Article(id=1256183440383328785, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1256183358493679805, articleNumber=null, orderNo=null, doi=10.13193/j.issn.1673-7717.2025.12.002, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=null, receivedDateStr=null, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1777427070947, onlineDateStr=2026-04-29, pubDate=1765296000000, pubDateStr=2025-12-10, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1777427070947, onlineIssueDateStr=2026-04-29, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1777427070947, creator=13701087609, updateTime=1777427070947, updator=13701087609, issue=Issue{id=1256183358493679805, tenantId=1146029695717560320, journalId=1255847919539208197, year='2025', volume='43', issue='12', pageStart='1', pageEnd='258', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=1, specialIssue=null, createTime=1777427051344, creator=13701087609, updateTime=1777427760067, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1256186331126969089, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1256183358493679805, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1256186331126969090, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1256183358493679805, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=5, endPage=14, ext={EN=ArticleExt(id=1256183444330168900, articleId=1256183440383328785, tenantId=1146029695717560320, journalId=1255847919539208197, language=EN, title=Research Progress on Chemical Constituents,Pharmacological Effects and Clinical Application of Classic Prescription on Baizhu Powder(白术散)and Predictive Analysis on lts Q-Markers, columnId=1256183423710970242, journalTitle=Chinese Archives of Traditional Chinese Medicine, columnName=New Opinion of Ph.D. Supervisor, runingTitle=null, highlight=null, articleAbstract=

Baizhu Powder(白术散)is a classic prescription for invigorating spleen and nourishing stomach from Xiaoer Yaozheng Zhijue.Modern studies show that ithas the functions of regulating intestinal microecology,reducing inflammation,antiviral effect,regulating blood sugar,improving insulin resistance,protecting liver,etc.It is commonly used clinically to treat diarrhea of children,anorexia,auxiliary treatment of diabetes,hyperlipidemia,etc.On the basis of summarizing the research progress of chemical composition,pharmacological action and clinical application of Baizhu Powder,the prediction analysis was carried out according to the“five principles”of quality marker(Q-Marker).The results showed that ginsenosides Rg1,Rb1,Re,atractylenolideⅠ,Ⅱ,Ⅲ,puerarin,daidzin,daidzein,patchouli alcohol,dehydrocostus lactone,costunolide,liquiritin(SH),glycyrrhizic acid,dehydrotumulosic acid and polyporenic acid C,can be considered as Q-Markers for Baizhu Powder,and this study can provide reference for the quality control of Baizhu Powder.

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白术散出自《小儿药证直诀》,是补脾养胃的经典名方。现代研究表明,其具备调节肠道微生态、减轻炎症反应、抗病毒、调节血糖、改善胰岛素抵抗、保肝等药理作用,临床常用于治疗小儿腹泻、厌食症,并辅助治疗糖尿病、高脂血症等。在总结白术散的化学成分、药理作用及临床应用研究进展的基础上,依照中药质量标志物(Quality Marker,QMarker)“五原则”进行预测分析,结果表明人参皂苷(Rg1、Rb1、Re)、白术内酯(Ⅰ、Ⅱ、Ⅲ)、葛根素、大豆苷、大豆苷元、百秋李醇、去氢木香内酯、木香烃内酯、甘草苷、甘草酸、去氢土莫酸、猪苓酸C可作为白术散的Q-Marker,为白术散的质量控制提供参考依据。

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臧振中(1979-),男,河南周口人,副教授,硕士研究生导师,博士,研究方向:中药制造新工艺和新装备。E-mail:
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管咏梅(1979-),女,河南周口人,教授,博士研究生导师,博士,研究方向:中药新制剂与新技术。

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管咏梅(1979-),女,河南周口人,教授,博士研究生导师,博士,研究方向:中药新制剂与新技术。

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管咏梅(1979-),女,河南周口人,教授,博士研究生导师,博士,研究方向:中药新制剂与新技术。

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UPLC法测定葛根中9个化学成分的含量[J]. 现代中药研究与实践202438(2):48-52., articleTitle=UPLC法测定葛根中9个化学成分的含量, refAbstract=null), Reference(id=1256183522193228374, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1256183440383328785, doi=null, pmid=null, pmcid=null, year=2012, volume=21, issue=15, pageStart=28, pageEnd=29, url=null, language=null, rfNumber=[147], rfOrder=146, authorNames=张宏武, 程雪宁, 魏建和, journalName=中国药业, refType=null, unstructuredReference=张宏武,程雪宁,魏建和,. 海南广藿香药材中百秋李醇和广藿香酮的含量测定[J]. 中国药业201221(15):28-29., articleTitle=海南广藿香药材中百秋李醇和广藿香酮的含量测定, refAbstract=null), Reference(id=1256183522700739159, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1256183440383328785, doi=null, pmid=null, pmcid=null, year=2015, volume=35, issue=11, pageStart=1946, pageEnd=1952, url=null, language=null, rfNumber=[148], rfOrder=147, authorNames=胡益杰, 刘爽, 邓丽娜, journalName=药物分析杂志, refType=null, unstructuredReference=胡益杰,刘爽,邓丽娜,. 川木香药材HPLC指纹图谱及含量测定方法研究[J]. 药物分析杂志201535(11):1946-1952., articleTitle=川木香药材HPLC指纹图谱及含量测定方法研究, refAbstract=null), Reference(id=1256183522860122712, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1256183440383328785, doi=null, pmid=null, pmcid=null, year=2020, volume=18, issue=9, pageStart=1507, pageEnd=1512, url=null, language=null, rfNumber=[149], rfOrder=148, authorNames=陈素娥, 孙红, 朱琳, journalName=中南药学, refType=null, unstructuredReference=陈素娥,孙红,朱琳,. 茯苓药材高效液相色谱指纹图谱及多指标成分定量研究[J]. 中南药学202018(9):1507-1512., articleTitle=茯苓药材高效液相色谱指纹图谱及多指标成分定量研究, refAbstract=null), Reference(id=1256183523015311961, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1256183440383328785, doi=null, pmid=null, pmcid=null, year=2023, volume=40, issue=7, pageStart=47, pageEnd=52, url=null, language=null, rfNumber=[150], rfOrder=149, authorNames=刘梅清, 冯晓莉, 刘媛媛, journalName=中医药信息, refType=null, unstructuredReference=刘梅清,冯晓莉,刘媛媛,. 不同土质和生长年限甘草HPLC指纹图谱及3种成分含量测定研究[J]. 中医药信息202340(7):47-52., 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化合物类别化合物名称归属参考文献
单萜、倍半萜及其内酯类β-人参烯、古芸烯、吉玛烯、β-古芸烯、人参醇、α-杜松醇、斯巴醇、薄荷醇、松油烯、异龙脑、芳樟醇、柠檬烯、苍术酮、β-桉油醇、白术内酯Ⅰ*、白术内酯Ⅱ*、白术内酯Ⅲ*、双白术内酯、α-广藿香烯、β-广藿香烯、广藿香半缩酮、愈创木烯、百秋李醇*、刺蕊草烯、Senecrassidiol、蒎烯、金合欢烯、β-木香酸、木香醇、桉叶醇、木香内酯、去氢木香内酯*、木香烃内酯*、广木香醇、蛇麻烯、榄香烯、雪松烯、石竹烯、川木香内酯、樟脑、茴香脑人参、茯苓、白术、木香、广藿香[13202641-452046-49]
三萜、三萜皂苷类人参皂苷Rb1*、Rb2、Rc、Re*、Rf、Rg1*、Ro、RT2、RT3,茯苓酸,猪苓酸C,去氢土莫酸,茯苓新酸A,茯苓新酸B,去氢茯苓酸,齐墩果酸,木香二内酯,白桦脂醇,α-香树脂醇,鲨烯,甘草次酸,甘草酸*,apioglycyrrhizin,18-甘草酸,甘草皂苷A3,苦葛皂苷D,苦葛皂苷E,粉葛皂苷Ⅱ,粉葛皂苷Ⅲ人参、茯苓、木香、甘草、葛根[43150-58]
黄酮类芹菜素、刺槐素、藿香苷、异藿香苷、田蓟苷、金丝桃苷、刺甘草查尔酮、芹糖甘草苷、异甘草苷、甘草苷*、夏佛托苷、佛来心苷、光甘草酮、新异甘草苷、甘草查尔酮B、甘草素、异甘草素、lobatflflavate、新葛根甲素、毛蕊异黄酮、芒果苷、毛蕊异黄酮苷、poulobaoneA、补骨脂宁、大豆苷*、大豆苷元*、葛根素*甘草、葛根、广藿香[3359-65]
多糖类PC3、PC-PS、PCR-Ⅰ、PC-Ⅱ、PCP、ATPCP、AMAP-1、AMAP-2、AMAP-3、葛根多糖、人参多糖茯苓、白术、甘草、葛根、人参[61366-68]
苯丙素类Agastionl、Agastenol、毛蕊花糖苷、列当苷、黄药苷广藿香[69]
蛋白质、氨基酸、肽类半胱氨酸、天冬氨酸、鸟氨酸、组氨酸过氧化氢酶、蛋白激酶、谷氨酸、丝氨酸人参、茯苓、甘草、木香、[1170-71]
), ArticleFig(id=1256183498772234542, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1256183440383328785, language=CN, label=表1, caption=

