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Article(id=1200860509521170546, tenantId=1146029695717560320, journalId=1189982191388893191, issueId=1200860506031518620, articleNumber=null, orderNo=null, doi=10.16438/j.0513-4870.2023-1184, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1697644800000, receivedDateStr=2023-10-19, revisedDate=1703692800000, revisedDateStr=2023-12-28, acceptedDate=null, acceptedDateStr=null, onlineDate=1764237056379, onlineDateStr=2025-11-27, pubDate=1715443200000, pubDateStr=2024-05-12, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1764237056379, onlineIssueDateStr=2025-11-27, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1764237056379, creator=13701087609, updateTime=1764237056379, updator=13701087609, issue=Issue{id=1200860506031518620, tenantId=1146029695717560320, journalId=1189982191388893191, year='2024', volume='59', issue='5', pageStart='1101', pageEnd='1508', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1764237055547, creator=13701087609, updateTime=1764241222263, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1200877982563824311, tenantId=1146029695717560320, journalId=1189982191388893191, issueId=1200860506031518620, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1200877982563824312, tenantId=1146029695717560320, journalId=1189982191388893191, issueId=1200860506031518620, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=1364, endPage=1373, ext={EN=ArticleExt(id=1200860511270195362, articleId=1200860509521170546, tenantId=1146029695717560320, journalId=1189982191388893191, language=EN, title=Spectrum-effect relationship combined with bioactivity evaluation to discover the main antidepressant active components of Baihe Dihuang decoction, columnId=1190335348761793317, journalTitle=Acta Pharmaceutica Sinica, columnName=Original Articles, runingTitle=null, highlight=null, articleAbstract=

The study utilized spectral correlation analyses combined with bioactivity evaluation to examine the effective components of antidepressants in the Baihe Dihuang decoction. Firstly, the chemical fingerprints for different extraction parts in the Baihe Dihuang decoction were achieved using HPLC and UHPLC-MS technology. Then, in order to evaluate the antidepressant effect of Baihe Dihuang decoction, the animal experimental protocol has been reviewed and approved by Laboratory Animal Ethics Committee of Hunan University of Chinese Medicine (No. LLBH-202104270001), in compliance with the Institutional Animal Care Guidelines. We recorded the distance of autonomous movement of mice in open field experiment, the immobility time of tail suspension test, and the forced swimming. Additionally, we measured the content of neurotransmitters. Finally, Pearson analysis, grey correlation analysis, and orthogonal partial least squares regression analysis were utilized to establish the correlation between antidepressant efficacy indicators and fingerprinting. The spectrum-effect relationship results were confirmed through the in vitro activity verification. This study demonstrated that regaloside A, B, C, catalpol, and Isoacteoside might be the main antidepressant components in Baihe Dihuang decoction. Furthermore, it was found that using diverse mathematical models and bioactivity evaluation could enhance the accuracy of the spectral correlation analyses results.

, correspAuthors=Lin TANG, authorNote=null, correspAuthorsNote=null, copyrightStatement=Copyright ©2024 Acta Pharmaceutica Sinica. All rights reserved., copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, authorCompany=null, fund=null, authors=null, authorsList=Chao HU, Hong-qing ZHAO, Jian LIU, Lu WANG, Lei YANG, Shui-han ZHANG, Lin TANG), CN=ArticleExt(id=1200860512364908773, articleId=1200860509521170546, tenantId=1146029695717560320, journalId=1189982191388893191, language=CN, title=基于谱效关系及活性验证的百合地黄汤抗抑郁成分研究, columnId=1190335348896011050, journalTitle=药学学报, columnName=研究论文, runingTitle=null, highlight=null, articleAbstract=

本研究通过谱效相关分析及活性验证探明百合地黄汤抗抑郁的药效成分。利用不同溶剂分次提取并结合HPLC和UHPLC-MS分析方法对百合地黄汤不同提取部位化学成分进行全面表征。动物实验方案经湖南中医药大学动物伦理委员会审查通过(审查号为LLBH-202104270001), 所有程序均严格按照动物使用和护理的伦理原则进行。采用旷场实验、悬尾实验、强迫游泳实验等经典行为学方法结合神经递质测定进行抗抑郁药效综合评价。整合三种相关分析方法进行谱效关联表征, 以三种关联分析所得药效成分的交集为潜在药效成分, 并进行了体外细胞实验验证。研究发现, 王百合苷A、B、C、梓醇和异毛蕊花糖苷可能是百合地黄汤发挥抗抑郁作用的主要药效物质, 同时也提示, 多元化的谱效相关分析及活性验证有助于提升谱效相关分析结果的准确性。

