Article(id=1322926352789287293, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1322926217711726961, articleNumber=null, orderNo=null, doi=10.13193/j.issn.1673-7717.2025.08.030, 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=1793339821287, onlineDateStr=2026-10-30, pubDate=1754755200000, pubDateStr=2025-08-10, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1793339821287, onlineIssueDateStr=2026-10-30, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1793339821287, creator=13701087609, updateTime=1793339821287, updator=13701087609, issue=Issue{id=1322926217711726961, tenantId=1146029695717560320, journalId=1255847919539208197, year='2025', volume='43', issue='8', pageStart='1', pageEnd='258', issueExtLink='null', onlineDate='null', pubDate='1754755200000', pubDateStr='2025-08-10', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1793339789083, creator='13701087609', updateTime=1793340517761, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1322929274071679978, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1322926217711726961, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1322929274071679979, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1322926217711726961, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=149, endPage=158, ext={EN=ArticleExt(id=1322926353040945534, articleId=1322926352789287293, tenantId=1146029695717560320, journalId=1255847919539208197, language=EN, title=Research Progress on Shashen Maidong Decoction(沙参麦冬汤)for Pulmonary Diseases and Its Quality Marker Prediction Analysis, columnId=1256183361521967297, journalTitle=Chinese Archives of Traditional Chinese Medicine, columnName=Target on National Project, runingTitle=null, highlight=null, articleAbstract=

Shashen Maidong Decoction(沙参麦冬汤)is a classic formula created by WU Jutong,a famous medical expert in the Qing Dynasty.Modern research has shown that Shashen Maidong Decoction has good anti-inflammatory,antioxidant,antitumour and immune-regulating effects,and is able to treat a wide range of lung diseases such as chronic bronchitis,pneumonia,chronic obstructive pulmonary disease,pulmonary fibrosis and lung cancer.In this paper,it reviewed the chemical composition,pharmacological effects and research progress of Shashen Maidong Decoction in the treatment of pulmonary diseases.Meanwhile,based on the five principles of quality marker(Q-marker),it revealed that 17 components such as Bergapten,Ruscogenin,Cucurbitacin B,Rutin,Trigonelline and Liquiritin could be used as the quality markers of Shashen Maidong Decoction,but the subsequent experiments were needed to further verify the authenticity,so as to provide more basis for the quality evaluation of Shashen Maidong Decoction.

, authors=Hongjiang ZHU1, Lijian PANG2, Tianjiao WANG2, Ningzi ZANG2, Li YANG2, Mei WANG1, Yihe QIU1, Qi SI1, Xiaodong LYU1, authorsList=Hongjiang ZHU, Lijian PANG, Tianjiao WANG, Ningzi ZANG, Li YANG, Mei WANG, Yihe QIU, Qi SI, Xiaodong LYU, authorCompany=null, correspAuthors=Xiaodong LYU, 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=1322926355935015301, articleId=1322926352789287293, tenantId=1146029695717560320, journalId=1255847919539208197, language=CN, title=沙参麦冬汤治疗肺系疾病研究进展及其质量标志物(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=

沙参麦冬汤是清代医学名家吴鞠通创造的经典验方,现代研究表明,沙参麦冬汤具有良好的抗炎、抗氧化、抗肿瘤和调节免疫作用,能够治疗慢性支气管炎、肺炎、慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)、肺纤维化和肺癌等多种肺系疾病。回顾沙参麦冬汤的化学成分、药理作用和治疗肺系疾病研究进展。同时基于质量标志物(Q-Marker)五大原则,揭示出佛手柑内酯、鲁斯可皂苷元、葫芦素B、芦丁、葫芦巴碱、甘草苷等17个成分可作为沙参麦冬汤质量标志物,但需要后续实验进一步验证真伪,从而为沙参麦冬汤质量评价提供更多依据。