白术散组方中药化学成分信息表

, figureFileSmall=null, figureFileBig=null, tableContent=
化合物类别化合物名称归属参考文献
单萜、倍半萜及其内酯类β-人参烯、古芸烯、吉玛烯、β-古芸烯、人参醇、α-杜松醇、斯巴醇、薄荷醇、松油烯、异龙脑、芳樟醇、柠檬烯、苍术酮、β-桉油醇、白术内酯Ⅰ*、白术内酯Ⅱ*、白术内酯Ⅲ*、双白术内酯、α-广藿香烯、β-广藿香烯、广藿香半缩酮、愈创木烯、百秋李醇*、刺蕊草烯、Senecrassidiol、蒎烯、金合欢烯、β-木香酸、木香醇、桉叶醇、木香内酯、去氢木香内酯*、木香烃内酯*、广木香醇、蛇麻烯、榄香烯、雪松烯、石竹烯、川木香内酯、樟脑、茴香脑人参、茯苓、白术、木香、广藿香[13202641-452046-49]
三萜、三萜皂苷类人参皂苷Rb1*、Rb2、Rc、Re*、Rf、Rg1*、Ro、RT2、RT3,茯苓酸,猪苓酸C,去氢土莫酸,茯苓新酸A,茯苓新酸B,去氢茯苓酸,齐墩果酸,木香二内酯,白桦脂醇,α-香树脂醇,鲨烯,甘草次酸,甘草酸*,apioglycyrrhizin,18-甘草酸,甘草皂苷A3,苦葛皂苷D,苦葛皂苷E,粉葛皂苷Ⅱ,粉葛皂苷Ⅲ人参、茯苓、木香、甘草、葛根[43150-58]
黄酮类芹菜素、刺槐素、藿香苷、异藿香苷、田蓟苷、金丝桃苷、刺甘草查尔酮、芹糖甘草苷、异甘草苷、甘草苷*、夏佛托苷、佛来心苷、光甘草酮、新异甘草苷、甘草查尔酮B、甘草素、异甘草素、lobatflflavate、新葛根甲素、毛蕊异黄酮、芒果苷、毛蕊异黄酮苷、poulobaoneA、补骨脂宁、大豆苷*、大豆苷元*、葛根素*甘草、葛根、广藿香[3359-65]
多糖类PC3、PC-PS、PCR-Ⅰ、PC-Ⅱ、PCP、ATPCP、AMAP-1、AMAP-2、AMAP-3、葛根多糖、人参多糖茯苓、白术、甘草、葛根、人参[61366-68]
苯丙素类Agastionl、Agastenol、毛蕊花糖苷、列当苷、黄药苷广藿香[69]
蛋白质、氨基酸、肽类半胱氨酸、天冬氨酸、鸟氨酸、组氨酸过氧化氢酶、蛋白激酶、谷氨酸、丝氨酸人参、茯苓、甘草、木香、[1170-71]
), ArticleFig(id=1256183499212636469, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1256183440383328785, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
化合物名称分子式CAS相对分子质量来源
人参皂苷Rg1(Ginsenoside Rg1C42H72O1422427-39-0801.01人参
人参皂苷Rb1(Ginsenoside Rb1C54H92O2341753-43-91 109.29人参
人参皂苷Re(Ginsenoside Re)C48H82O1851542-56-4947.15人参
白术内酯Ⅰ(Atractylenolide-1)C15H18O273069-13-3230.30白术
白术内酯Ⅱ(Atractylenolide-2)C15H20O273069-14-4232.32白术
白术内酯Ⅲ(Atractylenolide-3)C15H20O373030-71-4248.32白术
葛根素(Puerarin)C21H20O93681-99-0416.38葛根
大豆苷(Daidzin)C21H20O9552-66-9416.38葛根 甘草
大豆苷元(Daidzein)C15H10O4486-66-8254.24葛根 甘草
百秋李醇(Patchouli alcohol)C15H26O5986-55-0222.37广藿香
去氢木香内酯(Dehydrocostus lactone)C15H18O2477-43-0230.30木香
木香烃内酯(Costunolide)C15H20O2553-21-9232.32木香
甘草苷(Liquiritin SH)C21H22O9551-15-5418.40甘草
甘草酸(Glycyrrhizic acid)C42H62O161405-86-3822.94甘草
去氢土莫酸(Dehydrotumulosic acid)C31H48O46754-16-1484.71茯苓
猪苓酸C(Polyporenic acid C)C31H46O4465-18-9482.69茯苓
), ArticleFig(id=1256183499351048503, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1256183440383328785, language=CN, label=表2, caption=