, correspAuthors=唐林, authorNote=null, correspAuthorsNote=
*唐林, Tel: 86-731-85600544, E-mail:
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Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression [J]. Nat Genet, 2018, 50: 668-681., articleTitle=null, refAbstract=null), Reference(id=1201106669695623944, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1200860509521170546, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[2], rfOrder=1, authorNames=null, journalName=null, refType=null, unstructuredReference=Buckner JD, Abarno CN, Lewis EM, et al. Increases in distress during stay-at-home mandates during the COVID-19 Pandemic: a longitudinal study [J]. Psychiatry Res, 2021, 298: 113821., articleTitle=null, refAbstract=null), Reference(id=1201106669813064465, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1200860509521170546, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[3], rfOrder=2, authorNames=null, journalName=null, refType=null, unstructuredReference=Zhao YT, Zhang ZL, Li XJ, et al. Research progress of classic prescription Baihe Dihuang decoction [J]. J Guangdong Pharm Univ (广东药科大学学报), 2022, 38: 137-142., articleTitle=null, refAbstract=null), Reference(id=1201106669955670811, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1200860509521170546, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[4], rfOrder=3, authorNames=null, journalName=null, refType=null, unstructuredReference=Li S, Wang ZY, Chang HJ, et al. Establishment of HPLC fingerprint and effects of antioxidant and radioresistance related to its spectrum study of Aucklandiae Radix [J]. Chin Tradit Herb Drugs (中草药), 2023, 54: 2580-2587., articleTitle=null, refAbstract=null), Reference(id=1201106670190551845, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1200860509521170546, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[5], rfOrder=4, authorNames=null, journalName=null, refType=null, unstructuredReference=Liu X, Yu H, Song JT, et al. Integration of plasma metabolomics and spectrum-effect correlation for profiling the mechanism and pharmacodynamic substances on attenuating hepatic fibrosis of Bupleuri Radix and Paeoniae Radix Alba before and after vinegar-processing and compatibility [J]. Acta Pharm Sin (药学学报), 2023, 58: 1790-1801., articleTitle=null, refAbstract=null), Reference(id=1201106670328963881, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1200860509521170546, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[6], rfOrder=5, authorNames=null, journalName=null, refType=null, unstructuredReference=Jiang N, Zhang YW, Yao CH, et al. Overview of animal behavioral tests of depression [J]. Acta Lab Anim Sci Sin (中国实验动物学报), 2021, 29: 830-838., articleTitle=null, refAbstract=null), Reference(id=1201106670505124656, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1200860509521170546, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[7], rfOrder=6, authorNames=null, journalName=null, refType=null, unstructuredReference=Tang L, Zhao HQ, Yang H, et al. Optimization of extraction process of polysaccharide from Baihe dihuang decoction and study on its antianxiety and anti-depression efficacy [J]. China Pharm (中国药房), 2023, 34: 923-928., articleTitle=null, refAbstract=null), Reference(id=1201106670689674041, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1200860509521170546, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[8], rfOrder=7, authorNames=null, journalName=null, refType=null, unstructuredReference=Feng LM, Chen YY, Yue SJ, et al. Quantitative identification of TCM Q-markers based on analytical hierarchy and the entropy weight comprehensive method by taking Shaoyao Gancao decoction as an example [J]. Acta Pharm Sin (药学学报), 2021, 56: 296-305., articleTitle=null, refAbstract=null), Reference(id=1201106671889244990, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1200860509521170546, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[9], rfOrder=8, authorNames=null, journalName=null, refType=null, unstructuredReference=Tang L, Lu AJ, Wang L, et al. Optimization of the molding process of Zhiyangrunfu Cream [J]. Chin Tradit Pat Med (中成药), 2022, 44: 3614-3418., articleTitle=null, refAbstract=null), Reference(id=1201106672027657030, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1200860509521170546, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[10], rfOrder=9, authorNames=null, journalName=null, refType=null, unstructuredReference=Wu HW, Li DH, Zhang YG, et al. Comprehensive quality evaluation of Astragali Radix processed by different methods based on entropy weight TOPSIS model [J]. Chin Pharm J (中国药学杂志), 2021, 56: 1325-1331., articleTitle=null, refAbstract=null), Reference(id=1201106672174457680, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1200860509521170546, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[11], rfOrder=10, authorNames=null, journalName=null, refType=null, unstructuredReference=Liu J, Liu L, Tang L, et al. Protective effects and mechanism of Zuogui Jiangtang Jieyu Formulation on hippocampal neuron of NVU induced by autophagy in diabetes mellitus with depression [J]. Chin Tradit Herb Drugs (中草药), 2019, 50: 2420-2427., articleTitle=null, refAbstract=null), Reference(id=1201106672283509590, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1200860509521170546, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[12], rfOrder=11, authorNames=null, journalName=null, refType=null, unstructuredReference=Tian P, Zhang W, Li KY, et al. Effect of Rehmanniae Radix on depression-like behavior and hippocampal monoamine neurotransmitters of chronic unpredictable mild stress model rats [J]. China J Chin Mater Med (中国中药杂志), 2022, 47: 4691-4697., articleTitle=null, refAbstract=null), Reference(id=1201106672434504538, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1200860509521170546, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[13], rfOrder=12, authorNames=null, journalName=null, refType=null, unstructuredReference=Tao J, Zhou M, Wang YT, et al. The antidepressant effect of myricetin and its regulatory mechanism on neurotransmitters [J]. Chin Tradit Pat Med (中成药), 2021, 43: 3195-3198., articleTitle=null, refAbstract=null), Reference(id=1201106672598082403, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1200860509521170546, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[14], rfOrder=13, authorNames=null, journalName=null, refType=null, unstructuredReference=Wang ZY, Yang SY, Lv W, et al. Analysis of spectrum-activity relationship among antioxidant parts of Lycii Fructus using three different chemometrics methods [J]. China J Chin Mater Med (中国中药杂志), 2021, 46: 3377-3387., articleTitle=null, refAbstract=null), Reference(id=1201106672719717226, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1200860509521170546, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[15], rfOrder=14, authorNames=null, journalName=null, refType=null, unstructuredReference=Wang Y, Peng X, He YL, et al. Spectrum-effect relationship of anti-inflammatory active components from nonvolatile fraction of Blumea balsamifera based on gray correlation analysis [J]. Chin J Exp Tradit Med Form (中国实验方剂学杂志), 2019, 25: 180-186., articleTitle=null, refAbstract=null), Reference(id=1201106672832963441, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1200860509521170546, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[16], rfOrder=15, authorNames=null, journalName=null, refType=null, unstructuredReference=Lin MY, Zhang YP, Li Y, et al. Spectra-effect relationship of anti-inflammation of Salvia miltiorrhiza extract based on gray correlation analysis [J]. Chin Tradit Herb Drugs (中草药), 2017, 48: 3447-3452., articleTitle=null, refAbstract=null), Reference(id=1201106672958792568, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1200860509521170546, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[17], rfOrder=16, authorNames=null, journalName=null, refType=null, unstructuredReference=Peng LY, Liang Y, Shi JJ, et al. Relationship between HPLC fingerprint and total antioxidant activity of Danshen [J]. Pharmacol Clin Chin Mater Med (中药药理与临床), 2022, 38: 110-115., articleTitle=null, refAbstract=null), Reference(id=1201106673113981823, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1200860509521170546, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[18], rfOrder=17, authorNames=null, journalName=null, refType=null, unstructuredReference=Sun F, Wu XQ, Qi Y, et al. Application of partial least squares algorithm to explore bioactive components of crude and stir-baked hawthorn for invigorating spleen and promoting digestion [J]. China J Chin Mater Med (中国中药杂志), 2023, 48: 958-965., articleTitle=null, refAbstract=null), Reference(id=1201106673264976774, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1200860509521170546, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[19], rfOrder=18, authorNames=null, journalName=null, refType=null, unstructuredReference=Lee SH, Kim NS, Choi M, et al. LGI1 governs neuritin-mediated resilience to chronic stress [J]. Neurobiol Stress, 2021, 15: 100373., articleTitle=null, refAbstract=null), Reference(id=1201106673369834378, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1200860509521170546, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[20], rfOrder=19, authorNames=null, journalName=null, refType=null, unstructuredReference=Willard SL, Riddle DR, Forbes ME, et al. Cell number and neuropil alterations in subregions of the anterior hippocampus in a female monkey model of depression [J]. Biol Psychiatry, 2013, 74: 890-897., articleTitle=null, refAbstract=null), Reference(id=1201106673474691984, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1200860509521170546, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[21], rfOrder=20, authorNames=null, journalName=null, refType=null, unstructuredReference=Pacheco A, Aguayo FI, Aliaga E, et al. Chronic stress triggers expression of immediate early genes and differentially affects the expression of AMPA and NMDA Subunits in dorsal and ventral hippocampus of rats [J]. 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Hunan Academy of Chinese Medicine, Changsha 410208, China), AuthorCompanyExt(id=1201106654570963815, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1200860509521170546, companyId=1201106654529020765, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=3.湖南省中医药研究院, 湖南 长沙 410208)])], figs=[ArticleFig(id=1201106664054284720, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1200860509521170546, language=EN, label=null, caption=null, figureFileSmall=MpuzDTa2BMfAeP1PjhtbRg==, figureFileBig=i9pZHZaSHh1MGW6DX3lbPQ==, tableContent=null), ArticleFig(id=1201106664280777154, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1200860509521170546, language=CN, label=Figure 1, caption= HPLC chromatograms of mixed reference substances (A) and Baihe Dihuang decoction common pattern (B). 2: Catalpol; 6: Regaloside C; 20: Regaloside A; 21: Rehmaionoside A; 31: Acteoside; 33: Regaloside B; 34: Isoacteoside. The other peaks remain unknown , figureFileSmall=MpuzDTa2BMfAeP1PjhtbRg==, figureFileBig=i9pZHZaSHh1MGW6DX3lbPQ==, tableContent=null), ArticleFig(id=1201106664494686679, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1200860509521170546, language=EN, label=null, caption=null, figureFileSmall=dHc41WL3NpcAUIKq835I2w==, figureFileBig=hXObG6VdpkII86GH2Fuk8A==, tableContent=null), ArticleFig(id=1201106664628904418, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1200860509521170546, language=CN, label=Figure 2, caption= S1-S8 fractions of Baihe Dihuang decoction improved depression-like behaviors (A-C) and neurotransmitters (D, E). <i>n</i> = 6, <span class="mag-xml-inline-formula"><tex-math id="M2">$ \stackrel{-}{x} $</tex-math></span> ± <i>s</i>. <sup>#</sup><i>P</i> < 0.05, <sup>##</sup><i>P</i> < 0.01 <i>vs</i> CON. OFT: Open-field test; FST: Forced swim test; TST: Tail suspension test; 5-HT: 5-Hydroxytryptamine; NE: Norepinephrine; CON: Blank control group; VLF: Venlafaxine group; S1: 55% Ethanol fraction; S2: 75% Ethanol fraction; S3: 95% Ethanol fraction; S4: Water fraction; S5: Chloroform fraction; S6: Ethyl acetate fraction; S7: Butanol fraction; S8: Remaining water fraction , figureFileSmall=dHc41WL3NpcAUIKq835I2w==, figureFileBig=hXObG6VdpkII86GH2Fuk8A==, tableContent=null), ArticleFig(id=1201106664813453813, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1200860509521170546, language=EN, label=null, caption=null, figureFileSmall=CH8oWMQJrb7iqHOv/qKNbA==, figureFileBig=cyHFruEb+s7ITlAG4xpRcA==, tableContent=null), ArticleFig(id=1201106664960254463, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1200860509521170546, language=CN, label=Figure 3, caption= Active ingredients improved neuronal cell viability and morphology (A), apoptosis (B), synaptic damage (C), neurotransmitters (D) (<i>n</i> = 3, ELISA). MOD: Model group. <sup>**</sup><i>P</i> < 0.01 <i>vs</i> CON; <sup>#</sup><i>P</i> < 0.05, <sup>##</sup><i>P</i> < 0.01 <i>vs</i> MOD , figureFileSmall=CH8oWMQJrb7iqHOv/qKNbA==, figureFileBig=cyHFruEb+s7ITlAG4xpRcA==, tableContent=null), ArticleFig(id=1201106665148998155, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1200860509521170546, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
SampleD+D-CPrioritisation order
S10.2540.3170.5551
S20.3290.2450.4276
S30.3180.2160.4058
S40.2590.2450.4862
S50.3040.2120.4117
S60.2820.2310.4505
S70.2910.2720.4833
S80.2710.2250.4534
), ArticleFig(id=1201106665446793760, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1200860509521170546, language=CN, label=Table 1, caption=

The overall evaluation of antidepressant activity of S1-S8 fractions of Baihe Dihuang decoction by TOPSIS method. D+: Distance of positive ideal solution; D-: Distance of negative ideal solution; C: The degree of closeness of each alternative to the ideal solution