, authors=祝宏江1, 庞立健2, 王天娇2, 臧凝子2, 杨丽2, 王梅1, 邱奕赫1, 司琦1, 吕晓东1, authorsList=祝宏江, 庞立健, 王天娇, 臧凝子, 杨丽, 王梅, 邱奕赫, 司琦, 吕晓东, authorCompany=null, correspAuthors=吕晓东, authorNote=

祝宏江(2001-),男(满族),辽宁瓦房店人,硕士在读,研究方向:中医肺系疾病基础与临床。

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吕晓东(1966-),女,辽宁海城人,主任中医师、教授,博士研究生导师,博士,研究方向:中医肺系疾病基础和临床。Email:。
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祝宏江(2001-),男(满族),辽宁瓦房店人,硕士在读,研究方向:中医肺系疾病基础与临床。

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祝宏江(2001-),男(满族),辽宁瓦房店人,硕士在读,研究方向:中医肺系疾病基础与临床。

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成分名称化学式CAS号来源
豆甾醇C29H48O83-48-7北沙参、桑叶、麦冬
槲皮素C15H10O7117-39-5北沙参、桑叶、甘草
异槲皮苷C21H20O12482-35-9北沙参、桑叶、甘草
芦丁C27H30O16153-18-4北沙参、桑叶、甘草
东莨菪内酯C10H8O492-61-5北沙参、桑叶
茵芋苷C15H16O893-39-0北沙参、桑叶
β-谷甾醇C29H52O83-46-5北沙参、桑叶
尿苷C9H12N2O658-96-8北沙参、麦冬
亚油酸甲酯C19H34O2112-63-0天花粉、甘草
β-胡萝卜素C40H567235-40-7白扁豆、桑叶
IsoramanoneC21H32O44644-99-9甘草、桑叶
伞形花内酯C9H6O393-35-6甘草、桑叶
紫云英苷C21H20O11480-10-4甘草、桑叶
山柰酚C15H10O6520-18-3甘草、桑叶
), ArticleFig(id=1322926361773486538, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322926352789287293, language=CN, label=表1, caption=

沙参麦冬汤各中药共有化学成分

, figureFileSmall=null, figureFileBig=null, tableContent=
成分名称化学式CAS号来源
豆甾醇C29H48O83-48-7北沙参、桑叶、麦冬
槲皮素C15H10O7117-39-5北沙参、桑叶、甘草
异槲皮苷C21H20O12482-35-9北沙参、桑叶、甘草
芦丁C27H30O16153-18-4北沙参、桑叶、甘草
东莨菪内酯C10H8O492-61-5北沙参、桑叶
茵芋苷C15H16O893-39-0北沙参、桑叶
β-谷甾醇C29H52O83-46-5北沙参、桑叶
尿苷C9H12N2O658-96-8北沙参、麦冬
亚油酸甲酯C19H34O2112-63-0天花粉、甘草
β-胡萝卜素C40H567235-40-7白扁豆、桑叶
IsoramanoneC21H32O44644-99-9甘草、桑叶
伞形花内酯C9H6O393-35-6甘草、桑叶
紫云英苷C21H20O11480-10-4甘草、桑叶
山柰酚C15H10O6520-18-3甘草、桑叶
), ArticleFig(id=1322926361840595403, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322926352789287293, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
中药来源化学成分特有成分参考文献
北沙参伞形科植物珊瑚菜Glehnia littoralis Fr. Schmidtex Miq.的干燥根。香豆素类、聚炔类、木脂素类、单萜糖苷类、酚酸类、挥发油类以及多糖类等。佛手柑内酯、花椒毒素、补骨脂素和法卡林二醇[61]
麦冬 百合科植物麦冬Ophiopogon j aponicas(L.f)Ker-Gawl.的干燥块根。甾体皂苷类、高异黄酮类、多糖类、有机酸类、挥发油类和微量元素类等。鲁斯可皂苷元、甲基麦冬黄酮A、甲基麦冬黄酮B、甲基麦冬黄烷酮A、甲基麦冬黄烷酮B和麦冬皂苷D[61-62]
玉竹 百合科植物玉竹Polygonatum odoratum(Mill)Druce的干燥根茎。多糖类、高异黄酮类、皂苷类和糖蛋白类等。玉竹多糖(葡萄糖)[63]
天花粉葫芦科植物梧楼Trichosanthes kirilowii Maxim.或双边梧楼Trichosanthes rosthornii Harms的干燥根。三萜类、蛋白质类、皂苷类、黄酮类、多糖类、氨基酸类和无机元素类等。葫芦素B和葫芦素E[17,67]
桑叶 桑科植物桑Morus alba L.的干燥叶。黄酮类、有机酸类、生物碱类、多糖类和蛋白质类等。芦丁、绿原酸、异槲皮苷和1-DNJ[64]
白扁豆豆科植物扁豆Dolichos lablab L.的干燥成熟种子。三萜类、生物碱类、黄酮类、脂类、多糖类、蛋白质类、维生素类和微量元素类等竹节参皂苷IVa和葫芦巴碱[22,65]
甘草 豆科植物甘草Glycyrrhiza uralensis Fisch.、胀果甘草Glycyrrhiza inf lata Bat.或光果甘草Glycyrrhizaglabra L.的干燥根和根茎。黄酮类、三萜类、苯丙素类、核苷、碱基类及多糖类等甘草苷、异甘草苷、甘草素、异甘草素、甘草酸和甘草次酸[66]
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沙参麦冬汤特有性成分

