Article(id=1322926267384865554, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1322925862630339452, articleNumber=null, orderNo=null, doi=10.13193/j.issn.1673-7717.2025.07.037, 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=1793339800925, onlineDateStr=2026-10-30, pubDate=1752076800000, pubDateStr=2025-07-10, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1793339800925, onlineIssueDateStr=2026-10-30, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1793339800925, creator=13701087609, updateTime=1793339800925, updator=13701087609, issue=Issue{id=1322925862630339452, tenantId=1146029695717560320, journalId=1255847919539208197, year='2025', volume='43', issue='7', pageStart='1', pageEnd='258', issueExtLink='null', onlineDate='null', pubDate='1752076800000', pubDateStr='2025-07-10', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1793339704424, creator='13701087609', updateTime=1793340532184, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1322929334587105328, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1322925862630339452, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1322929334587105329, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1322925862630339452, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=190, endPage=194, ext={EN=ArticleExt(id=1322926267644912403, articleId=1322926267384865554, tenantId=1146029695717560320, journalId=1255847919539208197, language=EN, title=Quality Control Status and Predictive Analysis of Quality Markers of Duhuo(Angelicae Pubescentis Radix), columnId=1256183361521967297, journalTitle=Chinese Archives of Traditional Chinese Medicine, columnName=Target on National Project, runingTitle=null, highlight=null, articleAbstract=

Duhuo(Angelicae Pubescentis Radix)is a classic wind-dampness eliminating medicine with outstanding efficacy of eliminating wind-dampness and relieving paralysis and pain,which is widely used in the treatment of bone diseases. However,there are many varieties of Duhuo(Angelicae Pubescentis Radix)and its efficacy varies greatly,so the effectiveness of clinical use of the drug cannot be guaranteed. Standardizing the quality of Chinese herbal medicines is the basis for ensuring the safety and effectiveness of the clinical use of Duhuo(Angelicae Pubescentis Radix). In this paper,it reviewed the current status of quality control of Duhuo(Angelicae Pubescentis Radix),pointed out the inadequacy of only using the contents of serpentin and dihydroparsinol angelic acid ester as the quality control standard,and at the same time,combined with the core concept of Quality Marker(Q-Marker),it predicted the Q-Marker from the aspects of phytopharmacology,chemical constituent peculiarities,traditional medicinal properties,the measurability of the chemical constituents,different compounding environments,different harvesting periods and preparation methods and new efficacies. The Q-Marker was used to predict the efficacy of Duhuo(Angelicae Pubescentis Radix). The results revealed that the coumarin-like components,such as serpentin,dihydroeucalyptol angelate,isoeucalyptol,citronellolide,psoralen,eucalyptol and scopoletin,and volatile oils,such as eucalyptol methyl ether,α-myrcene alcohol,2-(diethylaminophenylmethyl)cyclohexyl alcohol,β-hydroxycaryophyllene,angelicin A and angelicin G could be used as the Q-Markers of Duhuo(Angelicae Pubescentis Radix),which provided a reference basis to set up a comprehensive and perfect quality control system for Duhuo(Angelicae Pubescentis Radix).

, authors=Hongyang DONG1, 2, Lianrui WANG1, 2, Yike AN1, 2, Huiyan YANG1, 2, Mingsan MIAO1, 2, authorsList=Hongyang DONG, Lianrui WANG, Yike AN, Huiyan YANG, Mingsan MIAO, authorCompany=null, correspAuthors=Mingsan MIAO, authorNote=null, correspAuthorsNote=null, copyrightStatement=null, 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, fund=null), CN=ArticleExt(id=1322926268034982676, articleId=1322926267384865554, tenantId=1146029695717560320, journalId=1255847919539208197, language=CN, title=独活的质量控制现状及质量标志物(Q-Marker)预测分析, columnId=1256183362172142382, journalTitle=中华中医药学刊, columnName=国家项目点击, runingTitle=null, highlight=null, articleAbstract=

