to identify core gene clusters from the dominant pharmacodynamic links, which were validated using Gene Expression Omnibus(GEO), and molecular docking was performed between key components and core targets.
Results
2
One hundred and thirty-seven components were identified in the negative ion mode, and eighty components were identified in the positive ion mode. After deduplication, a total of 185 components were identified, mainly composed of triterpenoid saponins(49) and flavonoids(54). Based on the "formula-syndrome" correlation network analysis, energy metabolism was determined to be the dominant pharmacodynamic link of Renshen Wuweizi Tang in the treatment of spleen-lung Qi deficiency syndrome. The results of molecular docking showed that 7 components(adenosine, atractylenolide Ⅱ, atractylenolide Ⅲ, ginsenoside Rg
1
, glycyrrhizin B
2
, glycyrrhizin E
2
and campesterol) from 4 medicinal materials(Ginseng Radix et Rhizoma, Atractylodis Macrocephalae Rhizoma, Glycyrrhizae Radix et Rhizoma and Poria) in this formula might regulate energy metabolism by acting on 6 targets, namely cyclic adenosine monophosphate-response element binding protein 1(CREB1), glyceraldehyde-3-phosphate dehydrogenase(GAPDH), interleukin(IL)-6, nuclear transcription factor(NF)-
κ
B1, peroxisome proliferator-activated receptor
α
(PPAR
α
), and tumor necrosis factor(TNF), thus improving the symptoms of diseases related to spleen-lung Qi deficiency syndrome.
Conclusion
2
This study established a UPLC-Q-TOF-MS/MS for rapid characterization and identification of chemical components in the decoction of Renshen Wuweizi Tang, expanding the understanding of the material composition of this formula, and found that 7 components might act on the key advantageous pharmacodynamic link "energy metabolism" through 6 targets to improve the related symptoms of spleen-lung Qi deficiency syndrome. This can provide a reference for the subsequent exploration of the material benchmark and mechanism of the famous classical formula.
舒秀锦 , 许庆龄 , 江宙蔚 , 等 . 人参五味子汤加减联合调肺运脾小儿推拿法对儿童咳嗽肺脾气虚证的应用效果 [J]. 中华养生保健 , 2024 , 42 ( 15 ): 26 - 29 .
SHU X J , XU Q L , JIANG Z W , et al . Application effect of modified ginseng schisandra decoction combined with infantile massage method of regulating lung and activating spleen on children's cough with lung and spleen Qi deficiency syndrome [J]. Chin Health Care , 2024 , 42 ( 15 ): 26 - 29 .
穆开朗 , 陈嘉悦 , 锦王 , 等 . 人参五味子汤治疗小儿哮喘的网络药理学研究及分子对接验证 [J]. 自然科学 , 2022 , 10 ( 6 ): 10 .
MU K L , CHEN J Y , JIN W , et al . Network pharmacology study and molecular docking verification of ginseng and schisandra decoction in the treatment of pediatric asthma [J]. Nat Sci , 2022 , 10 ( 6 ): 10 .
祝海波 , 周苗苗 , 杨顼 , 等 . 中医调治方案在儿童肺炎恢复期(肺脾气虚证、阴虚肺热症)中的疗效研究 [J]. 辽宁中医杂志 , 2020 , 47 ( 10 ): 86 - 89 .
ZHU H B , ZHOU M M , YANG Q , et al . Therapeutic effects of TCM regulation regimen in recovery period of pneumonia in children(lung-spleen Qi deficiency syndrome,Yin deficiency and lung heat syndrome) [J]. Liaoning J Tradit Chin Med , 2020 , 47 ( 10 ): 86 - 89 .
易延逵 , 邓虹珠 , 董常荣 , 等 . 参芪花粉制剂组方对脾肺气虚症的运用探讨 [J]. 内蒙古中医药 , 2014 , 33 ( 1 ): 116 - 118 .
YI Y K , DENG H Z , DONG C G , et al . Probe on the applying of the prescription of Shenqihuafen preparation to pifeiqixv disease [J]. Inner Mongolia J Tradit Chin Med , 2014 , 33 ( 1 ): 116 - 118 .
白焕强 , 王淑萍 . 益肺化痰汤加减治疗脾肺气虚证喘证疗效观察 [J]. 中国中医急症 , 2018 , 27 ( 8 ): 1451 - 1453 .
BAI H Q , WANG S P . Observation on the therapeutic effect of modified Yifei Huatan Tang on spleen lung Qi deficiency and asthma syndrome [J]. J Emerg Tradit Chin Med , 2018 , 27 ( 8 ): 1451 - 1453 .