白术散的Q-Marker信息

, figureFileSmall=null, figureFileBig=null, tableContent=
化合物名称分子式CAS相对分子质量来源
人参皂苷Rg1(Ginsenoside Rg1C42H72O1422427-39-0801.01人参
人参皂苷Rb1(Ginsenoside Rb1C54H92O2341753-43-91 109.29人参
人参皂苷Re(Ginsenoside Re)C48H82O1851542-56-4947.15人参
白术内酯Ⅰ(Atractylenolide-1)C15H18O273069-13-3230.30白术
白术内酯Ⅱ(Atractylenolide-2)C15H20O273069-14-4232.32白术
白术内酯Ⅲ(Atractylenolide-3)C15H20O373030-71-4248.32白术
葛根素(Puerarin)C21H20O93681-99-0416.38葛根
大豆苷(Daidzin)C21H20O9552-66-9416.38葛根 甘草
大豆苷元(Daidzein)C15H10O4486-66-8254.24葛根 甘草
百秋李醇(Patchouli alcohol)C15H26O5986-55-0222.37广藿香
去氢木香内酯(Dehydrocostus lactone)C15H18O2477-43-0230.30木香
木香烃内酯(Costunolide)C15H20O2553-21-9232.32木香
甘草苷(Liquiritin SH)C21H22O9551-15-5418.40甘草
甘草酸(Glycyrrhizic acid)C42H62O161405-86-3822.94甘草
去氢土莫酸(Dehydrotumulosic acid)C31H48O46754-16-1484.71茯苓
猪苓酸C(Polyporenic acid C)C31H46O4465-18-9482.69茯苓
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经典名方白术散化学成分、药理作用、临床应用研究进展及质量标志物预测分析
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管咏梅 1, 2 , 郝凌烽 1 , 王智权 2 , 王丹凤 2 , 吴样明 2 , 付佳宁 1, 2 , 臧振中 1
中华中医药学刊 | 博士导师新论 2025,43(12): 5-14
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中华中医药学刊 | 博士导师新论 2025, 43(12): 5-14
经典名方白术散化学成分、药理作用、临床应用研究进展及质量标志物预测分析
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管咏梅1, 2, 郝凌烽1, 王智权2, 王丹凤2, 吴样明2, 付佳宁1, 2, 臧振中1
作者信息
  • 1.江西中医药大学现代中药制剂教育部重点实验室,江西 南昌 330004
  • 2.经典名方现代中药创制全国重点实验室,江西 南昌 330004
  • 管咏梅(1979-),女,河南周口人,教授,博士研究生导师,博士,研究方向:中药新制剂与新技术。

通讯作者:

臧振中(1979-),男,河南周口人,副教授,硕士研究生导师,博士,研究方向:中药制造新工艺和新装备。E-mail:
Research Progress on Chemical Constituents,Pharmacological Effects and Clinical Application of Classic Prescription on Baizhu Powder(白术散)and Predictive Analysis on lts Q-Markers
Yongmei GUAN1, 2, Lingfeng HAO1, Zhiquan WANG2, Danfeng WANG2, Yangming WU2, Jianing FU1, 2, Zhenzhong ZANG1
Affiliations
  • 1.Key Laboratory of Modern Traditional Chinese Medicine Preparations,Ministry of Education,Jiangxi University of Chinese Medicine,Nanchang 330004,Jiangxi,China
  • 2.National Key Laboratory of Classic Formula and Modern Traditional Chinese Medicine Creation,Nanchang 330004,Jiangxi,China
出版时间: 2025-12-10 doi: 10.13193/j.issn.1673-7717.2025.12.002
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白术散出自《小儿药证直诀》,是补脾养胃的经典名方。现代研究表明,其具备调节肠道微生态、减轻炎症反应、抗病毒、调节血糖、改善胰岛素抵抗、保肝等药理作用,临床常用于治疗小儿腹泻、厌食症,并辅助治疗糖尿病、高脂血症等。在总结白术散的化学成分、药理作用及临床应用研究进展的基础上,依照中药质量标志物(Quality Marker,QMarker)“五原则”进行预测分析,结果表明人参皂苷(Rg1、Rb1、Re)、白术内酯(Ⅰ、Ⅱ、Ⅲ)、葛根素、大豆苷、大豆苷元、百秋李醇、去氢木香内酯、木香烃内酯、甘草苷、甘草酸、去氢土莫酸、猪苓酸C可作为白术散的Q-Marker,为白术散的质量控制提供参考依据。

白术散  /  质量标志物  /  五原则  /  临床应用  /  化学成分

Baizhu Powder(白术散)is a classic prescription for invigorating spleen and nourishing stomach from Xiaoer Yaozheng Zhijue.Modern studies show that ithas the functions of regulating intestinal microecology,reducing inflammation,antiviral effect,regulating blood sugar,improving insulin resistance,protecting liver,etc.It is commonly used clinically to treat diarrhea of children,anorexia,auxiliary treatment of diabetes,hyperlipidemia,etc.On the basis of summarizing the research progress of chemical composition,pharmacological action and clinical application of Baizhu Powder,the prediction analysis was carried out according to the“five principles”of quality marker(Q-Marker).The results showed that ginsenosides Rg1,Rb1,Re,atractylenolideⅠ,Ⅱ,Ⅲ,puerarin,daidzin,daidzein,patchouli alcohol,dehydrocostus lactone,costunolide,liquiritin(SH),glycyrrhizic acid,dehydrotumulosic acid and polyporenic acid C,can be considered as Q-Markers for Baizhu Powder,and this study can provide reference for the quality control of Baizhu Powder.