, figureFileSmall=null, figureFileBig=null, tableContent=
SampleD+D-CPrioritisation order
S10.2540.3170.5551
S20.3290.2450.4276
S30.3180.2160.4058
S40.2590.2450.4862
S50.3040.2120.4117
S60.2820.2310.4505
S70.2910.2720.4833
S80.2710.2250.4534
), ArticleFig(id=1201106665601983024, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1200860509521170546, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
No.5-HTNEOFTTSTFSTOverall rating
PeakrPeakrPeakrPeakrPeakrPeakr
1P50.342P10.602P80.559P160.857**P40.471P20.662
2P20.341P130.509P130.48P250.762*P50.376P40.612
3P120.264P40.433P240.31P200.745*P120.330P130.539
4P10.240P270.400P30.308P330.722*P110.299P250.318
5P40.189P60.392P250.244P340.706P20.286P330.257
6P30.177P250.392P10.239P230.670P90.283P30.254
7P60.138P330.374P200.168P140.660P310.261P60.229
8P70.063P320.364P60.152P240.641P70.225P120.209
9P220.049P340.357P20.151P100.639P170.179P280.159
10P240.034P110.333P300.148P290.405P60.177P80.132
), ArticleFig(id=1201106665786532418, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1200860509521170546, language=CN, label=Table 2, caption=

Pearson analysis results of common peaks and pharmacodynamic index of Baihe Dihuang decoction. r: Correlation coefficient; *P < 0.05, **P < 0.01

, figureFileSmall=null, figureFileBig=null, tableContent=
No.5-HTNEOFTTSTFSTOverall rating
PeakrPeakrPeakrPeakrPeakrPeakr
1P50.342P10.602P80.559P160.857**P40.471P20.662
2P20.341P130.509P130.48P250.762*P50.376P40.612
3P120.264P40.433P240.31P200.745*P120.330P130.539
4P10.240P270.400P30.308P330.722*P110.299P250.318
5P40.189P60.392P250.244P340.706P20.286P330.257
6P30.177P250.392P10.239P230.670P90.283P30.254
7P60.138P330.374P200.168P140.660P310.261P60.229
8P70.063P320.364P60.152P240.641P70.225P120.209
9P220.049P340.357P20.151P100.639P170.179P280.159
10P240.034P110.333P300.148P290.405P60.177P80.132
), ArticleFig(id=1201106665903972940, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1200860509521170546, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
No.5-HTNEOFTTSTFSTOverall rating
PeakrPeakrPeakrPeakrPeakrPeakr
1P330.694P40.683P10.658P20.672P330.671P20.589
2P20.655P10.657P80.637P330.655P20.67P10.575
3P10.654P20.641P30.616P10.618P50.643P330.553
4P250.638P60.598P250.605P250.608P40.638P30.432
5P230.631P250.591P230.603P340.595P10.638P250.418
6P340.624P330.59P340.603P320.594P250.635P50.410
7P210.623P300.586P60.602P190.591P70.635P230.407
8P300.623P210.586P320.602P30.591P80.633P80.406
9P190.623P140.585P20.602P290.590P190.632P130.404
10P320.621P190.585P190.601P210.590P140.631P70.403
), ArticleFig(id=1201106666071745112, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1200860509521170546, language=CN, label=Table 3, caption=

Grey relational analysis results of common peaks and pharmacodynamic index of Baihe Dihuang decoction

, figureFileSmall=null, figureFileBig=null, tableContent=
No.5-HTNEOFTTSTFSTOverall rating
PeakrPeakrPeakrPeakrPeakrPeakr
1P330.694P40.683P10.658P20.672P330.671P20.589
2P20.655P10.657P80.637P330.655P20.67P10.575
3P10.654P20.641P30.616P10.618P50.643P330.553
4P250.638P60.598P250.605P250.608P40.638P30.432
5P230.631P250.591P230.603P340.595P10.638P250.418
6P340.624P330.59P340.603P320.594P250.635P50.410
7P210.623P300.586P60.602P190.591P70.635P230.407
8P300.623P210.586P320.602P30.591P80.633P80.406
9P190.623P140.585P20.602P290.590P190.632P130.404
10P320.621P190.585P190.601P210.590P140.631P70.403
), ArticleFig(id=1201106667254538858, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1200860509521170546, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
Efficacy indexR2XR2YQ2VIP > 1
5-HT0.8220.9890.642P9, P6, P2, P25, P4, P12, P16, P17, P20, P3, P27, P24, P7, P13, P15, P18
NE0.9810.8590.634P6, P4, P3, P25, P23, P1, P33, P13, P5, P8
OFT0.7470.6620.545P2, P8, P25, P16, P13, P3, P7, P1, P24, P6, P20, P4, P22, P12, P5, P10
TST0.9390.6900.431P33, P1, P23, P34, P25, P21, P30, P14, P26, P2
FST0.8880.6960.449P2, P33, P1, P3, P5, P25, P13, P8, P6, P30, P7, P11
Overall rating0.9620.9710.940P2, P33, P1, P3, P25, P5, P8, P13, P6, P23, P7
), ArticleFig(id=1201106667476836978, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1200860509521170546, language=CN, label=Table 4, caption=

OPLS analysis results of common peaks and pharmacodynamic index of Baihe Dihuang decoction. OPLS: Orthogonal partial least squares discriminate analysis; VIP: Variable importance in the projection; R2X: Cumulative explained variance for independent variables; R2Y: Cumulative explained variance for response variables; Q2: Cumulative explained variance in cross validation

, figureFileSmall=null, figureFileBig=null, tableContent=
Efficacy indexR2XR2YQ2VIP > 1
5-HT0.8220.9890.642P9, P6, P2, P25, P4, P12, P16, P17, P20, P3, P27, P24, P7, P13, P15, P18
NE0.9810.8590.634P6, P4, P3, P25, P23, P1, P33, P13, P5, P8
OFT0.7470.6620.545P2, P8, P25, P16, P13, P3, P7, P1, P24, P6, P20, P4, P22, P12, P5, P10
TST0.9390.6900.431P33, P1, P23, P34, P25, P21, P30, P14, P26, P2
FST0.8880.6960.449P2, P33, P1, P3, P5, P25, P13, P8, P6, P30, P7, P11
Overall rating0.9620.9710.940P2, P33, P1, P3, P25, P5, P8, P13, P6, P23, P7
), ArticleFig(id=1201106667632026237, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1200860509521170546, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
Efficacy indexPearsonGRAOPLSPearson ∩ GRA ∩ OPLS
5-HTP5, P2, P12, P1, P4P33, P2, P4, P25, P23P9, P6, P2, P25, P4P4, P2
NEP1, P13, P4, P27, P6P4, P1, P2, P6, P25P4, P6, P3, P25, P23P4, P6
OFTP8, P13, P24, P3, P25P1, P8, P3, P25, P23P2, P8, P25, P16, P13P8, P25
TSTP16, P25, P20, P33, P34P2, P33, P1, P25, P34P33, P1, P23, P34, P25P33, P25, P34
FSTP4, P5, P12, P11, P2P33, P2, P5, P4, P1P2, P33, P1, P3, P5P2, P5
Overall ratingP2, P4, P13, P25, P33P2, P1, P33, P3, P25P2, P33, P1, P3, P25P2, P25, P33
), ArticleFig(id=1201106667791409808, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1200860509521170546, language=CN, label=Table 5, caption=

Comparison of three spectrum-effect correlation analysis. ∩: Intersection; GRA: Grey relational analysis

, figureFileSmall=null, figureFileBig=null, tableContent=
Efficacy indexPearsonGRAOPLSPearson ∩ GRA ∩ OPLS
5-HTP5, P2, P12, P1, P4P33, P2, P4, P25, P23P9, P6, P2, P25, P4P4, P2
NEP1, P13, P4, P27, P6P4, P1, P2, P6, P25P4, P6, P3, P25, P23P4, P6
OFTP8, P13, P24, P3, P25P1, P8, P3, P25, P23P2, P8, P25, P16, P13P8, P25
TSTP16, P25, P20, P33, P34P2, P33, P1, P25, P34P33, P1, P23, P34, P25P33, P25, P34
FSTP4, P5, P12, P11, P2P33, P2, P5, P4, P1P2, P33, P1, P3, P5P2, P5
Overall ratingP2, P4, P13, P25, P33P2, P1, P33, P3, P25P2, P33, P1, P3, P25P2, P25, P33
), ArticleFig(id=1201106667921433241, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1200860509521170546, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
PeaktR/minSourceCompoundFormula[M-H]-ErrorFragment ion MS2
DetectExpect
P23.00RRCatalpol #C15H22O10361.124 3361.125 01.93199.060 1, 181.051 2, 169. 052 5
P44.03RRMelittosideC21H33O15523.167 2523.165 72.86361.047 4, 343.048 1, 179. 050 8
P54.18RRLeonurideC15H24O9347.134 8347.136 34.32329.103 0, 303.110 0, 181.053 2, 167.032 6, 143.025 5, 113.026 5
P64.74LBRegaloside C#C18H24O11415.123 6415.124 0-1.20253.080 7, 235.059 4, 179.033 1, 161.022 8, 135.143 2
P810.52RRRehmannioside DC27H42O20685.219 7685.217 13.79505.248 0, 341.056 5, 323.035 6, 263.017 5, 221.024 3
P2525.18LBRegaloside a#C18H24O10399.129 6399.128 62.51163.039 3, 145.028 7, 119.049 3
P3337.30LBRegaloside b#C20H26O11441.140 4441.139 12.95399.130 6, 381.119 0, 163.039 4, 145.028 7, 119.049 4
P3439.05RRIsoacteoside #C29H36O15623.198 3623.197 02.09461.167 2, 315.110 1, 179.034 2, 161.023 7, 135.044 3
), ArticleFig(id=1201106668043068067, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1200860509521170546, language=CN, label=Table 6, caption=