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中药来源化学成分特有成分参考文献
北沙参伞形科植物珊瑚菜Glehnia littoralis Fr. Schmidtex Miq.的干燥根。香豆素类、聚炔类、木脂素类、单萜糖苷类、酚酸类、挥发油类以及多糖类等。佛手柑内酯、花椒毒素、补骨脂素和法卡林二醇[61]
麦冬 百合科植物麦冬Ophiopogon j aponicas(L.f)Ker-Gawl.的干燥块根。甾体皂苷类、高异黄酮类、多糖类、有机酸类、挥发油类和微量元素类等。鲁斯可皂苷元、甲基麦冬黄酮A、甲基麦冬黄酮B、甲基麦冬黄烷酮A、甲基麦冬黄烷酮B和麦冬皂苷D[61-62]
玉竹 百合科植物玉竹Polygonatum odoratum(Mill)Druce的干燥根茎。多糖类、高异黄酮类、皂苷类和糖蛋白类等。玉竹多糖(葡萄糖)[63]
天花粉葫芦科植物梧楼Trichosanthes kirilowii Maxim.或双边梧楼Trichosanthes rosthornii Harms的干燥根。三萜类、蛋白质类、皂苷类、黄酮类、多糖类、氨基酸类和无机元素类等。葫芦素B和葫芦素E[17,67]
桑叶 桑科植物桑Morus alba L.的干燥叶。黄酮类、有机酸类、生物碱类、多糖类和蛋白质类等。芦丁、绿原酸、异槲皮苷和1-DNJ[64]
白扁豆豆科植物扁豆Dolichos lablab L.的干燥成熟种子。三萜类、生物碱类、黄酮类、脂类、多糖类、蛋白质类、维生素类和微量元素类等竹节参皂苷IVa和葫芦巴碱[22,65]
甘草 豆科植物甘草Glycyrrhiza uralensis Fisch.、胀果甘草Glycyrrhiza inf lata Bat.或光果甘草Glycyrrhizaglabra L.的干燥根和根茎。黄酮类、三萜类、苯丙素类、核苷、碱基类及多糖类等甘草苷、异甘草苷、甘草素、异甘草素、甘草酸和甘草次酸[66]
), ArticleFig(id=1322926361995784653, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322926352789287293, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
序号成分名称化学式CAS 来源
1佛手柑内酯C12H8O4484-20-8北沙参
2花椒毒素C12H8O4298-81-7北沙参
3补骨脂素C11H6O366-97-7北沙参
4鲁斯可皂苷元C27H42O4472-11-7麦冬
5甲基麦冬黄酮AC19H16O674805-90-6麦冬
6甲基麦冬黄烷酮AC19H18O674805-92-8麦冬
7甲基麦冬黄烷酮BC19H20O574805-91-7麦冬
8麦冬皂苷DC44H70O16945619-74-9麦冬
9葫芦素BC32H46O86199-67-3天花粉
10葫芦素EC32H44O818444-66-1天花粉
11芦丁C27H30O16153-18-4桑叶
12异槲皮苷C21H20O12482-35-9桑叶
13绿原酸C16H18O9327-97-9桑叶
14葫芦巴碱C7H7NO2535-83-1白扁豆
15甘草苷C21H22O9551-15-5甘草
16甘草素C15H12O4578-86-9甘草
17甘草酸C42H62O161405-86-3甘草
), ArticleFig(id=1322926362062893518, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322926352789287293, language=CN, label=表3, caption=