Baizhu Powder(白术散)  /  quality marker  /  five principles  /  pharmacological action  /  chemical composition
管咏梅, 郝凌烽, 王智权, 王丹凤, 吴样明, 付佳宁, 臧振中. 经典名方白术散化学成分、药理作用、临床应用研究进展及质量标志物预测分析. 中华中医药学刊, 2025 , 43 (12) : 5 -14 . DOI: 10.13193/j.issn.1673-7717.2025.12.002
Yongmei GUAN, Lingfeng HAO, Zhiquan WANG, Danfeng WANG, Yangming WU, Jianing FU, Zhenzhong ZANG. Research Progress on Chemical Constituents,Pharmacological Effects and Clinical Application of Classic Prescription on Baizhu Powder(白术散)and Predictive Analysis on lts Q-Markers[J]. Chinese Archives of Traditional Chinese Medicine, 2025 , 43 (12) : 5 -14 . DOI: 10.13193/j.issn.1673-7717.2025.12.002
白术散出自宋代钱乙的《小儿药证直诀》,由人参、茯苓、白术(土炒)、葛根、广藿香、木香、甘草7味中药组成,国家中医药管理局将白术散收录于《古代经典名方目录(第二批儿科部分)》。白术散方中人参补脾益肺、补气生津;茯苓健脾宁心、利水渗湿;白术健脾益气、燥湿利水,土炒后借土气助脾,补脾止泻力胜;葛根鼓舞胃气、生津止渴;广藿香和木香芳香醒脾和胃;甘草调和诸药;临床主治小儿脾胃虚弱、腹泻,并且对糖尿病、高脂血症等慢性病的治疗起辅助作用[1]。质量标志物(Q-Marker)由刘昌孝院士提出,主要由质量传递与溯源、成分特有性、有效性、可测性和复方配伍环境5个方面组成[2]。本文在对白术散的化学成分、药理作用、临床应用的研究进展进行总结的基础上,并基于“五原则”对白术散的Q-Marker进行预测分析,以期为白术散的质量控制和新药开发提供参考。
人参化学成分主要包括人参皂苷、挥发油、多糖、氨基酸和多种微量元素等[3]。人参皂苷是人参最重要的活性成分,也是主要的功效成分,广泛存在于人参的不同部位,大多属于三萜类皂苷,主要包括Rb1、Rb2、Re、Rd、Rg1等。挥发油约占人参化学成分的0.1% ~0.5%,主要由倍半萜、醇类、醛类等组成[4],研究人员应用气相色谱-质谱联用技术(gas chromatograph-mass spectrometer,GC-MS)测定人参挥发油中的化学成分,代表性成分包括β-人参烯、吉玛烯等[5]。多糖在人参化学成分中约占60%,主要由中性糖和酸性多糖组成,结构较复杂[6]。目前在人参中提取分离出15种氨基酸,以精氨酸比例最大,其次是谷氨酸[7]。除此之外,钠、镁、钾等微量元素也在人参中广泛存在[8]
茯苓富含萜类、多糖类、挥发油、蛋白质、氨基酸等化合物。茯苓的三萜类化合物大多属于四环三萜类化合物,包括猪苓酸C、去氢土莫酸等。此外,AKIHISA和UKIYA[9]还发现了二萜类化合物7-oxo-15-hydroxydehy-droabieticacid、dehydroabietic acid methyl ester。茯苓的多糖类成分,按结构分为β-茯苓聚糖和杂多糖,由葡萄糖、木糖和甘露糖等单糖聚合而成。研究者应用GC-MS技术检测茯苓挥发油成分,鉴定出104个化学成分,占茯苓挥发油总量的79.69%,包括d-杜松烯、α-衣兰油烯、α-紫穗槐烯等[10]。目前已知茯苓含有50多种蛋白质成分,包括过氧化氢酶、甘露醇脱氢酶、蛋白激酶等,还含有谷氨酸、天冬氨酸等氨基酸类成分[11]。而且,茯苓含有多种人体所需的微量元素,以铁含量最高[12]
白术的化学成分主要包括萜类、黄酮类、多糖类、氨基酸等。萜类是白术的重要活性成分,包括单帖、倍半萜、倍半萜内酯等,如白术内酯Ⅰ、Ⅱ、Ⅲ等[13]。白术挥发油多由单萜倍半萜组成,研究发现不同产地的白术挥发油中共有成分21种,均以苍术酮含量最高[14]。白术的黄酮类化学成分以黄酮、黄酮醇为主,如芹菜素、木犀草素等[15]。白术多糖具有多种药理作用,由葡萄糖、甘露糖、半乳糖、木糖等单糖组成[16]。此外,白术含有赖氨酸、组氨酸等氨基酸成分[17]
针对不同的临床需求,白术有多种炮制手段。经炮制后其主要化学成分含量会发生不同程度的变化,白术挥发油含量以生白术最高,清炒、麸炒、土炒白术次之,焦白术最低[18]。研究者采用高效液相色谱(high performance liquid chromatography,HPLC)串联紫外检测器分析白术不同炮制品中苍术酮,白术内酯Ⅰ、Ⅱ、Ⅲ的含量。与生品相比,苍术酮含量在白术不同炮制品中均降低,且以土炒白术含量最低;而白术内酯Ⅰ、Ⅱ、Ⅲ的含量均显著增加,且以土炒白术中白术内酯Ⅱ含量最高[19];白术散组方中为土炒白术,炮制后挥发油含量降低缓和燥性,同时借土气增强其补脾的功效。
广藿香富含萜类、黄酮类、苯丙素类、含氮化合物等化学成分。萜类在广藿香中广泛存在,目前已报道的57个萜类化学成分,包括广藿香烷型、愈创木烷型和广藿香醇型等[20]。单萜倍半萜是广藿香挥发油的主要组成成分,VERMA 等通过气相色谱 -火焰离子化检测器(gas chromatography-flame ionization detection,GC-FID)和GCMS对广藿香挥发油进行检测分析,百秋李醇(占挥发油成分的42.2%~57.7%)、α-布尼烯(9.0%~15.2%)、α-愈创木烯(6.4%~17.9%)等[21]。此外,ZHU H等[22]在广藿香挥发油成分中分离得到2个新的半缩酮倍半萜类化合物:PocahemiketalA和PocahemiketalB。黄酮类是广藿香非挥发性的主要成分,包括黄酮、黄酮醇、二氢黄酮等,如芹菜素、3-甲基槲皮素等[23]。广藿香中也有少量的苯丙素类成分,目前已知有毛蕊花糖苷、列当苷、黄药苷等[20]。同时,广藿香非挥发成分还有含氮化合物,如生物碱广藿香吡啶和表愈创吡啶[24]