Identification of 8 chemical components of Baihe Dihuang decoction. #: Confirmed by comparison with the reference substance. LB: Lilii Bulbus; RR: Rehmanniae radix

, figureFileSmall=null, figureFileBig=null, tableContent=
PeaktR/minSourceCompoundFormula[M-H]-ErrorFragment ion MS2
DetectExpect
P23.00RRCatalpol #C15H22O10361.124 3361.125 01.93199.060 1, 181.051 2, 169. 052 5
P44.03RRMelittosideC21H33O15523.167 2523.165 72.86361.047 4, 343.048 1, 179. 050 8
P54.18RRLeonurideC15H24O9347.134 8347.136 34.32329.103 0, 303.110 0, 181.053 2, 167.032 6, 143.025 5, 113.026 5
P64.74LBRegaloside C#C18H24O11415.123 6415.124 0-1.20253.080 7, 235.059 4, 179.033 1, 161.022 8, 135.143 2
P810.52RRRehmannioside DC27H42O20685.219 7685.217 13.79505.248 0, 341.056 5, 323.035 6, 263.017 5, 221.024 3
P2525.18LBRegaloside a#C18H24O10399.129 6399.128 62.51163.039 3, 145.028 7, 119.049 3
P3337.30LBRegaloside b#C20H26O11441.140 4441.139 12.95399.130 6, 381.119 0, 163.039 4, 145.028 7, 119.049 4
P3439.05RRIsoacteoside #C29H36O15623.198 3623.197 02.09461.167 2, 315.110 1, 179.034 2, 161.023 7, 135.044 3
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基于谱效关系及活性验证的百合地黄汤抗抑郁成分研究
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胡超 1 , 赵洪庆 2 , 刘检 1 , 王璐 1 , 杨磊 1 , 张水寒 3 , 唐林 1, *
药学学报 | 研究论文 2024,59(5): 1364-1373
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药学学报 | 研究论文 2024, 59(5): 1364-1373
基于谱效关系及活性验证的百合地黄汤抗抑郁成分研究
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胡超1, 赵洪庆2, 刘检1, 王璐1, 杨磊1, 张水寒3, 唐林1, *
作者信息
  • 1.湖南中医药大学第一附属医院, 湖南 长沙 410007
  • 2.湖南中医药大学科技创新中心, 湖南 长沙 410208
  • 3.湖南省中医药研究院, 湖南 长沙 410208

通讯作者:

*唐林, Tel: 86-731-85600544, E-mail:
Spectrum-effect relationship combined with bioactivity evaluation to discover the main antidepressant active components of Baihe Dihuang decoction
Chao HU1, Hong-qing ZHAO2, Jian LIU1, Lu WANG1, Lei YANG1, Shui-han ZHANG3, Lin TANG1, *
Affiliations
  • 1. The First Hospital of Hunan University of Chinese Medicine, Changsha 410007, China
  • 2. Technology Innovation Center, Hunan University of Chinese Medicine, Changsha 410208, China
  • 3. Hunan Academy of Chinese Medicine, Changsha 410208, China
出版时间: 2024-05-12 doi: 10.16438/j.0513-4870.2023-1184
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摘要
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本研究通过谱效相关分析及活性验证探明百合地黄汤抗抑郁的药效成分。利用不同溶剂分次提取并结合HPLC和UHPLC-MS分析方法对百合地黄汤不同提取部位化学成分进行全面表征。动物实验方案经湖南中医药大学动物伦理委员会审查通过(审查号为LLBH-202104270001), 所有程序均严格按照动物使用和护理的伦理原则进行。采用旷场实验、悬尾实验、强迫游泳实验等经典行为学方法结合神经递质测定进行抗抑郁药效综合评价。整合三种相关分析方法进行谱效关联表征, 以三种关联分析所得药效成分的交集为潜在药效成分, 并进行了体外细胞实验验证。研究发现, 王百合苷A、B、C、梓醇和异毛蕊花糖苷可能是百合地黄汤发挥抗抑郁作用的主要药效物质, 同时也提示, 多元化的谱效相关分析及活性验证有助于提升谱效相关分析结果的准确性。

百合地黄汤  /  抑郁症  /  谱效关系  /  活性验证  /  熵权-TOPSIS法  /  HPLC指纹图谱  /  多指标药效评价

The study utilized spectral correlation analyses combined with bioactivity evaluation to examine the effective components of antidepressants in the Baihe Dihuang decoction. Firstly, the chemical fingerprints for different extraction parts in the Baihe Dihuang decoction were achieved using HPLC and UHPLC-MS technology. Then, in order to evaluate the antidepressant effect of Baihe Dihuang decoction, the animal experimental protocol has been reviewed and approved by Laboratory Animal Ethics Committee of Hunan University of Chinese Medicine (No. LLBH-202104270001), in compliance with the Institutional Animal Care Guidelines. We recorded the distance of autonomous movement of mice in open field experiment, the immobility time of tail suspension test, and the forced swimming. Additionally, we measured the content of neurotransmitters. Finally, Pearson analysis, grey correlation analysis, and orthogonal partial least squares regression analysis were utilized to establish the correlation between antidepressant efficacy indicators and fingerprinting. The spectrum-effect relationship results were confirmed through the in vitro activity verification. This study demonstrated that regaloside A, B, C, catalpol, and Isoacteoside might be the main antidepressant components in Baihe Dihuang decoction. Furthermore, it was found that using diverse mathematical models and bioactivity evaluation could enhance the accuracy of the spectral correlation analyses results.