独活是一味经典的祛风湿药,具有突出的祛风除湿,通痹止痛的功效,被广泛应用于骨系疾病的治疗中。但独活品种繁多且药效差异大,临床用药的有效性无法得到保障。规范独活的中药材质量,是保证独活临床用药安全有效的基础。综述了独活质量控制的现状,指出仅以蛇床子素和二氢欧山芹醇当归酸酯含量作为质控标准的不足,同时结合质量标志物(Quality marker,Q-Marker)的核心概念,从植物亲缘学、化学成分特有性、传统药性、化学成分的可测性、不同配伍环境、不同采收期和炮制方法以及新的功效等方面预测独活的Q-Marker。结果发现,香豆素类成分,如蛇床子素、二氢欧山芹醇当归酸酯、异欧前胡素、香柑内酯、补骨脂素、欧前胡素和东莨菪内酯;挥发油类成分,如欧芹酚甲醚、α-没药醇、2-(二乙氨基苯基甲基)环己醇、β-水芹烯、当归醇A、当归醇G等可作为独活的Q-Marker,为建立独活全面、完善的质量控制体系提供了参考依据。

, authors=东红阳1, 2, 王连睿1, 2, 安一珂1, 2, 杨卉妍1, 2, 苗明三1, 2, authorsList=东红阳, 王连睿, 安一珂, 杨卉妍, 苗明三, authorCompany=null, correspAuthors=苗明三, authorNote=

东红阳(1998-),女,河南驻马店人,硕士,研究方向:中药药理学。

, correspAuthorsNote=
苗明三(1965-),男,河南新乡人,教授,博士研究生导师,博士,研究方向:中药药理学。E-mail:。
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2.河南中医药大学豫药全产业链研发河南省协同创新中心,河南 郑州 450046, bio={"content":"

东红阳(1998-),女,河南驻马店人,硕士,研究方向:中药药理学。

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东红阳(1998-),女,河南驻马店人,硕士,研究方向:中药药理学。

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独活的质量控制现状及质量标志物(Q-Marker)预测分析
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东红阳 1, 2 , 王连睿 1, 2 , 安一珂 1, 2 , 杨卉妍 1, 2 , 苗明三 1, 2
中华中医药学刊 | 国家项目点击 2025,43(7): 190-194
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中华中医药学刊 |国家项目点击 2025 , 43 (7) : 190 -194
独活的质量控制现状及质量标志物(Q-Marker)预测分析
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东红阳1, 2, 王连睿1, 2, 安一珂1, 2, 杨卉妍1, 2, 苗明三1, 2
作者信息
  • 1.河南中医药大学,河南 郑州 450046
  • 2.河南中医药大学豫药全产业链研发河南省协同创新中心,河南 郑州 450046
通讯作者:
苗明三(1965-),男,河南新乡人,教授,博士研究生导师,博士,研究方向:中药药理学。E-mail:。
作者简介:

东红阳(1998-),女,河南驻马店人,硕士,研究方向:中药药理学。

Quality Control Status and Predictive Analysis of Quality Markers of Duhuo(Angelicae Pubescentis Radix)
Hongyang DONG1, 2, Lianrui WANG1, 2, Yike AN1, 2, Huiyan YANG1, 2, Mingsan MIAO1, 2
Affiliations
  • 1.Henan University of Chinese Medicine,Zhengzhou 450046,Henan,China
  • 2.Collaborative Innovation Center of Research and Development on The Whole Industry Chain of Yu-Yao,Henan University of Chinese Medicine,Zhengzhou 450046,Henan,China
出版时间: 2025-07-10 doi: 10.13193/j.issn.1673-7717.2025.07.037
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独活是一味经典的祛风湿药,具有突出的祛风除湿,通痹止痛的功效,被广泛应用于骨系疾病的治疗中。但独活品种繁多且药效差异大,临床用药的有效性无法得到保障。规范独活的中药材质量,是保证独活临床用药安全有效的基础。综述了独活质量控制的现状,指出仅以蛇床子素和二氢欧山芹醇当归酸酯含量作为质控标准的不足,同时结合质量标志物(Quality marker,Q-Marker)的核心概念,从植物亲缘学、化学成分特有性、传统药性、化学成分的可测性、不同配伍环境、不同采收期和炮制方法以及新的功效等方面预测独活的Q-Marker。结果发现,香豆素类成分,如蛇床子素、二氢欧山芹醇当归酸酯、异欧前胡素、香柑内酯、补骨脂素、欧前胡素和东莨菪内酯;挥发油类成分,如欧芹酚甲醚、α-没药醇、2-(二乙氨基苯基甲基)环己醇、β-水芹烯、当归醇A、当归醇G等可作为独活的Q-Marker,为建立独活全面、完善的质量控制体系提供了参考依据。