沙参麦冬汤质量标志物(Q-marker)

, figureFileSmall=null, figureFileBig=null, tableContent=
序号成分名称化学式CAS 来源
1佛手柑内酯C12H8O4484-20-8北沙参
2花椒毒素C12H8O4298-81-7北沙参
3补骨脂素C11H6O366-97-7北沙参
4鲁斯可皂苷元C27H42O4472-11-7麦冬
5甲基麦冬黄酮AC19H16O674805-90-6麦冬
6甲基麦冬黄烷酮AC19H18O674805-92-8麦冬
7甲基麦冬黄烷酮BC19H20O574805-91-7麦冬
8麦冬皂苷DC44H70O16945619-74-9麦冬
9葫芦素BC32H46O86199-67-3天花粉
10葫芦素EC32H44O818444-66-1天花粉
11芦丁C27H30O16153-18-4桑叶
12异槲皮苷C21H20O12482-35-9桑叶
13绿原酸C16H18O9327-97-9桑叶
14葫芦巴碱C7H7NO2535-83-1白扁豆
15甘草苷C21H22O9551-15-5甘草
16甘草素C15H12O4578-86-9甘草
17甘草酸C42H62O161405-86-3甘草
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沙参麦冬汤治疗肺系疾病研究进展及其质量标志物(Q-marker)预测分析
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祝宏江 1 , 庞立健 2 , 王天娇 2 , 臧凝子 2 , 杨丽 2 , 王梅 1 , 邱奕赫 1 , 司琦 1 , 吕晓东 1
中华中医药学刊 | 国家项目点击 2025,43(8): 149-158
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沙参麦冬汤治疗肺系疾病研究进展及其质量标志物(Q-marker)预测分析
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祝宏江(2001-),男(满族),辽宁瓦房店人,硕士在读,研究方向:中医肺系疾病基础与临床。

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祝宏江(2001-),男(满族),辽宁瓦房店人,硕士在读,研究方向:中医肺系疾病基础与临床。

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祝宏江1, 庞立健2, 王天娇2, 臧凝子2, 杨丽2, 王梅1, 邱奕赫1, 司琦1, 吕晓东1
作者信息
  • 1.辽宁中医药大学,辽宁 沈阳 110847
  • 2.辽宁中医药大学附属医院,辽宁 沈阳 110032
通讯作者:
吕晓东(1966-),女,辽宁海城人,主任中医师、教授,博士研究生导师,博士,研究方向:中医肺系疾病基础和临床。Email:。
作者简介:

祝宏江(2001-),男(满族),辽宁瓦房店人,硕士在读,研究方向:中医肺系疾病基础与临床。

Research Progress on Shashen Maidong Decoction(沙参麦冬汤)for Pulmonary Diseases and Its Quality Marker Prediction Analysis
Hongjiang ZHU1, Lijian PANG2, Tianjiao WANG2, Ningzi ZANG2, Li YANG2, Mei WANG1, Yihe QIU1, Qi SI1, Xiaodong LYU1
Affiliations
  • 1.Liaoning University of Traditional Chinese Medicine,Shenyang 110847,Liaoning,China
  • 2.Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110032,Liaoning,China
出版时间: 2025-08-10 doi: 10.13193/j.issn.1673-7717.2025.08.030
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沙参麦冬汤是清代医学名家吴鞠通创造的经典验方,现代研究表明,沙参麦冬汤具有良好的抗炎、抗氧化、抗肿瘤和调节免疫作用,能够治疗慢性支气管炎、肺炎、慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)、肺纤维化和肺癌等多种肺系疾病。回顾沙参麦冬汤的化学成分、药理作用和治疗肺系疾病研究进展。同时基于质量标志物(Q-Marker)五大原则,揭示出佛手柑内酯、鲁斯可皂苷元、葫芦素B、芦丁、葫芦巴碱、甘草苷等17个成分可作为沙参麦冬汤质量标志物,但需要后续实验进一步验证真伪,从而为沙参麦冬汤质量评价提供更多依据。

沙参麦冬汤  /  化学成分  /  药理作用  /  临床应用  /  质量标志物

Shashen Maidong Decoction(沙参麦冬汤)is a classic formula created by WU Jutong,a famous medical expert in the Qing Dynasty.Modern research has shown that Shashen Maidong Decoction has good anti-inflammatory,antioxidant,antitumour and immune-regulating effects,and is able to treat a wide range of lung diseases such as chronic bronchitis,pneumonia,chronic obstructive pulmonary disease,pulmonary fibrosis and lung cancer.In this paper,it reviewed the chemical composition,pharmacological effects and research progress of Shashen Maidong Decoction in the treatment of pulmonary diseases.Meanwhile,based on the five principles of quality marker(Q-marker),it revealed that 17 components such as Bergapten,Ruscogenin,Cucurbitacin B,Rutin,Trigonelline and Liquiritin could be used as the quality markers of Shashen Maidong Decoction,but the subsequent experiments were needed to further verify the authenticity,so as to provide more basis for the quality evaluation of Shashen Maidong Decoction.