Baihe Dihuang decoction  /  depression  /  spectrum-effect relationship  /  activity verification  /  entropy-TOPSIS  /  HPLC fingerprint  /  multi-index efficacy evaluation
胡超, 赵洪庆, 刘检, 王璐, 杨磊, 张水寒, 唐林. 基于谱效关系及活性验证的百合地黄汤抗抑郁成分研究. 药学学报, 2024 , 59 (5) : 1364 -1373 . DOI: 10.16438/j.0513-4870.2023-1184
Chao HU, Hong-qing ZHAO, Jian LIU, Lu WANG, Lei YANG, Shui-han ZHANG, Lin TANG. Spectrum-effect relationship combined with bioactivity evaluation to discover the main antidepressant active components of Baihe Dihuang decoction[J]. Acta Pharmaceutica Sinica, 2024 , 59 (5) : 1364 -1373 . DOI: 10.16438/j.0513-4870.2023-1184
正文
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抑郁症是一种由多种因素(遗传、社会环境、生活事件和应激等) 引起的高发病率、高致死率、易复发的情感性精神障碍类疾病[1]。根据世界卫生组织预测, 全世界患有抑郁症的人群达到逾3.5亿, 每年因抑郁症自杀的死亡人数高达100万。由于2019年新冠疫情给人们生活工作带来的巨大压力, 抑郁症人群仍在持续快速增加[2]。目前西医治疗抑郁症药效有限且存在头痛、药物依赖等诸多不良反应难以克服。中医药治疗抑郁症历史悠久, 以其多成分、多靶点及不良反应小的优势, 越来越受到关注。百合地黄汤是治疗抑郁症的经典名方, 其临床疗效已获得广泛认同。目前研究表明, 百合地黄汤主要化学成分有皂苷类、苯乙醇苷类、环烯醚萜类等[3], 但化学成分与抗抑郁作用相关性缺乏系统研究, 其药效物质基础尚不明确, 极大地制约了该方的质量控制与临床应用。
谱效关系指在中医药理论现代研究的基础上, 以中药指纹图谱为基础, 以效应学为主要研究内容, 应用生物信息学方法, 建立中药指纹图谱与中药药效关系的一门学科。通过将能反映中药的化学指纹图谱信息与药效信息关联, 筛选出与药效关系密切的特征性成分, 为阐明中药药效物质基础提供新思路[4]。谱效相关分析用于中药复方研究, 能同时快速辨识多个有效成分, 对于中药多组分的复杂体系, 体现出多、快、好、省的优势。且该方法符合中医药整体观点, 有利于揭示中药多成分多靶点的协同作用特征[5]。近年来, 谱效关系研究已广泛应用于中药及其复方制剂药效物质、质量控制、炮制机制研究等方面[4, 5]。然而谱效关系研究目前主要仍有以下问题亟待解决: 如何选择合适的分析方法进行“谱”的全面表征？如何整合多种药理指标进行“效”的精准表达？如何运用多元化的化学计量学方法构建可靠的谱效关联数学模型？如何对谱效相关分析结果进行合理验证？本研究采用多部位提取结合UHPLC-MS技术进行中药化学指纹图谱全面表征、熵权-TOPSIS法优化整合多指标药效评价、多元化相关分析方法构建百合地黄汤谱效关系研究模型、同时结合细胞实验进行谱效相关成分活性验证, 以期初步阐明百合地黄汤抗抑郁主要药效成分, 为百合地黄汤的质量控制和临床应用提供参考依据。
材料与方法
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仪器   UltiMate 3000型超高效液相色谱仪和Q-Exactive Orbitrap质谱仪(美国赛默飞公司), 1260 Infinity Ⅱ高效液相色谱仪(美国安捷伦公司), AE240型电子天平[梅特勒-托利多仪器(上海) 有限公司], SMART 3.0动物行为学视频分析系统(西班牙Panlab公司), L530R台式低速冷冻离心机(湘仪), Enspire功能酶标仪(美国Perkinelmer公司), LSM800激光共聚焦显微镜(德国Zeiss公司); TG16W微量高速离心机(长沙湘智离心机仪器有限公司); Galaxy170RCO2二氧化碳培养箱(德国Eeppendorf公司); MSX-2细胞成像分析系统(广州明美科技有限公司)。
药品与试剂   文拉法辛胶囊(爱尔兰Pfizer Ireland Pharmaceuticals, 批号CN3193D)。百合饮片(批号20200801, 产地湖南龙山)、生地黄饮片(批号20200901, 产地河南焦作) 均由湖南南国药都中药饮片有限公司生产, 经湖南中医药大学第一附属医院制剂中心张裕民教授鉴定分别为百合科植物卷丹Lilium lancifolium Thunb.的干燥肉质鳞叶、玄参科植物地黄Rehmannia glutinosa Libosch.的干燥块根, 符合中国药典(一部, 2020年版) 的相关规定。王百合苷B (230039-202005, 纯度 > 98%)、王百合苷C (230056-202103, 纯度 > 98%)、王百合苷A (230051-202011, 纯度 > 98%) 均购自上海鸿永生物科技有限公司, 梓醇(110808-202112, 纯度 > 98%)、异毛蕊花糖苷(AF20020026, 纯度 > 98%) 购自成都埃法生物科技有限公司, 地黄苷A (批号D08302103003, 纯度 > 98%) 购自西安汇林生物科技有限公司, 毛蕊花糖苷(111530-201914, 纯度 > 98%) 购自中国食品药品检定研究院。小鼠5-羟色胺ELISA (enzyme linked immunosorbent assay) 试剂盒(2205M11) 和小鼠去甲肾上腺素(2205M16) ELISA试剂盒均为江苏菲亚生物科技有限公司生产。
实验动物   SPF级ICR小鼠100只, 雌雄各半, 体质量18~20 g, 购自湖南斯莱克景达实验动物有限公司, 使用许可证号: SYXK (湘) 2019-0009; 动物生产许可证号: SCXK (湘) 2019-0004; 实验方案经湖南中医药大学动物伦理委员会审查通过(审查号为LLBH-202104270001), 所有程序均严格按照动物使用和护理的伦理原则进行。
样品制备   取百合150 g和生地黄150 g, 重复4份, 分别加入10倍量55%乙醇、75%乙醇、95%乙醇及纯化水, 加热回流提取2次, 提取时间分别为1.5、1 h, 滤过后将滤液减压浓缩回收乙醇, 真空冷冻干燥, 得到冻干粉, 即得S1 (55%乙醇)、S2 (75%乙醇)、S3 (95%乙醇)、S4 (水部位)。另采用醇水双提法以使药物提取完全, 即取百合150 g和生地黄150 g, 加入6倍量75%乙醇回流提取2次, 时间分别为1.5、1 h, 合并滤液得醇提液。药渣加入10倍量水煎煮2次, 时间分别为1.5、1 h, 合并滤液得水提液。醇提液减压回收乙醇至无醇味, 与水提液合并, 减压浓缩得到药液, 依次用氯仿、乙酸乙酯、正丁醇进行萃取, 得到4个不同提取部位的提取物, 分别挥干有机溶剂后冷冻干燥, 即得S5 (氯仿部位)、S6 (乙酸乙酯部位)、S7 (正丁醇部位)、S8 (剩余水部位)。
色谱及质谱条件   Kromasil C18色谱柱(250 mm × 4.6 mm, 5 μm); 流动相为0.1%甲酸水溶液(A)-乙腈(B); 梯度洗脱: 0~10 min, 3%~5% A; 10~20 min, 5%~15% A; 20~30 min, 15%~17% A; 30~40 min, 17%~25% A; 40~45 min, 25% A。流速1.0 mL·min-1, 进样量20 μL, 柱温30 ℃。检测波长: 0~15 min, 210 nm; 15~45 min, 315 nm。运用四极杆飞行时间串联质谱仪进行分析与鉴定。采用负离子模式, 电喷雾离子源(ESI源)。毛细管电压3.5 kV, 离子传输毛细管温度400 ℃, 离子源温度375 ℃, 辅助气流速10 arb。相对分子质量扫描范围m/z 100~1 200。
对照品溶液制备   精密称取对照品梓醇、王百合苷C、王百合苷A、毛蕊花糖苷、王百合苷B、异毛蕊花糖苷、地黄苷A各1 mg, 分别置于10 mL量瓶中, 加甲醇定容至刻度, 过0.22 μm微孔滤膜, 取续滤液, 备用。
供试品溶液制备   分别称取百合地黄汤8种不同提取部位冻干粉, 用70%甲醇超声(功率100 W, 频率40 kHz) 30 min, 配制成质量浓度为生药20 mg·mL-1的供试品溶液, 过0.22 μm微孔滤膜, 取续滤液, 备用。
方法学验证   精密度实验: 取供试品溶液适量, 重复进样6次, 记录峰面积。稳定性实验: 制备百合地黄汤供试品溶液适量, 室温分别放置0、2、4、8、12、24 h后进样检测, 记录峰面积。重复性实验: 取同一百合地黄冻干粉, 制备百合地黄汤供试品溶液6份进样分析。
动物分组及给药[6, 7]   100只SPF级ICR小鼠适应性喂养7天, 随机分为正常组、百合地黄汤不同提取部位组(S1、S2、S3、S4、S5、S6、S7、S8)、文拉法辛对照组, 每组10只。正常组: 每日1次给予蒸馏水灌胃; 药物组: 百合地黄不同提取部位给予该方临床等效2倍剂量(8 g·kg-1), 每日1次; 文拉法辛对照组: 文拉法辛溶于生理盐水, 给予临床等效2倍剂量(19.5 mg·kg-1), 每日1次。给药剂量按体表面积比率换算, 均给药7天。给药期间每组小鼠分笼饲养, 随意饮水, 食用标准动物饲料。
行为学测定   旷场实验、悬尾实验、强迫游泳实验用于评价百合地黄汤不同提取部位对小鼠抑郁样行为的调节作用。①旷场实验: 将小鼠放入80 cm × 80 cm × 40 cm的黑色敞箱中央, 自由活动30 s后, 分别记录5 min内的小鼠自主活动总距离。②强迫游泳实验: 将各组小鼠放入专用强迫游泳筒(水深约25 cm) 中, 记录其5 min内不动(以两前爪不动、身体呈漂浮状态视为不动) 时间。③悬尾实验: 将各组小鼠尾部用胶布固定于同一高度, 记录其5 min内不动(以身体垂直倒立、四爪紧缩视为不动) 时间。