独活  /  质量标志物  /  质量控制

Duhuo(Angelicae Pubescentis Radix)is a classic wind-dampness eliminating medicine with outstanding efficacy of eliminating wind-dampness and relieving paralysis and pain,which is widely used in the treatment of bone diseases. However,there are many varieties of Duhuo(Angelicae Pubescentis Radix)and its efficacy varies greatly,so the effectiveness of clinical use of the drug cannot be guaranteed. Standardizing the quality of Chinese herbal medicines is the basis for ensuring the safety and effectiveness of the clinical use of Duhuo(Angelicae Pubescentis Radix). In this paper,it reviewed the current status of quality control of Duhuo(Angelicae Pubescentis Radix),pointed out the inadequacy of only using the contents of serpentin and dihydroparsinol angelic acid ester as the quality control standard,and at the same time,combined with the core concept of Quality Marker(Q-Marker),it predicted the Q-Marker from the aspects of phytopharmacology,chemical constituent peculiarities,traditional medicinal properties,the measurability of the chemical constituents,different compounding environments,different harvesting periods and preparation methods and new efficacies. The Q-Marker was used to predict the efficacy of Duhuo(Angelicae Pubescentis Radix). The results revealed that the coumarin-like components,such as serpentin,dihydroeucalyptol angelate,isoeucalyptol,citronellolide,psoralen,eucalyptol and scopoletin,and volatile oils,such as eucalyptol methyl ether,α-myrcene alcohol,2-(diethylaminophenylmethyl)cyclohexyl alcohol,β-hydroxycaryophyllene,angelicin A and angelicin G could be used as the Q-Markers of Duhuo(Angelicae Pubescentis Radix),which provided a reference basis to set up a comprehensive and perfect quality control system for Duhuo(Angelicae Pubescentis Radix).