木香的化学成分包括萜类、蒽醌类、黄酮类和氨基酸等。其中,单萜和倍半萜是木香挥发油的主要组成成分[25]。研究人员采用GC-MS分析木香挥发油成分,鉴定出54种成分,主要为萜类和内酯类化合物,其中去氢木香内酯、二氢去氢木香内酯、木香烃内酯含量较高,分别为39.13%、14.36%、2.75%[26]。木香中蒽醌、黄酮类成分相对较少,目前已知的蒽醌类成分有aloe-emodin-8-O-β-D-glucopyranoside和rhein-8-O-β-D-glucopyranoside等[27];黄酮类成分主要为含有酮式羰基的黄酮苷[28]。此外,木香还含有天冬氨酸、丝氨酸、甘氨酸、苯丙氨酸等多种氨基酸成分[29]
甘草的化学成分主要包括三萜皂苷类、黄酮类、多糖类等。目前已在甘草中检测出超过60种三萜皂苷类化合物,如甘草酸等[30]。研究人员[31]通过聚酰胺-大孔树脂柱色谱等多种柱色谱技术分离纯化甘草中的三萜皂苷类成分,获得了macedonoside A、uralsaponin C等10个齐墩果烷型五环三萜皂苷类化合物,其中包括2个新化合物licorice-saponin R3和licorice-saponin S3。黄酮类成分是甘草的主要活性成分,包括二氢黄酮类、异黄酮等[32]。徐曙等[33]采用多层柱层析和重结晶等技术,从甘草中分离出光甘草定、甘草素、异甘草素和甘草苷等黄酮类成分。甘草多糖是由葡萄糖、半乳糖和鼠李糖等单糖组成的杂多糖[34]。除此之外,马君义等[35]运用GC-MS首次分析了甘草的挥发性成分,主要包括2-甲基庚烷、3-甲基庚烷、庚烷等。目前,已有研究证明甘草含有人体所需的20种氨基酸[36]
葛根是一种传统的药食同源中药材,其主要化学成分包括黄酮类、三萜类、有机酸类和多糖类等。黄酮类成分既是葛根的特征性成分,也是葛根的主要有效成分,其结构多为异黄酮类,如葛根素、大豆苷、大豆苷元等。季鹏等[37]通过柱色谱以及HPLC技术首次分离出毛蕊异黄酮苷。葛根中的三萜类成分包括大豆皂醇(Soyasap-ogenol)、槐二醇(Sophoradiol)、刺槐皂苷Ⅲ(KaikasaponinⅢ)等[38]。史军杰[39]利用吸附树脂、正反相硅胶、凝胶柱层析等分离手段,在葛根中分离出2种新的有机酸类化合物,分别为4-O-β-D-吡喃葡萄糖氧基苯甲酸(4-O-β-D-glucopyranosyloxy Benzoic acid)和反式-对香豆酰基乙醇酸(trans-p-coumaroyl glycolic acid)。葛根多糖也是葛根中一类重要的营养成分,由鼠李糖、甘露糖和葡萄糖等单糖组成[40]。目前,葛根多糖的产品开发已成为研究热点之一,为葛根产业的发展赋予了新活力。
中药复方化学成分复杂,目前对白术散的化学成分研究多基于单味药的化学成分研究,尚未见对其全方化学成分的研究分析,基于以上对白术散组方单味药的研究,预测分析白术散全方化学成分主要包括单萜、倍半萜类、三萜类、皂苷类、黄酮类、多糖类、苯丙素类以及蛋白质、氨基酸、肽类等,具体成分见表1
白术散具有健脾养胃、益气生津的功效,中医临床主治脾胃虚弱、津虚内热证。现代研究表明白术散的药理作用主要包括调节肠道微生态、减轻炎症反应、抗病毒、调节血糖、改善胰岛素抵抗、保肝作用、提高免疫功能、促进细胞新生等。见插页Ⅰ图1
现代研究表明,白术散有利于酵母菌、乳杆菌、双歧杆菌等的增殖,可以调节纤维素酶、蛋白酶、木聚糖酶等的活性,具备改善肠道菌群失衡及肠道微生态的药理作用[72]。孙必强等[73]通过建立肠道菌群失调小鼠模型,并给予不同剂型白术散治疗,模型小鼠给药后肠道中肠球菌、肠杆菌、乳杆菌等菌群菌量均有增加,表明白术散能调节肠道菌群失调,增加有益菌数量。惠华英等[74]研究发现,抗生素所致小鼠腹泻模型给予白术散后,抗生素所致肠道炎症反应明显减轻,受损肠道黏膜组织得到修复,小鼠乳糖酶活性明显改善,腹泻症状消失,表明白术散对肠道乳糖酶具有改善作用,具有调节肠道微生态的药理作用。刘嘉欣[75]的研究表明,白术散可以使肠道微生物功能基因发生变化,如上调糖酵解关键限速酶6磷酸果糖激酶和丙酮酸激酶基因,从而增强糖酵解反应,使代谢过程释放更多能量,促进结肠重吸收水分和电解质,以此减轻腹泻症状。
白术散具有减轻炎症反应的药理作用,研究表明,白术散通过上调肠道黏膜上皮抑炎因子白细胞介素-4(interleukin-4,IL-4)和白细胞介素-10(interleukin-10,IL-10)的表达,下调干扰素-α(lnterferon-α,IFN-α)的表达,减少血清IFN-α和白细胞介素-6(interleukin-6,IL-6)的含量,减缓炎症反应[76-77]。刘仕琦等[78]通过实验研究发现,白术散可以显著降低糖尿病模型小鼠血清样本中的炎症因子TNF-α、IL-6、IL-1β水平。孙必强等[79]发现,白术散能够促进肠道黏膜上皮抑炎因子IL-4、IL-10的表达,抑制IFN-α的表达,从而减轻肠道的炎症反应。
研究表明,白术散可以下调Toll样受体4(toll-like receptors 4,TLR4)、核因子-κB(nuclear factor kappa-B,NF-κB)信号通路,抑制肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、TNF-γ、IL-6、脂肪酶(lipase,LPS)等的产生以及表达,激活磷脂酰肌醇3-激酶(phosphoinositide 3-kinase,PI3K)、蛋白激酶B(protein kinase B,AKt)等信号通路,使糖尿病模型大鼠空腹血糖水平显著降低,胰岛素抵抗指数下降,表明白术散具有调节血糖、改善胰岛素抵抗的药理作用[80-83]。研究人员以HepG2细胞建立胰岛素抵抗模型,给药白术散后,高中低浓度白术散均能不同程度改善模型细胞的葡萄糖指数,其作用机制与单磷酸腺苷激活的蛋白激酶(Adenosine5-monophosphate(AMP)-activated protein kinase,AMPK)、PI3K、AKT信号通路激活有关[84]。刘雪辉等[85]研究发现,白术散可以使2型糖尿病小鼠模型的体质量减轻,血糖、总胆固醇(TC)、甘油三酯(TG)、TNF-α、TNF-γ水平显著降低。王翠菊等[86]通过观察白术散对糖尿病大鼠肠道屏障以及炎症因子的影响,发现白术散能够上调肠道紧密连接蛋白occludin和ZO-1的表达,促进肠黏膜机械屏障修复,下调TLR4、NF-κB信号通路,减少IL-6、TNF-α等炎症因子释放,抑制LPS入血,从而修复肠道屏障功能,缓解机体炎症反应,调节血糖。