Shashen Maidong Decoction(沙参麦冬汤)  /  chemical component  /  pharmacological effect  /  clinical application  /  quality marker
祝宏江, 庞立健, 王天娇, 臧凝子, 杨丽, 王梅, 邱奕赫, 司琦, 吕晓东. 沙参麦冬汤治疗肺系疾病研究进展及其质量标志物(Q-marker)预测分析. 中华中医药学刊, 2025 , 43 (8) : 149 -158 . DOI: 10.13193/j.issn.1673-7717.2025.08.030
Hongjiang ZHU, Lijian PANG, Tianjiao WANG, Ningzi ZANG, Li YANG, Mei WANG, Yihe QIU, Qi SI, Xiaodong LYU. Research Progress on Shashen Maidong Decoction(沙参麦冬汤)for Pulmonary Diseases and Its Quality Marker Prediction Analysis[J]. Chinese Archives of Traditional Chinese Medicine, 2025 , 43 (8) : 149 -158 . DOI: 10.13193/j.issn.1673-7717.2025.08.030
沙参麦冬汤是《温病条辨》中的经典验方,吴鞠通指出“燥伤肺胃阴分,或热或咳者,沙参麦冬汤主之”,可见早在清朝时期前人就已经认识到沙参麦冬汤可有效治疗肺系疾病。原方由北沙参、麦冬、玉竹、天花粉、白扁豆、桑叶和甘草七味中药组成,可治肺胃津亏之证,具有清养肺胃,润燥生津之功。研究表明[1],沙参麦冬汤具有良好的抗炎、抗氧化、抗肿瘤以及调节免疫的作用,因此在临床实践中,可以被广泛用于治疗慢性支气管炎、肺炎、慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)、肺纤维化和肺癌等肺系相关疾病。
质量标志物(quality marker,Q-Marker)是近年兴起的评价或预测中药及中药复方质量标准的最新概念,最早由刘昌孝院士提出,根据Q-marker定义和基本要求,对于沙参麦冬汤的研究应从“质量传递与溯源”“成分特有性”“成分有效性”“复方配伍环境”和“成分可测性”5个方面切入[2]。当前国内外对于沙参麦冬汤化学成分的研究尚少,对其质量标志物的研究亦不充足,本文旨在阐明沙参麦冬汤化学成分、药理作用和治疗肺系疾病研究进展,并预测分析沙参麦冬汤质量标志物。
沙参麦冬汤是由7味中药组成的经典名方,单味中药化学成分种类繁多,沙参麦冬汤多味中药相互配伍后,不同成分发生相关化学反应后产生的新物质亦是复杂多样。现代学者对其单味中药化学成分研究较多,对复方化学成分研究较局限。笔者将从单味中药化学成分和复方化学成分两个方面进行分述。
北沙参是沙参麦冬汤的君药,具有养阴清肺、祛痰止咳之功。北沙参的化学成分包括香豆素类、木脂素类、聚炔类、单萜糖苷类、酚酸类、挥发油类和多糖类等。李师仰团队[3]采用超高效液相色谱-四极杆/静电场轨道阱高分辨质谱(ultrahigh performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry,UHPLC-QExactive Orbitrap HRMS)技术测定16批次北沙参中补骨脂素、佛手柑内酯、花椒毒素、欧前胡素、绿原酸和隐绿原酸等12种化学成分含量,结果显示佛手柑内酯含量较高,而隐绿原酸和花椒毒素含量相对较少。张晴等[4]采用高效液相色谱(high performance liquid chromatography,HPLC)法测定出8个种源北沙参的9种香豆素含量,包括东莨菪苷、秦皮乙素、花椒毒酚、补骨脂素和花椒毒素等成分,为培育高质量北沙参品种提供有价值的参考依据。王辉明团队[5]运用气相-质谱联用(gas chromatography mass spectrometry,GC-MS)技术对3个不同产地的北沙参挥发油成分进行分析,结果揭示镰叶芹醇是北沙参挥发油相对含量最高的共有化合物。