Duhuo(Angelicae Pubescentis Radix)  /  quality markers  /  quality control
东红阳, 王连睿, 安一珂, 杨卉妍, 苗明三. 独活的质量控制现状及质量标志物(Q-Marker)预测分析. 中华中医药学刊, 2025 , 43 (7) : 190 -194 . DOI: 10.13193/j.issn.1673-7717.2025.07.037
Hongyang DONG, Lianrui WANG, Yike AN, Huiyan YANG, Mingsan MIAO. Quality Control Status and Predictive Analysis of Quality Markers of Duhuo(Angelicae Pubescentis Radix)[J]. Chinese Archives of Traditional Chinese Medicine, 2025 , 43 (7) : 190 -194 . DOI: 10.13193/j.issn.1673-7717.2025.07.037
独活为伞形科植物重齿毛当归Angelica pubescens Maxim.f.biserrata Shan et Yuan的干燥根,味辛、苦,性微温,归肾、膀胱经,具有祛风除湿,通痹止痛的功效,常用于治疗风寒湿痹,腰膝疼痛,少阴伏风头痛,风寒挟湿头痛等[1]。独活药用价值极高,其有效成分主要包括香豆素类成分[2],如蛇床子素、二氢欧山芹醇当归酸酯、二氢欧山芹醇乙酸酯、欧前胡素、异欧前胡素、香柑内酯、补骨脂素、欧前胡素和东莨菪内酯等;挥发油类成分[3],如萜品油烯、石竹烯、喇叭醇、α-没药醇、2-(二乙氨基苯基甲基)环己醇、β-水芹烯、当归醇A、当归醇G等;以及胡萝卜苷、阿魏酸、新绿原酸等其他成分。现代药理学研究表明,独活具有显著的抗氧化、抗抑郁以及抗阿尔茨海默病等活性[4]。独活始载于《神农本草经》[5]:“独活。味苦,平。主治风寒所击,金疮止痛,贲豚,痫痓,女子疝瘕。久服轻身,耐老。一名羌活,一名羌青,一名护羌使者。”由此可见,早期独活与羌活均作为独活使用,独活为正名,羌活为别名。后经过长期的演变,独活和羌活分化为两个独立的品种。2020年版《中华人民共和国药典》[1](以下简称《中国药典》)规定独活来源为伞形科植物重齿毛当归Angelica pubescens的干燥根。但当今入药独活依旧面临品种多、药效差异大的局面,在东南亚国家有近70种植物被当作中药独活使用[6],其中伞形科植物重齿毛当归的根品质及效用优于其他植物,也被《中国药典》作为独活正品收载。当今中药独活主产于湖北、重庆、四川、陕西等地,以湖北、重庆交界地带所产为道地。为控制独活的药材质量,保证其临床药效,促进其中药资源的开发和使用,本文通过分析独活的质量控制现状,后结合刘昌孝院士提出的中药质控新理念:中药质量标志物(Quality marker,Q-Marker)理论,预测独活的Q-Marker,以期为建立独活完整的质量控制体系提供依据,最终促进独活的应用及发展。
2020年版《中国药典》第一部记载了独活鉴别检查、含量测定的具体方法,对独活的质量控制以蛇床子素(C15H16 O3)和二氢欧山芹醇当归酸酯(C19 H20O5)的含量为标准,规定采用高效液相色谱法(High performance liquid chromatography,HPLC)测定,独活干燥品中蛇床子素含量不得少于0.50%,二氢欧山芹醇当归酸酯含量不得少于0.080%[5]。但只将这两种化学成分含量作为独活药材质量控制的标准很难体现中药成分的整体性和关联性,无法全面地衡量独活的药材质量。胡奕勤[7]以HPLC法为基础,采用一测多评法,以蛇床子素为内标物,计算与二氢欧山芹醇当归酸酯及异欧前胡素的相对校正因子,从而计算二者含量,并将结果与外标法的测定结果比较,证明一测多评法的准确性,试图为独活质量控制提供新的思路。李绪翠等[8]收集11批独活样品,采用HPLC法建立了独活HPLC指纹图谱,标定了11个共有峰,结果发现不同批次的独活药材化学成分含量存在较大差异,为独活质量控制提供了参考。