白术散具有抗病毒的药理作用,研究表明,白术散通过上调小肠黏膜iELCD3+T细胞核中依赖双链RNA的蛋白激酶(doublestranded RNA-dependent protein kinase,PKR)[87]和抗病毒蛋白2'-5'寡聚腺苷酸合成酶(2'-5'oligoadenylate synthetase,OAS)的表达,以及拮抗抑制剂Cenistein对OAS和PKR蛋白表达的抑制作用,增强抗病毒蛋白OAS和PKR协同作用,发挥抗病毒的药理作用[88]
研究发现,白术散可以显著改善谷丙转氨酶(alanine aminotransferase,ALT)、谷草转氨酶(aspartate aminotransferase,AST)水平,具有保肝作用。郝倩[89]通过实验研究发现,白术散可以显著降低T2DM大鼠的空腹血糖、血清游离脂肪酸(free fatty acid,FFA),减轻体质量,改善肝脏病理学形态、肝细胞气球样变,及血糖血脂水平和血清中ALT、AST水平。白术散还可以减轻肝组织炎症反应,王宪庆[90]通过实验研究表明白术散通过调节细胞因子IL-2、IL-8、TNF-α的表达,缓解肝组织炎症反应,从而降低血清中ALT、AST含量,以达到保肝的药理作用。
白术散还具有改善免疫功能,促进细胞生长的药理作用。肖新云等[91]经实验研究发现,菌群失调腹泻小鼠给药白术散后血小板数、红细胞平均体积和白细胞数均有显著增长,显著改善腹泻小鼠模型的免疫功能。白术散在MA104细胞单层上对病毒复制具有显著抑制作用,可以有效延长感染病毒细胞的存活时间,促进细胞生长增殖和感染细胞新生,表明白术散具有促进细胞生长和增殖的药理作用[92]
白术散被誉为“儿科之圣”,在小儿腹泻治疗中相较于西药具有疗效突出、复发率低、远期疗效突出的优势。廖世忠[93]用白术散治疗40例小儿脾虚型腹泻患者,给药治疗后总有效率为95%,高于蒙脱石散对照组,且复发率和不良反应均低于对照组,白术散发挥疗效途径可能与其具有较好的补脾养胃功效有关。林婉婷等[94]用白术散治疗体质量7.5 kg腹泻婴幼儿,服药1剂后,解稀便次数明显减少,服药5 d后,大便次数转1次/d,余症消失。临床上,白术散也常与中医传统疗法联合使用以治疗小儿脾虚型腹泻。张娟等[95]通过白术散和推拿联用治疗46例脾虚腹泻患儿,治疗总有效率为100%,患儿的D-木糖排泄率和尿淀粉酶活性均较治疗前改善,且各项指标均优于基础对症治疗组。张艳霞等[96]采用白术散加味联合脐灸针对性治疗40例腹泻型肠易激综合征患者,治疗后患者腹痛、腹泻时间、大便时伴随症状评分、肠道有益菌数量等均优于西药对照组。
轮状病毒感染会破坏肠道黏膜,导致肠道对水分和电解质的重吸收能力下降,水电解质代谢紊乱,肠道微生态失调,继而引发腹泻、肠炎等。谢丽等[97]联合使用白术散和蒙脱石散治疗45例轮状病毒性肠炎患儿,总有效率为93%,治疗后的腹泻、发热症状及肠道菌群数量等情况均优于常规治疗对照组。董潞潞[98]用白术散配合穴位贴敷治疗48例儿童轮状病毒感染性腹泻,治疗后的总有效率、临床症状缓减时间及大便性状改善时间均优于常规治疗对照组。李清等[99]将白术散联合西医常用药治疗小儿轮状病毒感染患儿60例,治疗后的总有效率及临床症状优于单用西药对照组,并推断其机制可能与白术散增强患儿消化吸收功能和肠道免疫功能有关。
白术散具有生津消渴、利水除湿的功效,主治津虚内热证。现代临床研究表明,白术散联合常规西药可以有效调节糖尿病患者血糖血脂水平,改善胰岛素抵抗,且具有不良反应少、复发率低的优势。梁嘉朗等[100]用白术散联合二甲双胍肠溶胶囊治疗40例肥胖2型糖尿病患者,总有效率为95%,空腹血糖与餐后2 h血糖均低于二甲双胍对照组,表明白术散可以有效调节血糖、改善胰岛素抵抗,其发挥疗效的途径可能与白术散消渴生津,燥湿利水功效有关。钱宇洁[101]用白术散加牡丹皮、黄连、干姜联合盐酸二甲双胍片治疗31例脾虚型2型糖尿病患者,发现其可以明显降低血糖(空腹血糖及餐后2h血糖),改善胰岛功能(空腹胰岛素、胰岛素抵抗指数),改善中医证候,调节血糖血脂。另有临床研究表明,白术散在脾虚型妊娠期糖尿病治疗过程中,可以有效改善患者的血糖血脂水平,并减少并发症,提高患者临床满意度[102]。以上临床研究均表明,白术散可以有效辅助治疗糖尿病,减少并发症和不良反应的出现。
临床研究表明,白术散可以有效促进儿童生长发育。用药后,发育迟缓儿童患者的胰岛素样生长因子-1(IGF-1)水平、身高(Ht)、生长速度(GV)及身高均值标准差积分(HtSDS)均有明显改善[103]。邓丽华[104]通过临床研究发现白术散可以增加厌食症患者的体质量、促进血红蛋白增长、改善食欲食量且不良反应少。韩娇[105]对比白术散与葡萄糖酸锌治疗儿童气虚厌食症的效果,发现白术散组在增加患儿血锌含量、增加患儿食量等方面优于葡萄糖酸锌对照组,还可以改善患儿神疲倦怠、腹泻等中医证候,且复发率低,无不良反应。
临床上,白术散对慢性胃炎、小儿肠系膜淋巴结炎、儿童特应性皮炎具有良好的治疗效果。舒建波等[106]使用白术散联合西药常规用药治疗31例慢性胃炎患者,治疗后总有效率高于结肠宁对照组。临床研究表明,加减白术散治疗小儿肠系膜淋巴结炎可明显减轻腹痛,改善精神倦怠、大便稀溏等症状,同时还可以改善患儿虚寒体质,达到标本兼治的效果[107]。刘芳榕等[108]基于中医的“整体观念”和“辨证论治”理论,于临床研究发现以白术散为基础方还可以治疗儿童特应性皮炎。
综上,经过大量临床研究和验证,白术散对小儿腹泻、肠易激综合征、小儿轮状病毒性肠炎、糖尿病、小儿生长迟缓、厌食症等疾病治疗均表现出良好的临床效果,同时还可用于治疗慢性胃炎、小儿肠系膜淋巴结炎和儿童特应性皮炎等多种疾病。
刘昌孝院士基于现有的中药质量标准和中药质量评价标准现存问题提出新概念-Q-Marker。中药Q-Marker是中药质量的标态性物质,描述白术散Q-Marker的发现路径,有利于对白术散进行质量控制。本文基于“五原则”对白术散QMarker进行预测,详细研究路径见图2
以白术散的组成药物“人参”“白术”“葛根”“广藿香”“茯苓”“木香”“甘草”为关键词在中药系统药理学分析平台TCMSP(http://tcmspw.com/tcmsp.php)检索,共检索出777个成分,其中人参190个,白术55个,葛根18个,广藿香94个,茯苓34个,木香106个,甘草280个。以口服利用度≥30%、药物相似性≥0.18为标准,筛选得到白术散中有157个活性成分,其中22个属于人参,7个属于白术,4个属于葛根,11个属于广藿香,15个属于茯苓,6个属于木香,92个属于甘草。剔除8个重复成分,得到白术散149个活性成分。