ELISA测定各组脑组织5-HT、NE含量   神经递质假说是抑郁症发病机制的经典假说。5-HT、NE与抑郁症的发生发展密切相关。取适量冻存的脑组织加生理盐水匀浆, 3 000 r·min-1离心10 min, 取上清液。采用ELISA测定各组脑组织5-羟色胺(5-hydroxytryptamine, 5-HT)、去甲肾上腺素(norepinephrine, NE) 水平, 严格按照ELISA试剂盒说明书进行操作。
抗抑郁药效指标综合评价[8-10]   采用SPSSAU (20.0版。北京清思科技有限公司) 进行百合地黄汤不同提取部位抗抑郁药效指标熵权-TOPSIS综合评价。首先根据熵权法计算各指标权重系数。其次采用TOPSIS法对百合地黄汤抗抑郁药效指标进行综合评价, 将权重系数与初始矩阵相乘得到加权矩阵, 计算得出最优方案以及最劣方案, 计算每个样品与最优最劣方案的距离, 得到相对接近度, 以此排序, 相对接近度越大表明综合评价越好。
原始数据无量纲处理   在系统中由于各因素的物理意义不同, 导致数据量纲上的不统一, 便于比较, 在进行关联分析时, 一般需将原始数据进行无量纲化, 采用归一化法, 按公式(1) 或(2) 进行无纲量化处理。
$ {Y}_{ij}=\frac{{X}_{ij}-{X}_{\mathrm{m}\mathrm{i}\mathrm{n}}}{{X}_{\mathrm{m}\mathrm{a}\mathrm{x}}-{X}_{\mathrm{m}\mathrm{i}\mathrm{n}}} $
$ {Y}_{ij}=\frac{{X}_{\mathrm{m}\mathrm{a}\mathrm{x}}-{X}_{ij}}{{X}_{\mathrm{m}\mathrm{a}\mathrm{x}}-{X}_{\mathrm{m}\mathrm{i}\mathrm{n}}} $
公式(1) 适用于正向指标, 公式(2) 适用于负向指标。Yij为无量纲化数据, Xij为原始数据, Xmin为该组数据的最小值, Xmax为该组数据的最大值。
Pearson相关性分析   Pearson分析是一种参数方法, 被广泛用于衡量变量之间的线性关系。本研究将8种提取物的色谱数据和抗抑郁药效指标数据导入SPSS 23.0分析软件, 然后采用Pearson分析相关性。以百合地黄汤S1~S8共有峰峰面积为自变量, 药效指标为因变量, 通过Pearson相关性分析计算两者之间的Pearson相关系数。Pearson相关系数被用于衡量2个变量之间的线性关系, Pearson相关系数越大, 相关性越强。分别计算出各共有色谱峰与药效指标之间的Pearson相关系数。
灰色关联度分析   灰色关联关系分析法是一种评价两个系统的因素在不同时间或不同对象之间的相似或差异程度的方法。可以用来分析多个变量和多个因素之间的关联性。本研究采用SPSSAU (20.0版。北京清思科技有限公司) 分析抗抑郁药效指标与S1~S8共有峰之间的相关性, 并找出与药效指标相对应的主要活性成分。分别将5-HT、NE等药效指标作为母序列, 百合地黄汤不同提取部位共有峰峰面积作为子序列, 计算关联度, 关联度越高, 成分与抗抑郁药效指标关联性越强。
正交偏最小二乘法分析   OPLS (orthogonal partial least squares discriminate analysis) 是一种改进的偏最小二乘法分析方法, 适用于小样本, 能克服多变量共线性的问题, 处理干扰数据, 提高模型的解释性和预测的可靠性。以百合地黄汤不同提取部位共有峰峰面积为自变量(X), 以各药效指标数据为因变量(Y), 利用X-Y数据集在SIMCA-P (14.1版) 中建立OPLS模型, 然后根据变量投影重要性(variable importance in the projection, VIP) 值(≥1) 和相关系数(正相关) 筛选出主要活性化合物。
关联成分液质分析   为了解谱效相关各色谱峰的化学结构信息, 在上述色谱条件及质谱条件下, 对供试品及对照品溶液进行分析, 根据各色谱峰在正/负离子模式下获得的准分子离子, 并结合相关文献对图谱中关联成分的可能化学结构进行推测。
海马神经元细胞原代培养   取孕16或17日SPF级SD大鼠, 75%酒精消毒, 取胎鼠置于冰盒上, 体视显微镜下快速取其全脑, 分离出海马, 备用; 将海马组织块剪碎, 加入等体积的0.25%胰酶与0.2%胶原酶消化15 min, 用含10% FBS的DMEM/F12完全培养基终止消化, 重悬细胞, 200目筛网中过滤, 1 000 r·min-1转速离心5 min; 弃上清液, 200目重悬过筛后重悬细胞, 接种于96孔或24孔细胞培养板中, 置于37 ℃、5% CO2二氧化碳细胞培养箱中培养, 4 h全量换液为含2% B27、1% L-GlutaMAX及1%双抗的Neurobasal无血清培养基, 5~7天后便可用于后续实验。
细胞实验造模、分组及给药   待上述原代海马神经元细胞培养至5~7天时, 参照文献[11]方法采用200 μmol·L-1皮质酮干预复制模拟抑郁症环境的体外细胞模型, 并将培养的细胞随机分为: 正常组、模型组、阳性药组、王百合苷A、王百合苷B、王百合苷C、梓醇、异毛蕊花糖苷, 除正常组和模型组给予等量的培养基外, 其他组在造模的同时, 阳性药组给予1×10-6 mol·L-1的文拉法辛, 其余各受试药给予1×10-6 mol·L-1的相应药物, 继续干预作用海马神经元细胞24 h后, 进行各项指标检测。
细胞形态学检测   原代海马神经元经造模及相应药物干预处理后, 采用细胞成像分析技术分别检测各组中海马神经元的基本形态结构变化。
细胞凋亡检测   原代海马神经元经造模及相应药物干预处理后, 弃液, PBS洗2次, 海马神经元细胞用4%多聚甲醛固定35 min后, PBS洗2次, 加入Hoechst 33258工作液, 室温、避光孵育20 min, PBS洗3次, 最后采用激光共聚焦显微镜上进行蓝色的凋亡荧光检测, 并观察各组海马神经元细胞凋亡情况。
突触损伤情况检测   原代海马神经元经造模及相应药物干预处理后, 弃液, PBS洗2次, 海马神经元细胞分别经4%多聚甲醛固定35 min、0.25% Triton-100处理15 min后, PBS洗2次; 加入FITC-FJB工作液(20 μL的0.2%的FJB母液+ 10 mL的0.1%的醋酸溶液), 4 ℃避光孵育60 min, 弃液, PBS洗5次; 加入DAPI工作液, 室温、避光孵育20 min, PBS洗3次后, 最后于激光共聚焦显微镜上进行荧光检测, 并观察海马神经元细胞形态及树突、树突棘等神经元突触损伤情况。
神经递质检测   经造模及相应药物干预处理后, 各组按严格要求收集细胞上清液, 采用酶联免疫吸附法(ELISA), 并严格参照试剂盒说明书步骤, 检测各组细胞培养液上清中神经递质5-HT、NE含量。
统计学分析   采用SPSS23.0软件进行数据的统计分析, 如符合正态分布的数据, 用单因素方差分析(one-way ANOVA), 其中若方差齐, 两两比较采用最小显著差法(LSD), 方差不齐则采用Dunnett's T3检验行两两比较; 如不符合正态分布, 则用非参数检验进行统计分析, 所有数据均用$ \stackrel{-}{x} $ ± s表示, 以P < 0.05、P < 0.01代表有统计学差异。
结果
收起
1 百合地黄汤不同提取部位HPLC指纹图谱
建立了百合地黄汤不同提取部位样品HPLC色谱图, 如图 1所示, 共标记35个共有峰。精密度实验共有峰峰面积相对标准偏差(RSD) 在0.03%~2.58%, 表明仪器精密性良好。稳定性实验0~24 h共有峰峰面积RSD在0.07%~2.50%, 表明该条件下供试品溶液在24 h内稳定。重复性实验共有峰的平均峰面积RSD在0.72%~3.00%之间, 表明该实验方法重复性良好。
2 百合地黄汤不同提取部位对小鼠抑郁样行为及5-HT、NE的影响
旷场实验、悬尾实验、强迫游泳实验结果见图 2A~C, 与正常对照组比较, S2、S7组小鼠自主活动距离显著增加(P < 0.01或P < 0.05); S2、S3、S5、S6组小鼠的悬尾实验不动时间显著减小(P < 0.01或P < 0.05); S1、S3、S4、S6组小鼠的强迫游泳不动时间显著减小(P < 0.01或P < 0.05)。综上, 百合地黄汤不同提取部位均可改善小鼠抑郁样行为, 其中S8作用最弱, 对悬尾实验及强迫游泳不动时间、旷场实验自主活动距离均无显著调节作用。S2、S3作用较强, S2对悬尾实验不动时间、旷场实验自主活动距离均有显著调节作用, S3对悬尾实验及强迫游泳不动时间具有显著调节作用。
百合地黄汤不同提取部位对小鼠脑组织5-HT、NE的作用结果见图 2D、E, 结果表明, 与正常对照组比较, S1、S2、S5、S6、S7、S8组小鼠脑组织5-HT显著增加(P < 0.05或P < 0.01), S4、S6、S7组小鼠脑组织NE值显著增加(P < 0.05)。综上, 百合地黄汤不同提取部位均有较好的调节神经递质的作用, 其中S3作用最弱, 对5-HT、NE两种神经递质均无显著调节作用。S6、S7作用较强, 对5-HT、NE两种神经递质具有显著调节作用。
3 百合地黄汤不同提取部位抗抑郁药效指标综合评价
通过熵权法计算得5-HT、NE、旷场实验总活动距离、悬尾实验不动时间、强迫游泳实验不动时间的权重系数分别为19.77%、19.55%、19.94%、17.19%、23.55%。其次采用TOPSIS法对百合地黄汤抗抑郁药效指标进行综合评价, 结果见表 1, 结果表明, 百合地黄汤S1、S4、S7综合评价最高, 百合地黄汤S3综合评价最低。
4 谱效相关分析百合地黄汤抗抑郁药效成分
Pearson相关系数被用于衡量2个变量之间的线性关系, Pearson相关系数越大, 相关性越强。分别计算出各共有色谱峰与药效指标之间的Pearson相关系数。由表 2可知, 各药效指标与共有色谱峰具有一定相关性, 其中悬尾实验不动时间与P16、P25、P20、P33相关系数较高, 且具有显著性差异(P < 0.01或P < 0.05), 综合评价关联系数前5的色谱峰分别为P2、P4、P13、P25、P33。
灰色关联度的结果见表 3, 各药效指标关联度排名前10共有峰与药效指标关联度均 > 0.4, 其中综合评价关联度前5的色谱峰为P2、P1、P33、P3、P25, 其中2号峰的关联度最大。
在OPLS模型中, 通常用R2和Q2来评价模型的成功与否。R2代表模型的解释能力, 而Q2代表模型的预测能力。表 4显示了每个药效指标的OPLS模型参数, 结果表明不同药效指标回归模型拟合解释能力以及模型预测能力均较强。应用OPLS分析, 化学成分VIP值越大, 表示该成分对药效的影响越大, 本研究选择VIP大于1的成分作为药效指标关联成分, 结果见表 4。其中综合评价VIP前5的色谱峰为P2、P33、P1、P3、P25, 其中P2号峰VIP最大。