顿珠次仁等[9]利用超高效液相色谱-四级杆-飞行时间质谱联用(Ultra high performance liquid Chromatography-quadrupole-time of flight/mass spectrometry,UHPLC-Q-TOF/MS)技术从独活中鉴定出34个香豆素类化合物,其中29个为首次报道,为独活成分及其药效物质基础研究提出了新见解。钱沉鱼等[3]利用全二维气相色谱-四极杆飞行时间质谱(Gaschromatography×Gaschromatography-quadrupole-time of flight/mass spectrometry,GC×GC-QTOF/MS)技术,分离鉴定出207种独活挥发油成分,通过半定量分析确定独活挥发油中主要包含酯类、醇类、酚类以及碳氢化合物,为挖掘独活挥发油及独活的质量控制作出了巨大贡献。冯彦梅[10]利用现代色谱和光谱技术对独活中的蛇床子素、二氢欧山芹醇当归酸酯和异欧前胡素进行定量分析,从而达到控制独活质量的目的,为独活的质量控制提供依据。李亮等[11]采用HPLC法同时测定独活中伞形花内酯、花椒毒素、佛手柑内酯、蛇床子素、二氢欧山芹醇当归酸酯5个成分的含量建立了独活可靠的含量测定方法,为独活的质量控制提供参考。张元萍等[12]考察了不同炮制工艺对独活中二氢欧山芹醇、蛇床子素、异欧前胡素和二氢欧山芹醇当归酸酯4种香豆素类成分含量的影响,结果发现不同炮制工艺对独活中香豆素类成分含量产生较大影响。郭晓霞等[13]利用HPLC测定独活饮片中的异虎耳草素、二氢欧山芹醇醋酸酯、蛇床子素和二氢欧山芹醇当归酸酯的含量,为独活的质量控制提供依据。由此可见,随着现代检测手段的不断发展,HPLC法、UHPLC-Q-TOF/MS技术、GC×GC-QTOF/MS等技术被广泛应用于独活化学成分的分离和鉴定中,为独活的质量控制提供了技术支撑。根据当前国内外报道,独活所含化学成分复杂,主要为香豆素类成分[9]和挥发油类成分[2],除此以外还包括有机酸、多烯烃、植物甾醇和糖类等[14]。仅以一种或几种化学成分含量作为独活的质量控制指标不能有效地评判独活的质量,更不能评判其临床疗效。因此,以质量标志物理论为依据,从植物亲缘学、化学成分特有性、传统药性、化学成分的可测性、不同配伍环境、不同采收期和炮制方法以及新功效等方面多角度地对独活的质量标志物进行预测分析,已成为当今控制独活质量,保证其临床作用的有效策略。
独活是伞形科当归属多年生重齿毛当归的干燥根,当归属植物分布广泛,药用资源丰富,目前已经发现约110种植物[15],其中包含代表性药用植物独活[16]、当归[17]、白芷[18]等。当归属植物广泛分布于亚洲,欧洲和北美,当今在中国甘肃、云南、四川、陕西和湖北省广泛种植,在越南被作为药用植物栽培[19]。独活和羌活在《神农本草经》中被载为一物,后在长期的临床应用中演化为两个药材。《中国药典》规定独活中蛇床子素含量不得少于0.50%,二氢欧山芹醇当归酸酯含量不得少于0.080%[5]。而羌活的质量控制标准为挥发油含量不得少于1.4%(mL/g),干燥品中含羌活醇(C2 H22 O5)和异欧前胡素(C6 H14 O4)的总量不得少于0.40%。可见独活和羌活在药效物质基础及发挥作用的有效成分已经被清晰地区分开。现代研究表明,当归属所含化学成分主要包括挥发油[20]、香豆素[21]、呋喃香豆素[22]、苯酞[23]、多糖[24]、苯并呋喃[25]、聚乙炔[26]等,其中挥发油类和香豆素类成分含量较高,独活作为当归属植物其化学成分满足当归属植物的共性,但又存在自己化学成分的特有性。独活主要成分为包含蛇床子素、二氢欧山芹醇当归酸酯在内的香豆素类以及欧芹酚甲醚、α-没药醇、2-(二乙氨基苯基甲基)环己醇和4-羟基-3-甲基苯乙酮在内的挥发油类成分。周璐丽[27]对独活化学成分进行了研究,结果发现独活所含香豆素类化合物中蛇床子素、二氢欧山芹醇当归酸酯含量最高,其次为异欧前胡素、香柑内酯、补骨脂素、欧前胡素和东莨菪内酯等成分,且上述成分为独活发挥抗菌、抗氧化活性的主要物质基础。钱沉鱼等[3]对独活的挥发油类成分进行研究,发现欧芹酚甲醚含量最高(相对含量为30.07%),其具有促分泌、驱虫、抗增殖等药理活性;此外,α-没药醇(3.34%)、2-(二乙氨基苯基甲基)环己醇(2.87%),β-水芹烯(2.68%)和4-羟基-3-甲基苯乙酮(2.23%)等活性物质的相对含量较高,也具有较好的药用价值。因此,基于植物亲缘学及化学成分特有性推测蛇床子素、二氢欧山芹醇当归酸酯、异欧前胡素、香柑内酯、补骨脂素、欧前胡素、东莨菪内酯、α-没药醇、2-(二乙氨基苯基甲基)环己醇、β-水芹烯和4-羟基-3-甲基苯乙酮可作为独活的Q-Marker。