麦冬是沙参麦冬汤的君药,具有滋阴润肺、益胃生津之功,与北沙参相合可甘寒养阴、清热润燥。麦冬化学成分包括皂苷类、黄酮类、多糖类、挥发油类和微量元素类等。祁梅等[6]采用高效液相色谱-蒸发光散射检测器(evaporative light-scattering detector,ELSD)分别对浙麦冬和川麦冬化学成分麦冬皂苷B、麦冬皂苷D、麦冬皂苷D´、甲基麦冬二氢高异黄酮A和甲基麦冬二氢高异黄酮B的含量进行测定,结果表明浙麦冬较川麦冬质量更优。何佳团队[7]采用HPLC法对4-香豆酸、N-反式-P-香豆酰基去甲辛弗林、麦冬酰胺、甲基麦冬黄烷酮A和甲基麦冬黄烷酮B等7种成分进行测定以评估浙麦冬道地性和等级。王菲等[8]应用HPLC-二极管阵列检测器(diode array detector,DAD)-ELSD-MSn多检测器串联技术筛选出麦冬11种甾体皂苷和13种高异黄酮类差异性成分,包括麦冬二氢高异黄酮A、麦冬二氢高异黄酮E、甲基麦冬二氢高异黄酮A、甲基麦冬二氢高异黄酮B、麦冬皂苷C、麦冬皂苷D和麦冬皂苷D´等,研究发现不同干燥方法对川麦冬中甾体皂苷和高异黄酮有明显影响。
玉竹是沙参麦冬汤的臣药,具有养阴润燥、生津止渴的功效。玉竹的活性成分主要为高异黄酮类、多糖类、皂苷类和糖蛋白类等。隋振宇等[9]采用UHPLC-Q-Orbitrap与多种数据解析鉴定出玉竹37种化学成分,包括9种生物碱类(如异鸟苷)、8种黄酮类(如紫云英苷)、4种氨基酸类(如谷氨酸)、3种糖苷类(如乳糖)、2种木脂素类(如五味子醇乙)、1种萜类(即马鞭草苷)、1种有机酸类(即亮氨酸)和9种其他类成分(如甘露醇)。谢菁琛等[10]运用超高效液相色谱-飞行时间质谱(ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry,UHPLC-Q-TOF-MS)结合代谢组学分析玉竹成分差异性,结果显示异油酸、L-苯丙氨酸、黄肉楠碱影响程度排名前三。毕博团队[11]应用GCMS鉴定分析玉竹不同部位挥发油化学成分,指认出丹皮酚是大玉竹挥发油的特有成分,六甲基环三硅氧烷是大玉竹、圆叶玉竹和吉林1号3个品系玉竹根茎及果实挥发油的共有成分。张颖等[12-13]学者运用薄层色谱(thin layer chromatography,TLC)法对玉竹中4种高异黄烷酮进行二次层析,经UPLC验证高异黄烷酮Ⅲ及Ⅳ含量是高异黄烷酮Ⅰ及Ⅴ的3~5倍,这为玉竹质量控制提供依据。
天花粉是沙参麦冬汤的臣药,具有清热泻火、生津止渴、消肿排脓的功效,与玉竹相合可加强君药养阴生津、清热润燥之功。天花粉主要有效成分为氨基酸类、蛋白质类、皂苷类和多糖类等。龚道锋等[14]运用HPLC法测定天花粉中15种氨基酸含量,测定指标包含瓜氨酸、门冬氨酸、苯丙氨酸、赖氨酸和谷氨酸等。陆柳君等[15]对天花粉甲醇提取物乙酸乙酯部位进行分离纯化,鉴定出1种脑苷脂(即大豆脑苷Ⅰ)、2种甾体糖苷[如(24ξ)-24-乙基-胆甾-3-O-β-D-葡萄糖苷]、1种脂肪酸甘油酯(即亚油酸甘油酯)、1种木脂素(即Ligballinol)和4种长链脂肪酸(如亚油酸)。叶淼团队[16]在天花粉乙酸乙酯部位分离得到4种葫芦素类三萜化合物(即葫芦素B、葫芦素D、葫芦素R和雪胆素甲),实验首次分离出葫芦素F型三萜化合物(如雪胆素甲)。徐放等[17]采用HPLC技术测定天花粉中葫芦素B和葫芦素E含量,为钴60-γ射线辐照后的天花粉质量评价提供依据。