中药复方化学成分复杂,对中药入血成分的研究是解释药物作用机制的关键。因此,对白术散入血成分的研究是其QMarker确定的重要依据。研究者通过质谱技术在给药人参大鼠血清样本中检测到人参皂苷Rg1、Re、Rb1、Rd、Rc、Rb3、Rb2[109]。李媚等[110]建立14批广藿香药材指纹图谱,并基于质量标志物“五原则”和网络药理学分析结果将毛蕊花糖苷和广藿香酮作为广藿香潜在的质量标志物。洪方等[111]利用超高效液相色谱-四极杆飞行时间质谱(ultra performance liquid chromatography-quadrupole time-of-flightmass spectrometry,UHPLC-Q-TOF-MS)技术分析Wistar雌性大鼠给药葛根汤后的血清样本,葛根素、大豆苷和大豆苷元均为其入血成分。能纪娟[112]在给药桂枝茯苓丸的雄性SD大鼠血清样本中分离和鉴定出归属于茯苓的猪苓酸C和去氢土莫酸等化学成分。研究者利用UHPLC-Q-TOF-MS技术分别在给药甘草后的大鼠血清样本和给药香连丸的小鼠血清样本中分离鉴定出甘草苷、甘草酸[113]和木香烃内酯、去氢木香内酯、异二氢木香烃内酯[114]等化学成分。
基于以上文献研究,人参皂苷Rg1、Re、Rb1、Rd、Rc、Rb3、Rb2、葛根素、大豆苷、大豆苷元、猪苓酸C、去氢土莫酸、甘草酸、甘草苷、木香烃内酯、去氢木香内酯、毛蕊花糖苷、广藿香酮可能是白术散的入血成分。
人参为五加科植物人参Panax ginseng C.A.Mey.的干燥根和根茎,具有免疫调节、抗肿瘤、抗氧化应激等药理作用[115]。皂苷类成分是人参的主要活性成分,也是其指标性成分,其特征成分为人参皂苷Rg1、Rb1、Re、Rg3、Rh1[116]
白术为菊科植物白术Atractylodesmacrocephala Koidz.的干燥根茎,其药理作用包括抗肿瘤、抗炎、调节胃肠道、调节免疫系统等[117]。萜类及其内酯类成分是白术的主要化学成分,也是白术挥发油的主要成分。土炒白术后,白术内酯Ⅰ、Ⅱ、Ⅲ含量增加,苍术酮含量减少,其特征成分为白术内酯Ⅰ、Ⅱ、Ⅲ等[118]
葛根为豆科植物野葛Pueraria lobata(Willd.)Ohwi.的干燥根,其药理作用包括改善胰岛素抵抗、保肝、抗肿瘤、抗氧化、神经保护等[119]。黄酮类成份是葛根的主要化学成分,也是其药理作用的物质基础,大豆苷和大豆苷元在豆科植物葛根、甘草中均存在,在葛根中含量较高,故葛根的特征成分为葛根素,大豆苷、大豆苷元[120]
广藿香为唇形科植物广藿香Pogostemon cablin(Blanco)Benth.的干燥地上部分,其药理作用包括抗炎、抗菌、调节胃肠道等。单萜倍半萜是广藿香挥发油的主要组成部分,广藿香的特征成分为百秋李醇、广藿香酮及其藿香黄酮醇等[121]
茯苓为多孔菌科真菌茯苓Poria cocos(Schw.)Wolf的干燥菌核,其药理作用包括抗肿瘤、免疫调节、抗炎、抗氧化等。三萜类和多糖类是其主要的化学成分,茯苓的特征成分为猪苓酸C、去氢土莫酸等三萜酸类成分及茯苓多糖[122]
木香为菊科植物木香Aucklandia lappa Decne.的干燥根,其药理作用包括调节胃肠道、抗炎、抗菌等。木香的特征成分及挥发油成分主要为萜类,如去氢木香内酯、木香烃内酯、3,5-O-二咖啡酰基奎宁酸等[123]
甘草为豆科植物甘草Glycyrrhiza uralensis Fisch.、胀果甘草Glycyrrhiza inflata Bat.或光果甘草Glycyrrhiza glabra L.的干燥根和根茎,其药理作用包括抗菌、抗炎、抗病毒、抗肿瘤、降血糖、调血脂等。黄酮类和三萜类成分是甘草的主要化学成分也是其特征成分,包括甘草苷、甘草素、甘草酸、甘草次酸等[124]
中药的有效性是评价药物整体疗效的前提,也是中药质量控制的核心。因此,有效性是白术散Q-Marker预测分析的核心要素。白术散被誉为“儿科之圣”,古代常用来治疗小儿脾胃虚弱、津虚内热证。现代药理学表明,白术散具有调节肠道微生态、减轻炎症反应、调节血糖、改善胰岛素抵抗、保肝等药理作用,临床上主要用于治疗小儿腹泻、胃炎、糖尿病等疾病。
研究表明[125]人参皂苷Rg1、Re通过改善肠道形态、上调紧密连接蛋白表达、抑制肠道炎症因子表达,发挥调节肠道微生态的药理作用。相关研究表明白术内酯Ⅰ、Ⅲ对TNF-α、IL-1β、IL-6等炎症因子具有明显的抑制作用[126],而白术内酯Ⅱ则通过抑制Nlrp3-ASC-Caspasel活化,达到抑制炎症因子的作用[127],白术内酯Ⅰ、Ⅱ、Ⅲ均可通过减轻胃肠道炎症反应以达到改善肠道微生态的作用。刘培文[128]发现广藿香中的百秋李醇可以抑制NF-κB及Wnt/β-catenin信号转导通路的活化和相关炎性细胞因子的持续高表达,缓解胃黏膜的炎症反应,从而保护胃黏膜,治疗胃炎。现有研究表明肠道炎症的发生与肠道内硫化氢(H2 S)浓度过高有关,高璐[129]发现木香烃内酯和去氢木香内酯具有消耗肠道内H2 S的能力,推测含有这两种成分的中药木香治疗溃疡性结肠炎(ulcerative colitis,UC)的作用机制之一就是抑制病理状态下肠道内过高的H2 S水平。
近年来,人参皂苷的降血糖活性受到广泛关注。大量体内外实验证实,人参皂苷如Rg2、Rg3、Rg5、Rh1等具有降血糖、抗糖尿病及其并发症的作用[130]。葛根中的葛根素、大豆苷、大豆苷元等异黄酮类成分,可以调控晚期糖基化终末产物(advanced glycosylation end products,AGEs)-晚期糖基化终末产物受体(receptor of AGEs,RAGE)等糖尿病的主要信号通路,并抑制乙酰辅酶A羧化酶(acetyl CoA carboxylase,ACC)、蛋白酪氨酸磷酸酶(protein tyrosine phosphatase,PTP)-1B等蛋白的表达,抑制胰岛素抵抗,发挥调节血糖的作用[131-133]
有研究指出[134],人参皂苷Rb1 可显著降低高脂血症大鼠模型的血清中总胆固醇和甘油三酯含量,激活SLC7A11/GPx4信号通路,缓解肝细胞脂肪空泡,从而降低肝组织中的脂质沉积,发挥护肝的药理作用。吴德建等[135]发现大豆苷元可以通过激活SIRT1/AMPK信号通路,增强自噬反应,从而减轻非酒精性脂肪肝大鼠的肝脏损伤。而葛根素主要通过调节肝脏的Dusp9-ASK1信号通路,在非酒精性脂肪肝小鼠模型发挥保肝作用[136]。此外,多项研究表明大豆苷、大豆苷元、葛根素可以显著降低血醇浓度,通过抑制ALDH22活性实现抗酒精作用,从而实现解酒护肝作用[137-138]