中药的传统功效是古人长期用药治疗疾病的经验总结,是对现代临床用药的指导。而“有效性”也是Q-Marker的核心要素,独活的药效成分是独活关键的质量标志物。2020年版《中国药典》记载独活具有“祛风除湿,通痹止痛”的功效,常用于风寒湿痹,腰膝疼痛,少阴伏风头痛,风寒挟湿头痛的治疗。《滇南本草》[28]对独活的记载有:“表汗,治两胁、面寒疼痛”。可见独活具有很好的祛风湿、除痹痛的功效。现代药理学研究表明,独活具有抗炎、抗氧化和预防阿尔茨海默病的作用[6]。乙军等[29]探究了独活挥发油类成分灌胃对兔膝骨关节炎(Osteoarthritis,OA)的作用机制,结果表明挥发油类成分通过减少膝关节滑液中炎性介质白细胞介素-1(Interleukin-1,IL-1)的分泌、促进转化生长因子-β(Transforming growth factor beta,TGF-β)的分泌,发挥抗炎作用,从而减轻滑膜炎症,缓解软骨细胞的破坏。裴媛等[30]研究了独活香豆素类成分对帕金森病模型大鼠抗氧化功能及兴奋性氨基酸谷氨酸含量的影响,结果表明独活香豆素类成分可通过提高血清中总超氧化物歧化酶(Total-superoxide dismutase,T-SOD)的活性、抑制血清和脑组织脂质过氧化反应,发挥抗氧化作用,以及降低血清和脑组织兴奋性氨基酸含量对抗帕金森病。曹刘丹等[31]探究了独活醇提取物抗骨质疏松的作用,发现补骨脂素、香柑内酯、angelmarin、没药当归烯酮和(11S,16S,9Z)-9,17-octadecadiene-12,14-diyne-1,11,16-triol可显著抑制破骨细胞分化。因此,基于传统功效推测独活中香豆素类和挥发油类成分可作为独活的QMarker。
中药药性是对中药性质、气味的概括,是指中药所具有的与治疗作用有关的性能,包括四气五味、归经、毒性等。中药药性是前人在长期实践中对为数众多药物的各种性质及其医疗作用的了解与认识不断深化,进而加以概括和总结出来的,是中医学理论体系中一个重要组成部分,因此“药性”也是中药质量标志物筛选的依据。独活味辛、苦,性微温。归肾、膀胱经。中医药理论认为辛味作为五味之一,能散、能行、能通、能温、能升、能润、能化[32],苦味中药常具有活血化瘀、清热解毒、理气宽中、祛风除湿等功效[33],与独活祛风除湿,通痹止痛的功效相互应证。辛味药的主要成分为挥发油成分,其次是苷类和生物碱类成分[32],苦味药中多含生物碱、挥发油、黄酮、鞣质等物质[34]。独活属辛温药,化学成分尤以挥发油类成分为主。因此,基于传统药性推测独活中挥发油类成分可作为独活的Q-Marker。
中药药效具有多成分和多靶点的作用特点,明确中药的成分是中药药效物质基础确定基础。目前对中药化学成分的研究手段日益丰富,中药所含化学成分日渐明确。准确测定的化学成分对中药质量标志物的确定具有重要的贡献。李欠等[2]采用质谱成像技术确定了独活根和根皮所含的主要化学成分,并确定了蛇床子素、东莨菪内酯、白花前胡醇、紫花前胡素、佛手酚、川白芷素以及二氢欧山芹醇乙酸酯、二氢欧山芹醇当归酸酯、白当归素和新比克白芷内酯所存在的组织分布。陈颖等[35]比较5批独活样品中东莨菪内酯、二氢欧山芹素、补骨脂素、花椒毒素、香柑内酯、蛇床子素、异欧前胡素和二氢欧山芹醇当归酸酯8种香豆素类含量,发现差异明显。顿珠次仁等[9]以UHPLC-QTOF/MS技术建立裂叶独活中香豆素类化学成分的快速定性分析方法,发现独活中不同类型香豆素具有独特的裂解规律,从独活中共鉴定出34个香豆素类化合物,其中29个为首次报道。张恭孝等[36]用HPLC测定独活饮片中的异虎耳草素、二氢欧山芹醇醋酸酯、蛇床子素、二氢欧山芹醇当归酸酯的含量,试图为独活的质量控制提供依据,证实该成分重复性较好、结果分离度高,可以应用于独活含量测定。贾萌等[37]运用高效液相色谱-二极管阵列检测法(High-performance liquid chromatography-photodiode array,HPLC-PDA)建立15批独活饮片的指纹图谱,测定二氢欧山芹素、当归醇A、当归醇G、二氢欧山芹醇乙酸酯、蛇床子素、二氢欧山芹醇当归酸酯6个成分的含量,结果相似度在0.858~0.986,为独活饮片质量标准的建立提供理论指导。因此,基于化学成分可测性推测独活中蛇床子素、二氢欧山芹醇当归酸酯、二氢欧山芹醇乙酸酯、二氢欧山芹素、东莨菪内酯、白花前胡醇、紫花前胡素、异欧前胡素、佛手酚、川白芷素、白当归素和新比克白芷内酯、补骨脂素、花椒毒素、香柑内酯、异虎耳草素、当归醇A、当归醇G可作为独活的质量标志物。