每种谱效相关分析方法都有其局限性和适应性。在以往的研究中, 一般采用单一的谱效关联分析来研究有多个指标的实际问题, 其结果往往有一定的偏差。为了得到更科学、更可靠的结果, 本研究对上述三个谱效相关分析结果取交集, 结果如表 5所示, 共有峰P2、P4、P5、P6、P8、P25、P33、P34被认为是百合地黄汤中主要的抗抑郁谱效相关成分。
5 关联成分液质分析
采用Thermo Scientific Xcalibur (4.1.50) 来分析百合地黄汤提取物的质谱信息。通过将保留时间与分子离子峰在负离子模式下的高分辨率质谱数据能够确定化合物的分子量。然后通过对二次碎片、参考文献信息和相关文献数据的分析确定碎片离子规律。最后, 通过整合精确的分子量、碎片离子和文献数据来确定化合物的结构。部分共有峰通过对照品进行成分确定(图 1)。本研究共确定8个关联峰并明确关联峰所代表化学成分, 其化学信息详见表 6。
6 关联成分活性验证
细胞形态学测定结果如图 3A所示, 细胞成像分析检测结果显示, 与正常组比较, 皮质酮诱导后的模型组原代海马神经元细胞明显受损, 神经网络断裂, 胞体收缩或破裂, 树突及其分支减少; 与模型组比较, 文拉法辛、王百合苷A、王百合苷B、王百合苷C、梓醇均能不同程度改善皮质酮诱导的海马神经元细胞损伤, 其中以王百合苷B、王百合苷C及梓醇作用效果最佳, 但异毛蕊花糖苷对损伤的海马神经元细胞修复作用较弱或基本无效, 以上提示百合地黄汤中王百合苷A、王百合苷B、王百合苷C、梓醇4个成分是有效保护皮质酮诱导所致的海马神经元细胞损伤的主要成分。
细胞凋亡检测结果如图 3B所示, 与正常组比较, 皮质酮诱导后的模型组原代海马神经元凋亡细胞数明显增多, 细胞核浓染, 核皱缩, 染色质聚集; 与模型组比较, 文拉法辛、王百合苷B、王百合苷C、梓醇、异毛蕊花糖苷均能不同程度抑制皮质酮诱导的海马神经元细胞凋亡, 其中以王百合苷B、王百合苷C、梓醇效果最佳, 但王百合苷A抑制海马神经元细胞凋亡作用较弱, 这提示百合地黄汤中王百合苷B、王百合苷C、梓醇、异毛蕊花糖苷4个成分是抑制海马神经元凋亡进而保护皮质酮诱导所致的海马神经元细胞损伤的主要成分。
突触损伤测定结果如图 3C所示, 与正常组比较, 皮质酮诱导后的模型组原代海马神经元内尼氏小体减少, 树突及神经网络断裂, 呈明显的突触损伤; 与模型组比较, 文拉法辛、王百合苷A、王百合苷B、王百合苷C、梓醇、异毛蕊花糖苷均能不同程度改善皮质酮诱导的海马神经元突触损伤, 其中以王百合苷B、王百合苷C和梓醇作用效果最佳, 这提示百合地黄汤中王百合苷A、B、C、梓醇、异毛蕊花糖苷5个成分是改善海马神经元突触损伤的主要成分。
神经递质测定结果如图 3D所示, 与正常组比较, 皮质酮诱导后的模型组神经元细胞上清液中神经递质5-HT、NE水平明显降低(P < 0.01或P < 0.05); 与模型组比较, 王百合苷A、B、C能显著提升神经递质5-HT、NE水平(P < 0.01或P < 0.05), 王百合苷C能显著提升神经递质5-HT、NE水平(P < 0.01或P < 0.05), 梓醇、异毛蕊花糖苷也能显著增加神经递质NE水平。以上说明, 百合地黄汤中调控神经递质的主要活性成分为百合的王百合苷A、B、C, 以及地黄的梓醇和异毛蕊花糖苷, 这可能是百合地黄汤改善抑郁症的重要机制之一。
讨论
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百合地黄汤化学成分包含皂苷等极性较大的成分, 也包含苯乙醇苷等极性小的分子化合物, 单一提取方法难以表征其全部化学信息, 本研究采用不同溶剂分次提取并结合HPLC和UHPLC-MS分析方法对百合地黄汤不同提取部位化学成分进行了全面表征, 相较单一有效部位的指纹表征, 多部位化学成分表征更能体现中药成分的系统性和复杂性, 更能解决中药指纹图谱难以反映中药不同提取部位化学成分多样性的问题, 有利于中药谱效相关分析“谱”的全面表征。
旷场实验、悬尾实验、强迫游泳实验均是经典的抑郁样行为学实验, 具有操作简单快捷、实验动物敏感的优点, 常用于抗抑郁药物的药效初筛及动物抑郁样行为的评价[6]。神经递质假说是抑郁症发病机制的经典假说, 5-HT、NE等神经递质与抑郁症的发生发展密切相关。5-HT是抑制性神经递质, 在大脑皮层和神经突触中呈高表达, 在调节情绪状态、学习记忆、活动节律等方面发挥重要作用, 其水平在抑郁症患者中枢神经系统中显著降低[12, 13]。NE可在神经末梢突触间发挥作用, 具有影响神经可塑性, 调节机体认知、情绪、疼痛等生理功能, 其水平在抑郁症患者脑内显著降低, 从而导致NE系统功能障碍, 导致患者记忆认知功能受损, 产生抑郁情绪[12, 13]。因此, 本实验中采用经典行为学方法结合神经递质进行抗抑郁药效综合评价。相比较单一药效指标评价, 综合评价能更加准确、全面体现中药的药理作用。但各指标间的权重系数一直困扰着综合评价。传统的多指标综合评价方法多采用专家咨询法, 具有一定的主观性。熵权法通过计算熵值来判断一个指标的分散程度, 指标的离散程度越大, 对综合评价的影响就越大, 其权重系数就越大。因此, 熵权法基于对实验数据的充分分析, 减少了主观因素对实验结果的干扰, 提升了多指标综合评价的科学性和合理性, 可为中药复方多靶点药效评价提供参考[9, 10]。本研究中采用熵权法对行为学及神经递质评价指标进行权重分析, 确定综合评价各指标的权重系数, 结果表明基于熵权法的综合评价能客观、准确、合理确定各指标的权重系数, 解决了综合评价药效指标赋权主观性强、数据分析不充分的问题, 有利于中药谱效相关分析“效”的精准表达。
化学计量学分析是中药谱效研究的重要环节。许多统计方法被应用于谱效相关性研究, 包括相关分析、聚类分析、回归分析、灰色关联分析及图谱比对分析等。Pearson分析能够简化信息, 是一种常用的相关性分析方法, 能够从整体上分析变量间的关系, 更符合中药作用的整体性[14]; 灰色关联度分析是目前中药谱效关系分析中最常用的分析方法。与其他分析方法相比, 灰色关联度分析要求数据较少, 对数据要求低, 更加适合复杂成分中药谱效关系的研究。但灰色关联度分析只能阐明各指纹峰与药效指标的关联性大小, 无法描述各指纹峰对药效指标的相互作用[15, 16]。回归分析是通过建立回归方程来探讨各成分对药效贡献率及各成分对药效的综合作用。其中偏最小二乘法在建立数学模型时排除了自变量多重线性的干扰从而应用最广, 可同时实现数据结构简化、相关分析及回归建模的统计学方法, 能最大限度地利用有限数据信息, 并具有较高的预测性[17, 18]。每一种统计分析都有其局限性和适应性。本研究采用上述三种分析方法进行谱效相关分析, 取三种关联分析药效成分的交集为潜在药效成分, 结果表明, 三种分析方法所得有效成分有一定差别, 但也有共性成分, 取共性成分为潜在药效成分, 解决单一方法造成的谱效关联偏差, 有利于谱效相关分析结果合理性和准确性。
海马神经元在学习记忆和情绪中起着重要作用, 与抑郁症密切相关。研究发现, 神经元的功能障碍可能导致抑郁症[19], 海马体积的减少是焦虑抑郁症的一个关键神经解剖学特征且抑郁症患者的神经元损伤标记物显著升高[20]。动物研究表明, 具有抑郁样行为大鼠的海马神经元树突棘密度显著降低[21]。因此, 神经元突触数量减少、突触结构变化被认为是抑郁症发病机制之一。本研究中, 王百合苷A、B、C、梓醇和异毛蕊花糖苷能不同程度改善皮质酮诱导所致的海马神经元细胞形态结构改变及突触损伤, 并显著抑制海马神经元凋亡, 能不同程度调控神经递质水平, 提示王百合苷A、B、C、梓醇和异毛蕊花糖苷是百合地黄汤发挥有效抗抑郁作用的主要药效物质, 同时改善海马神经元损伤及神经递质异常是百合地黄汤抗抑郁的重要机制。
综上所述, 本研究采用“多部位成分谱表征-多指标药效整合-多元化数据分析”构建百合地黄汤抗抑郁部位谱效关系, 并经活性验证发现王百合苷A、B、C、梓醇和异毛蕊花糖苷可能是百合地黄汤发挥抗抑郁作用的主要药效成分。该研究为百合地黄汤的质量控制和临床应用提供实验依据。但百合地黄汤谱效关联成分的药理作用有待进一步体内实验验证, 成分间相互作用机制有待进一步挖掘, 课题组后续将对各成分进行深层次药理机制验证与研究。
作者贡献: 胡超负责数据库构建、样品测试及文章撰写; 赵洪庆、王璐负责样品制备及动物实验; 刘检负责细胞实验; 杨磊负责数据分析指导, 张水寒负责课题监管、文章审阅及技术指导。唐林负责课题监管、文章撰写、文章审阅及技术指导。
利益冲突: 所有作者均声明不存在利益冲突。
基金
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  • 湖南省自然科学基金项目(2022JJ80093)
  • 湖南省自然科学基金项目(2023JJ60132)
  • 湖南省自然科学基金项目(2022JJ80094)
  • 湖南省教育厅科学研究项目(22B0362)
  • 湖南省卫生健康委科研计划项目(202213055417)
  • 湖南省中医药科研计划项目(B2023054)
  • 湖南中医药大学中药粉体与创新药物省部共建国家重点实验室培育基地开放基金(2022FTKFJJ11)
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参考文献 引证文献
排序方式：
[1]
Wray NR, Ripke S, Mattheisen M, et al. Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression [J]. Nat Genet, 2018, 50: 668-681.
[2]
Buckner JD, Abarno CN, Lewis EM, et al. Increases in distress during stay-at-home mandates during the COVID-19 Pandemic: a longitudinal study [J]. Psychiatry Res, 2021, 298: 113821.
[3]
Zhao YT, Zhang ZL, Li XJ, et al. Research progress of classic prescription Baihe Dihuang decoction [J]. J Guangdong Pharm Univ (广东药科大学学报), 2022, 38: 137-142.
[4]