王芳 , 李春英 , 易艳 , 等 . 马兜铃水提物在大鼠体内代谢产物的定性分析 [J]. 中国实验方剂学杂志 , 2023 , 29 ( 13 ): 112 - 121 .
WANG F , LI C Y , YI Y , et al . Qualitative analysis of metabolites of Aristolochiae Fructus aqueous extract in rats [J]. Chin J Exp Tradit Med Form , 2023 , 29 ( 13 ): 112 - 121 .
卡地尔亚·库尔班 , 王长虹 , 徐楠 , 等 . 去氢骆驼蓬碱在大鼠体内代谢产物与代谢途径的UPLC-Q-TOF-MS分析 [J]. 中国实验方剂学杂志 , 2024 , 30 ( 11 ): 202 - 209 .
CARTIERA K , WANG C H , XU N , et al . Analysis on metabolites and metabolic pathways of harmine in rats by UPLC-Q-TOF-MS [J]. Chin J Exp Tradit Med Form , 2024 , 30 ( 11 ): 202 - 209 .
JIANG H , CHEN J , LI X , et al . Systematic identification of chemical components in Fufang Shuanghua oral liquid and screening of potential active components against SARS-CoV-2 protease [J]. J Pharm Biomed Anal , 2023 , 223 : 115118 .
高文晶 , 李珊珊 , 向小梅 , 等 . 基于UPLC-Q-TOF-MS/MS分析经典名方保元汤的物质基础 [J]. 中国实验方剂学杂志 , 2024 , 30 ( 22 ): 243 - 248 .
GAO W J , LI S S , XIANG X M , et al . Analysis of material basis of famous classical formula Baoyuantang based on UPLC-Q-TOF-MS/MS [J]. Chin J Exp Tradit Med Form , 2024 , 30 ( 22 ): 243 - 248 .
魏朝法 , 朱利婉 , 兰晓燕 , 等 . 基于UPLC-Q-TOF-MS结合UNIFI及数据库快速表征鉴定广藿香中非挥发性成分 [J]. 中国中药杂志 , 2023 , 48 ( 14 ): 3826 - 3838 .
WEI C F , ZHU L W , LAN X Y , et al . Rapid characterization and identification of non-volatile constituents in Pogostemonis Herba by UPLC-Q-TOF-MS combined with UNIFI and an in-house library [J]. Chin J Chin Mater Med , 2023 , 48 ( 14 ): 3826 - 3838 .
CHANG H , LV S J , YUAN T T , et al . Identification and analysis of chemical constituents and rat serum metabolites in Gushuling using UPLC-Q-TOF/MS coupled with novel informatics UNIFI platform [J]. Evid Based Complement Alternat Med , 2021 , 2021 : 2894306 .
ZHANG Y Q , LI X , SHI Y L , et al . ETCM v2.0:An update with comprehensive resource and rich annotations for traditional Chinese medicine [J]. Acta Pharm Sin B , 2023 , 13 ( 6 ): 2559 - 2571 .
ZHANG Y Q , WANG N , DU X , et al . SoFDA:An integrated web platform from syndrome ontology to network-based evaluation of disease-syndrome-formula associations for precision medicine [J]. Sci Bull(Beijing) , 2022 , 67 ( 11 ): 1097 - 1101 .
何天雨 , 王璐 , 李林 , 等 . 基于UPLC-Q-TOF-MS/MS技术的经典名方竹茹汤化学成分鉴定及网络药理学研究 [J]. 中国中药杂志 , 2022 , 47 ( 19 ): 5235 - 5245 .
HE T Y , WANG L , LI L , et al . Identification of chemical components based on UPLC-Q-TOF-MS/MS and network pharmacology of Zhuru decoction [J]. Chin J Chin Mater Med , 2022 , 47 ( 19 ): 5235 - 5245 .
许如玲 , 范君婷 , 董惠敏 , 等 . 经典名方黄芪桂枝五物汤标准煎液化学成分的UPLC-Q-TOF-MS分析 [J]. 中国中药杂志 , 2020 , 45 ( 23 ): 5614 - 5630 .
XU R L , FAN J T , DONG H M , et al . UPLC-Q-TOF-MS analysis on chemical constituents of classical prescription Huangqi Guizhi Wuwu Tang standard decoction [J]. Chin J Chin Mater Med , 2020 , 45 ( 23 ): 5614 - 5630 .