独活常与其他中药配伍使用,以发挥不同的功效作用,因此从不同的配伍环境出发,找出该环境下发挥药效的组分,是独活质量标志物预测的重要步骤。独活的名方“独活寄生汤”具有祛风湿、止痹痛的功效,在骨科疾病的治疗中广泛应用[38]。陈若冰[39]研究发现异补骨脂素、异欧前胡素、二氢欧山芹醇当归酸酯等多种成分能显著改善炎症反应,治疗慢性关节炎、类风湿性关节炎等疾病。“加味独活寄生合剂”具有养血舒筋,祛风除湿的功效,易南星[40]通过加味独活寄生合剂中的活性成分进行药效验证,发现紫花前胡苷能抑制骨赘形成,改善骨体积,减轻炎症反应和软骨细胞损伤,黄芩素能够减轻软骨损伤,抑制滑膜炎症反应,是其治疗腰肌劳损、骨质增生症的药效基础。“独活桂辛方”常用于腰椎间盘突出症急性期的治疗,起到缓急止痛的作用,方中独活为君药发挥祛风除湿,通络止痛的功效。徐艺珈等[41]研究证实独活中蛇床子素、花椒毒素、欧前胡素、异欧前胡素、补骨脂素五种化合物成分对控制疼痛传导的hNav1.7峰电流值的均呈浓度依赖性抑制关系。因此,基于不同配伍环境中表达组分推测独活中蛇床子素、二氢欧山芹醇当归酸酯、异补骨脂素、异欧前胡素、欧前胡素、紫花前胡苷、黄芩素、花椒毒素可作为独活的质量标志物。
独活的采收和炮制在实际生产中呈现多样化的特点,独活的采收时间主要有春季或秋季两种,独活的炮制方法古代有淫羊藿制、盐制、炒制、焙制、酒制等,现代应用以生品为主。不同采收时间的独活效用成分含量存在差异,不同的炮制工艺对独活中效用成分的保留和损耗也有着不同的影响,根据不同采收期和炮制方法下独活化学成分的含量变化预测独活的质量标志物,对独活的采收和炮制具有规范作用。蒋季明等[42]比较了不同采收期及生长年限独活中蛇床子素和二氢欧山芹醇当归酸酯的含量,证实不同采收期及生长年限的独活蛇床子素和二氢欧山芹醇当归酸酯的含量具有明显差异。张元萍等[12]考察现代不同炮制工艺对独活中4种香豆素类成分含量的影响,发现不同炮制工艺对二氢欧山芹醇、蛇床子素、异欧前胡素和二氢欧山芹醇当归酸酯的含量影响很大。林茂祥等[43]为研究重庆巫山独活最佳采收期,比较了重庆巫山独活不同采收期产量性状及蛇床子素、二氢欧山芹醇当归酸酯含量,结果蛇床子素、二氢欧山芹醇当归酸酯含量与采收期呈现一定关系。因此,基于采收期和炮制方法化学成分含量变化推测蛇床子素、二氢欧山芹醇当归酸酯、二氢欧山芹醇、异欧前胡素可作为独活的质量标志物。
独活常用来治疗风湿痹痛,现代药理学研究表明,独活除具有抗炎、抗氧化以及在骨系疾病中的应用外,目前还在癌症、肝脏、脑等危重疾病的治疗中发挥重要作用。LIU W B等[44]研究发现蛇床子素能够抑制乳腺癌细胞的转移、侵入,促进乳腺癌细胞凋亡。赵邯涛等[45]对独活醇提物的保肝作用进行了研究,发现独活醇提物可通过激活Toll样受体4(Toll-like receptor 4,TLR4)/髓样分化蛋白88(Myeloid differentiationfactor 88,MyD88)/核转录因子κB(Nuclear factor-κB,NF-κB)信号通路以及核因子E2相关因子2(Nuclear factor erythroid-derived 2-like 2,Nrf2)/Kelch样环氧氯丙烷相关蛋白1(Kelch-like ECH-associated protein 1,Keap1)信号通路,减轻炎症反应以及抑制氧化应激从而发挥保肝效果,这些醇提物主要包括蛇床子素、二氢欧山芹醇当归酸酯在内的26个香豆素类成分和5个有机酸类、3个其他类成分。教亚男等[46]探讨了独活香豆素类成分对阿尔茨海默模型小鼠的神经保护作用,结果发现,14.4 mg/kg的独活香豆素能够通过增强中分子量神经丝蛋白表达和减少细胞凋亡减少阿尔茨海默模型小鼠脑内神经性损伤,从而发挥抗阿尔茨海默病的功效。孔李婷等[47]研究发现,独活中蛇床子素、欧前胡素、异欧前胡素3种成分可通过抑制血管平滑肌上的Ca2+通道,减少细胞外Ca2+内流,抑制内皮细胞上NO途径,对大鼠离体胸主动脉发挥舒张作用,且3种成分具有协同增效的作用。因此,基于新的药效用途推测香豆素类成分可作为独活的质量标志物。