Li S, Wang ZY, Chang HJ, et al. Establishment of HPLC fingerprint and effects of antioxidant and radioresistance related to its spectrum study of Aucklandiae Radix [J]. Chin Tradit Herb Drugs (中草药), 2023, 54: 2580-2587.
[5]
Liu X, Yu H, Song JT, et al. Integration of plasma metabolomics and spectrum-effect correlation for profiling the mechanism and pharmacodynamic substances on attenuating hepatic fibrosis of Bupleuri Radix and Paeoniae Radix Alba before and after vinegar-processing and compatibility [J]. Acta Pharm Sin (药学学报), 2023, 58: 1790-1801.
[6]
Jiang N, Zhang YW, Yao CH, et al. Overview of animal behavioral tests of depression [J]. Acta Lab Anim Sci Sin (中国实验动物学报), 2021, 29: 830-838.
[7]
Tang L, Zhao HQ, Yang H, et al. Optimization of extraction process of polysaccharide from Baihe dihuang decoction and study on its antianxiety and anti-depression efficacy [J]. China Pharm (中国药房), 2023, 34: 923-928.
[8]
Feng LM, Chen YY, Yue SJ, et al. Quantitative identification of TCM Q-markers based on analytical hierarchy and the entropy weight comprehensive method by taking Shaoyao Gancao decoction as an example [J]. Acta Pharm Sin (药学学报), 2021, 56: 296-305.
[9]
Tang L, Lu AJ, Wang L, et al. Optimization of the molding process of Zhiyangrunfu Cream [J]. Chin Tradit Pat Med (中成药), 2022, 44: 3614-3418.
[10]
Wu HW, Li DH, Zhang YG, et al. Comprehensive quality evaluation of Astragali Radix processed by different methods based on entropy weight TOPSIS model [J]. Chin Pharm J (中国药学杂志), 2021, 56: 1325-1331.
[11]
Liu J, Liu L, Tang L, et al. Protective effects and mechanism of Zuogui Jiangtang Jieyu Formulation on hippocampal neuron of NVU induced by autophagy in diabetes mellitus with depression [J]. Chin Tradit Herb Drugs (中草药), 2019, 50: 2420-2427.
[12]
Tian P, Zhang W, Li KY, et al. Effect of Rehmanniae Radix on depression-like behavior and hippocampal monoamine neurotransmitters of chronic unpredictable mild stress model rats [J]. China J Chin Mater Med (中国中药杂志), 2022, 47: 4691-4697.
[13]
Tao J, Zhou M, Wang YT, et al. The antidepressant effect of myricetin and its regulatory mechanism on neurotransmitters [J]. Chin Tradit Pat Med (中成药), 2021, 43: 3195-3198.
[14]
Wang ZY, Yang SY, Lv W, et al. Analysis of spectrum-activity relationship among antioxidant parts of Lycii Fructus using three different chemometrics methods [J]. China J Chin Mater Med (中国中药杂志), 2021, 46: 3377-3387.
[15]
Wang Y, Peng X, He YL, et al. Spectrum-effect relationship of anti-inflammatory active components from nonvolatile fraction of Blumea balsamifera based on gray correlation analysis [J]. Chin J Exp Tradit Med Form (中国实验方剂学杂志), 2019, 25: 180-186.
[16]
Lin MY, Zhang YP, Li Y, et al. Spectra-effect relationship of anti-inflammation of Salvia miltiorrhiza extract based on gray correlation analysis [J]. Chin Tradit Herb Drugs (中草药), 2017, 48: 3447-3452.
[17]
Peng LY, Liang Y, Shi JJ, et al. Relationship between HPLC fingerprint and total antioxidant activity of Danshen [J]. Pharmacol Clin Chin Mater Med (中药药理与临床), 2022, 38: 110-115.
[18]
Sun F, Wu XQ, Qi Y, et al. Application of partial least squares algorithm to explore bioactive components of crude and stir-baked hawthorn for invigorating spleen and promoting digestion [J]. China J Chin Mater Med (中国中药杂志), 2023, 48: 958-965.
[19]
Lee SH, Kim NS, Choi M, et al. LGI1 governs neuritin-mediated resilience to chronic stress [J]. Neurobiol Stress, 2021, 15: 100373.
[20]
Willard SL, Riddle DR, Forbes ME, et al. Cell number and neuropil alterations in subregions of the anterior hippocampus in a female monkey model of depression [J]. Biol Psychiatry, 2013, 74: 890-897.
[21]
Pacheco A, Aguayo FI, Aliaga E, et al. Chronic stress triggers expression of immediate early genes and differentially affects the expression of AMPA and NMDA Subunits in dorsal and ventral hippocampus of rats [J]. Front Mol Neurosci, 2017, 10: 244.
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doi: 10.16438/j.0513-4870.2023-1184
  • 接收时间：2023-10-19
  • 首发时间：2025-11-27
  • 出版时间：2024-05-12
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  • 收稿日期：2023-10-19
  • 修回日期：2023-12-28
基金
湖南省自然科学基金项目(2022JJ80093)
湖南省自然科学基金项目(2023JJ60132)
湖南省自然科学基金项目(2022JJ80094)
湖南省教育厅科学研究项目(22B0362)
湖南省卫生健康委科研计划项目(202213055417)
湖南省中医药科研计划项目(B2023054)
湖南中医药大学中药粉体与创新药物省部共建国家重点实验室培育基地开放基金(2022FTKFJJ11)
作者信息
    1.湖南中医药大学第一附属医院, 湖南 长沙 410007
    2.湖南中医药大学科技创新中心, 湖南 长沙 410208
    3.湖南省中医药研究院, 湖南 长沙 410208

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2种不同金属材料的力学参数
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Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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