李雷 , 张艳丽 , 陈美庆 , 等 . UPLC-Q-TOF-MS/MS技术分析参苓白术散化学成分及入血成分 [J]. 中药新药与临床药理 , 2024 , 35 ( 4 ): 553 - 562 .
LI L , ZHANG Y L , CHEN Q M , et al . Analysis on chemical composition and constituents absorbed in the blood of Shenling Baizhu San by UPLC-Q-TOF-MS/MS [J]. Tradit Chin Drug Res Pharmacol , 2024 , 35 ( 4 ): 553 - 562 .
王静 , 姚长良 , 张建青 , 等 . 基于UPLC-Q-TOF-MS的人参配方颗粒化学成分及指纹图谱研究 [J]. 中草药 , 2022 , 53 ( 11 ): 3286 - 3294 .
WANG J , YAO C L , ZHANG J Q , et al . Study on chemical components and chromatographic fingerprints of Ginseng dispensing granules based on UPLC-Q-TOF-MS [J]. Chin Tradit Herbal Drugs , 2022 , 53 ( 11 ): 3286 - 3294 .
CHEN L H , ZHANG Y B , YANG X W , et al . Characterization and quantification of ginsenosides from the root of Panax quinquefolius L. by integrating untargeted metabolites and targeted analysis using UPLC-Triple TOF-MS coupled with UFLC-ESI-MS/MS [J]. Food Chem , 2022 , 384 : 132466 .
JIANG H L , SOLYOM A M , TIMMERMANN B N , et al . Characterization of gingerol‐related compounds in ginger rhizome ( Zingiber officinale Rosc.) by high‐performance liquid chromatography/electrospray ionization mass spectrometry [J]. Rapid Commun Mass Spectrom , 2005 , 19 ( 20 ): 2957 - 2964 .
LI S L , LAI S F , SONG J Z , et al . Decocting-induced chemical transformations and global quality of DuShen-Tang,the decoction of ginseng evaluated by UPLC-Q-TOF-MS/MS based chemical profiling approach [J]. J Pharm Biomed Anal , 2010 , 53 ( 4 ): 946 - 957 .
YIN Q W , WANG P , ZHANG A H , et al . Ultra-performance LC-ESI/quadrupole-TOF MS for rapid analysis of chemical constituents of Shaoyao-Gancao decoction [J]. J Sep Sci , 2013 , 36 ( 7 ): 1238 - 1246 .
HUANG X , LIU Y , ZHANG N , et al . UPLC Orbitrap HRMS analysis of Panax quinquefolium L. for authentication of Panax genus with chemometric Methods [J]. J Chromatogr Sci , 2018 , 56 ( 1 ): 25 - 35 .
QIN Y , ZHANG Z , JIANG R . Ginsenoside Rg 1 promotes wound healing in mice with superficial second-degree burns through energy metabolism,cell migration,and cell adhesion pathways [J]. J Med Food , 2025 , 28 ( 2 ): 165 - 173 .
DAI X , LIU Y , LIU T , et al . SiJunZi decoction ameliorates bone quality and redox homeostasis and regulates advanced glycation end products/receptor for advanced glycation end products and WNT/ β -catenin signaling pathways in diabetic mice [J]. J Ethnopharmacol , 2024 , 319 ( Pt 2 ): 117167 .
ZHANG W , MENG Z , YU P , et al . Metabolomics-based analysis of nitric oxide regulation of ginseng herb quality [J]. J Sci Food Agric , 2024 . doi: 10.1002/jsfa.14062 http://dx.doi.org/10.1002/jsfa.14062 .
ZHAO C Z , DING H M , HU Z Q , et al . Exploring the mechanism of Ling-Gui-Zhu-Gan decoction in metabolic cardiomyopathy via inhibiting ferroptosis [J]. Phytomedicine , 2024 , 135 : 156234 .
TIAN S , REN L , LIU C , et al . Atractylenolide Ⅱ suppresses glycolysis and induces apoptosis by blocking the PADI3-ERK signaling pathway in endometrial cancer cells [J]. Molecules , 2024 , 29 ( 5 ): 939 .
YEGUTKIN G G , BOISON D . ATP and adenosine metabolism in cancer:Exploitation for therapeutic gain [J]. Pharmacol Rev , 2022 , 74 ( 3 ): 797 - 822
HOXHAJ G , MANNING BD . The PI3K-Akt network at the interface of oncogenic signalling and cancer metabolism [J]. Nat Rev Cancer , 2020 , 20 ( 2 ): 74 - 88 .