独活作为一味古老的中药材,自始便发生与羌活混用的现象,但随着本草考证的细化,现代化学对成分研究的深入,以及明显的药效差异,两者的差异性已使其演化成两种不同的中药材。具体实践中独活品种依旧较为复杂,大约来源于2科种植物,常见的有川独活类型(来源于当归属植物重齿毛当归A biserrata.f.biserrata Shan et Yuan)、香独活类型(来源于当归属毛当归A.pubescens Maxim.)、牛尾独活类型(来源于独活属Heracleum植物)及九眼独活类型(来源于五加科植物Aralia cordata Thunb.)等。1930年《药物出产辨》[48]中载独活:“产湖北兴山县、巴东县,沙市内资丘山为最”。指出正品独活即川独活的道地产区,为中药材独活的质量控制奠定基础。但独活的溯源只是独活质量控制的一小部分,从采收到临床应用经历多个环节,任何一个环节的变化都会对独活药材的质量和药效产生巨大的影响,建立科学、全面的质量控制体系是保证独活临床疗效的基础。
独活具有良好的祛风除湿、通痹止痛的功效,是临床常用的祛风湿药。明确独活的Q-Marker,可规范建立其质控体系,促进独活的开发和应用。2020年版《中国药典》中以蛇床子素和二氢欧山芹醇当归酸酯含量作为其质量控制的依据,但缺乏测定与其疗效和质量相关的成分。本文综述了独活当前的成分研究手段和质量控制现状,并以Q-Marker的理论作指导,从植物亲缘学及化学成分特有性、传统功效、传统药性、化学成分可测性、不同配伍环境中表达组分、不同采收期和炮制方法化学成分含量变化和新的药效用途七个方面进行独活质量标志物的预测分析。为全面建立独活的质量评价体系,保证独活的临床药效提供基础。
最后得出结论,香豆素类成分,如蛇床子素、二氢欧山芹醇当归酸酯、异欧前胡素、香柑内酯、补骨脂素、欧前胡素和东莨菪内酯;挥发油类成分,如欧芹酚甲醚、α-没药醇、2-(二乙氨基苯基甲基)环己醇、β-水芹烯、当归醇A、当归醇G等可作为独活的质量标志物,为独活建立完善的质量控制体系提供参考,为临床用药的有效性和规范性提供保障。未来研究还需进一步对独活所含的化学成分进行分离,明确独活的效用成分,借助网络药理学、分子对接等手段探寻独活发挥药理作用的活性成分,并将其与独活药材的质量评价相关联,建立独活逐步完善的质量评价体系。
  • 国家自然科学基金项目(82274119)
  • 国家中医药管理局岐黄学者项目(国中医药人教函〔2022〕6号)
  • 河南省重大专项(221100310400)
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2025年第43卷第7期
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doi: 10.13193/j.issn.1673-7717.2025.07.037
  • 首发时间:2026-10-30
  • 出版时间:2025-07-10
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基金
国家自然科学基金项目(82274119)
国家中医药管理局岐黄学者项目(国中医药人教函〔2022〕6号)
河南省重大专项(221100310400)
作者信息
    1.河南中医药大学,河南 郑州 450046
    2.河南中医药大学豫药全产业链研发河南省协同创新中心,河南 郑州 450046

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苗明三(1965-),男,河南新乡人,教授,博士研究生导师,博士,研究方向:中药药理学。E-mail:。
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2种不同金属材料的力学参数
科
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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