综上所述,人参皂苷Rg1、Rb1、Re、Rg3、Rh1、白术内酯Ⅰ、Ⅱ、Ⅲ、葛根素、大豆苷、大豆苷元、百秋李醇、去氢木香内酯、木香烃内酯等成分,可作为白术散Q-Marker的预测参考。
中药复方是中医临床用药的主要形式,其根本目的是减毒增效,而不同的药物配伍会产生不同的作用,从而达到不同的治疗目的,因此白术散的Q-Marker预测要从配伍环境出发[139]。中药复方配伍理论的典型代表是“君臣佐使”,白术散由四君子汤加广藿香、木香、葛根组成。其中,人参为君药,具有补脾益气之功效;辅以白术、茯苓健脾益气,兼以祛湿,使湿祛脾自健;加以葛根以鼓舞胃气止泻,使脾胃生生之气渐复;木香、藿香合用,芳香醒脾、化湿行滞;藿香、葛根合用,“有表则治表,无表则治里”;甘草为使药,具有缓急止痛、调和诸药之功效。全方可起到健脾养胃,益气生津的作用。
白术散由四君子汤加广藿香、木香、葛根组成,吕邵娃等[140]研究发现四君子汤在浸泡2 h、料液比1∶8、提取2次每次40 min的工艺条件下,人参皂苷Rg1、Re、甘草酸等指标成分含量最高,调节肠道免疫活性更好。刘培等[141]采用苯酚-浓硫酸比色法、亚硝酸钠-硝酸铝-氢氧化钠比色法、1%香草醛乙酸-高氯酸比色法分别建立了四君子汤中总多糖、总黄酮、总皂苷的含量测定方法,通过工艺考察表明总黄酮的最佳工艺为料液比1∶8,煎煮3次,每次60 min;总黄酮最佳工艺为料液比1∶10,煎煮1次60 min;总皂苷的最佳工艺为料液比1∶12,煎煮4次每次45 min。唐圆等[142]发现在提取白术散总苷时,在煎煮时间53 min、提取次数2次、料液比1∶13.7(g/mL)条件下,其平均转移率能提升至(0.71±0.01)%。以上工艺研究可为白术散Q-Marker的预测提供参考。
中药复方化学成分复杂,有效成分是复方疗效得以保证的基础,因此成分的可测性是白术散Q-Marker预测分析的必备条件。2020年版《中华人民共和国药典》规定人参、白术、葛根、广藿香、茯苓、木香、甘草的含量测定成分有人参皂苷Rg1、Rb1、Re、葛根素、百秋李醇、木香烃内酯、去氢木香内酯、甘草苷、甘草酸铵。
李菡等[143]通过液相色谱-质谱联用技术(High Performance Liquid Chromatography-Mass Spectrometry,HPLC-MS)建立了白术散标准煎液指纹图谱,标定指纹图谱特征峰10个,分别为大豆苷、大豆苷元、毛蕊花糖苷、异毛蕊花糖苷、人参皂苷Rb1、Rb2、木香烃内酯、去氢木香内酯、白术内酯Ⅱ和茯苓酸A,该方法具有良好的稳定性和重复性。崔业波等[144]采用HPLC法测定不同来源11批人参须中的人参皂苷Re、Rg1、Rb1、Rb2含量,结果显示检测方法合理可行且重复性好。周红艳等[145]建立了同时测定白术内酯Ⅰ、Ⅱ、Ⅲ含量的HPLC方法,该方法能同时测定白术质量控制的主要指标。吴萍等[146]建立了葛根的UPLC指纹图谱,可为白术散中葛根素的测定方法提供参考。张宏武等[147]采用气相色谱法,建立了测定广藿香中百秋李醇和广藿香酮含量的方法,方法稳定可靠。胡益杰等[148]采用HPLC技术建立了木香药材的指纹图谱,以木香烃内酯为参照确立了40个共有峰,该方法可用于同时测定木香烃内酯和去氢木香内酯。陈素娥等[149]建立了茯苓HPLC指纹图谱及多指标成分定量方法,确立去氢土莫酸、猪苓酸C、去氢茯苓酸和松苓新酸为茯苓的指标成分。刘梅清等[150]采用紫外分光光度法测定了甘草总黄酮含量,建立了采用HPLC法测定甘草苷和甘草酸含量的方法并建立了指纹图谱。以上方法可为白术散质量控制提供参考。
综上所述,基于Q-Marker预测分析的“五原则”,人参皂苷Rg1、Rb1、Re、白术内酯Ⅰ、Ⅱ、Ⅲ、葛根素、大豆苷、大豆苷元、百秋李醇、去氢木香内酯、木香烃内酯、甘草苷、甘草酸、去氢土莫酸、猪苓酸C可作为白术散的Q-Marker,具体信息见表2图3
白术散为中医常用的补益剂,具有健脾养胃、益气生津的功效,主要用于治疗脾胃虚弱、津虚内热证,临床常用于治疗小儿腹泻、厌食、消化不良,以及辅助治疗糖尿病、高血脂等。中药复方具有多成分、多靶点的特点,需要建立完整可靠的质量评价体系来控制白术散的整体质量。目前,对白术散的研究多集中在临床应用方面,对其成分含量测定、入血成分及其代谢物、作用机制等方面研究尚不充分,还需进一步深入研究。本文基于质量标志物的“五原则”,对白术散的Q-Marker进行了预测分析,结果表明人参皂苷Rg1、Rb1、Re、白术内酯Ⅰ、Ⅱ、Ⅲ、葛根素、大豆苷、大豆苷元、百秋李醇、去氢木香内酯、木香烃内酯、甘草苷、甘草酸、去氢土莫酸、猪苓酸C可作为白术散的质量标志物,本研究可为基于质量标志物的白术散质量评价体系的构建提供参考依据。
  • 全国重点实验室专项(2023QGZDSYS002)
  • 江西省重点研发项目(20243BCC31010)
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2025年第43卷第12期
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doi: 10.13193/j.issn.1673-7717.2025.12.002
  • 首发时间:2026-04-29
  • 出版时间:2025-12-10
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全国重点实验室专项(2023QGZDSYS002)
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    1.江西中医药大学现代中药制剂教育部重点实验室,江西 南昌 330004
    2.经典名方现代中药创制全国重点实验室,江西 南昌 330004

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臧振中(1979-),男,河南周口人,副教授,硕士研究生导师,博士,研究方向:中药制造新工艺和新装备。E-mail:
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2种不同金属材料的力学参数

Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)

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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