OLEJNIK A , RADAJEWSKA A , KRZYWONOS-ZAWADZKA A , et al . Klotho inhibits IGF1R/PI3K/Akt signalling pathway and protects the heart from oxidative stress during ischemia/reperfusion injury [J]. Sci Rep , 2023 , 13 ( 1 ): 20312 .
库来娟 . 中西医结合治疗小儿支气管哮喘脾肺气虚证临床观察 [J]. 实用中医药杂志 , 2020 , 36 ( 2 ): 177 - 178 .
KU L J . Clinical Observation of integrated traditional Chinese and western medicine in the treatment of spleen and lung Qi deficiency syndrome in children with bronchial asthma [J]. J Practical Tradit Chin Med , 2020 , 36 ( 2 ): 177 - 178 .
魏娟 , 苏冠凤 , 王春兰 , 等 . 一理三法治疗小儿过敏性咳嗽(脾肺气虚证)临床研究 [J]. 光明中医 , 2024 , 39 ( 14 ): 2876 - 2879 .
WEI J , SU G F , WANG C L , et al . Clinical study on the treatment of pediatric allergic cough(spleen lung Qi deficiency syndrome) with one principle and three methods [J]. Guangming J Chin Med , 2024 , 39 ( 14 ): 2876 - 2879 .
舒秀锦 , 许庆龄 , 江宙蔚 , 等 . 人参五味子汤加减联合调肺运脾小儿推拿法对儿童咳嗽肺脾气虚证的应用效果 [J]. 中华养生保健 , 2024 , 42 ( 15 ): 26 - 29 .
SHU X J , XU Q L , JIANG Z W , et al . Application effect of modified ginseng schisandra decoction combined with infantile massage method of regulating lung and activating spleen on children's cough with lung and spleen Qi deficiency syndrome [J]. Chin Health Care , 2024 , 42 ( 15 ): 26 - 29 .
于洋 , 辛杨 , 王海军 , 等 . 基于细胞实验及网络药理学探究人参五味子汤对肺炎的治疗作用 [J]. 齐齐哈尔大学学报:自然科学版 , 2024 , 40 ( 5 ): 63 - 68 .
YU Y , XIN Y , WANG H J , et al . Exploring the therapeutic effect of Renshen Wuweizi decoction on pneumonia based on cell experiment and network pharmacology [J]. J Qiqihar Univ:Nat Sci Ed , 2024 , 40 ( 5 ): 63 - 68 .
袁中杰 , 肖悦 , 刘真 , 等 . 基于线粒体生物发生探讨人参总次苷对缺氧下H9c2细胞凋亡和能量代谢的影响 [J]. 中国中药杂志 , 2025 , doi: 10.19540/j.cnki.cjcmm.20240919.405 http://dx.doi.org/10.19540/j.cnki.cjcmm.20240919.405 .
YUAN Z J , XIAO Y , LIU Z , et al . Effect of total secondary ginsenosides on apoptosis and energy metabolism of H9c2 cells under hypoxia based on mitochondrial biogenesis [J]. China J Chin Mater Med , 2025 , doi: 10.19540/j.cnki.cjcmm.20240919.405 http://dx.doi.org/10.19540/j.cnki.cjcmm.20240919.405
PAN M , DENG Y , QIU Y , et al . Shenling Baizhu powder alleviates non-alcoholic fatty liver disease by modulating autophagy and energy metabolism in high-fat diet-induced rats [J]. Phytomedicine , 2024 , 130 : 155712 .
CHENXING W , JIE S , YAJUAN T , et al . The rhizomes of Atractylodes macrocephala Koidz improve gastrointestinal health and pregnancy outcomes in pregnant mice via modulating intestinal barrier and water-fluid metabolism [J]. J Ethnopharmacol , 2024 , 326 : 117971 .
ZENG L Y , SUN S D , CHEN P W , et al . Mechanism of Peitu Shengjin formula Shenlingbaizhu powder in treating bronchial asthma and allergic colitis through different diseases with simultaneous treatment based on network pharmacology and molecular docking [J]. Evid Based Complement Alternat Med , 2022 , 2022 : 4687788 .
YU W , WANG G L , LU C , et al . Pharmacological mechanism of Shenlingbaizhu formula against experimental colitis [J]. Phytomedicine , 2022 , 98 : 153961 .
0
浏览量
212
下载量
0
CSCD
关联资源
相关文章
相关作者
相关机构
京公网安备11010802024621