桑叶是沙参麦冬汤的佐药,具有疏散风热、清肺润燥的功效。桑叶的主要活性成分为黄酮类、生物碱类、多糖类和蛋白质类等。刘梦文等[18]以桑叶中含量最高的绿原酸为内参物,利用HPLC技术和一测多评法(quantitative analysis of multicomponents by single marker,QAMS)对新绿原酸、绿原酸、隐绿原酸、芦丁、异槲皮苷、紫云英苷、异绿原酸A、异绿原酸B和异绿原酸C等桑叶成分含量进行测定,为桑叶质量控制提供参考。禹鹏鑫等[19]建立UHPLC-DAD指纹图谱,测定没食子酸甲酯、隐绿原酸、芦丁、异槲皮苷、山奈酚-3-O-芸香糖苷和紫云英苷6种关键成分含量,以评估22批次桑叶样品的品质。田海英团队[20]发现蒸制、盐炙和蜜炙桑叶与鲜品、干品桑叶相比,芦丁、槲皮素-3-O-葡萄糖苷和没食子酸含量均不同程度降低,而槲皮素含量不同程度升高。陆城宇等[21]使用超高效液相色谱-三重四极杆质谱(ultra high performance liquid chromatography-triple quadrupole mass spectrometry,UHPLCTQD)技术测定不同产地桑叶样品氨基酸(如苯丙氨酸等)、核苷(如胞苷等)及生物碱(即1-脱氧野尻霉素(1-deoxynojirimycin,DNJ))等成分含量,结果表明湖北与江西产区的1-DNJ等9种成分含量较高。
白扁豆是沙参麦冬汤的佐药,具有补脾止泻、消暑化湿、和中解毒的功效,与桑叶相合可助脾胃运化。白扁豆的化学成分主要含有三萜类、黄酮类、脂类、多糖类、蛋白质类、维生素类和微量元素类等。刘虹等[22]采用UHPLC-Q-TOF-MS和UPLC-ELSD技术分析白扁豆配方颗粒化学成分为Lablaboside E、Lablaboside D、Lablaboside F、Lablaboside B、Copteroside G、Caryocaroside-Ⅱ11和竹节参皂苷IVa等,并测定出竹节参皂苷IVa质量分数。韩君[23]利用UHPLC-Q-Exactive Orbitrap MS技术对白扁豆总皂苷化学成分进行分析,鉴定出CaryocarosideⅡ-11、Azukisaponin VI、Chikusetsusaponin V、Bonushenricoside B、Chikusetsusaponin IVa等18种白扁豆皂苷成分,为进一步阐明白扁豆生物活性成分提供参考。张晓雪[24]团队采用GC-MS技术分析鉴定出白扁豆7种挥发性成分,包括α-芳樟醇、5-甲基-2,2´-亚甲基二呋喃、棕榈酸甲酯、亚油酸甲酯和2-甲基二十烷等,其中α-芳樟醇是白扁豆主要的芳香物质。
甘草是沙参麦冬汤的使药,具有益气补中、润肺止咳、调和药性等功效。甘草的化学成分包括黄酮类、三萜类、苯丙素类、核苷类、碱基类及多糖类等。常冠华团队[25]从甘草地上部分醇提取物中分离得到13种化合物,包括4种二氢黄酮类(如柚皮素)、1种二氢茋类(即α,α′-二氢-5,4′-二羟基-3-乙酰氧基-2-异戊烯基茋)、1种黄酮醇类(即6-异戊烯基槲皮素)、4种黄酮类(如槲皮素-3,3′-二甲醚等)、1种异黄酮类(即刺芒柄花素)和2种脂肪酸类(如邻苯二甲酸二丁酯等)。张志等[26]采用UHPLC-Q-Exactive Orbitrap MS法检测甘草地上部分醇提样品水溶性、脂溶性部位,结果显示水溶性样品中维采宁Ⅲ、芦丁、异槲皮苷、维采宁Ⅱ、紫云英苷、异夏佛塔苷和夏佛塔苷峰面积较高,脂溶性样品中维采宁Ⅲ、紫云英苷、芒柄花苷、黄芩苷、槲皮素、刺芒柄花素和大豆素峰面积较高。吴晓云等[27]运用多波长HPLC-DAD法同时测定美白类化妆品中甘草苷、甘草查尔酮A、甘草查尔酮B、异甘草苷、甘草素、异甘草素和光甘草定等8种甘草成分含量。贾梦楠等[28]通过HPLC-Q-TOF-MS技术标定出甘草10个共有峰,并指认出芹糖甘草苷、芹糖异甘草苷、甘草苷、异甘草苷和甘草酸5种成分。
沙参麦冬汤由北沙参、麦冬、玉竹、天花粉、白扁豆、桑叶和甘草7味中药组成,具有清养肺胃、润燥生津之功。沙参麦冬汤众多化学成分相互协调作用于疾病靶点,进而产生药理作用,其化学成分主要为多糖类、蛋白质类、黄酮类和皂苷类等。吴茵等[29]采用UHPLC-MSMS同时测定复方中芦丁、补骨脂素、花椒毒素、佛手苷内酯、麦冬皂苷D、甲基麦冬二氢高异黄酮A、甲基麦冬二氢高异黄酮B、甘草苷和甘草酸铵等9种成分含量。陈千等[30]分离鉴定出沙参麦冬颗粒正丁醇部位的10种化合物,其中1种环二肽类(即丙氨酸-脯氨酸)、1种苯酚类(即间苯二酚)、1种酚醇类(即对羟基苯乙醇)、4种核苷类(即腺嘌呤、2’-脱氧腺苷、腺苷、次黄嘌呤)和2种氨基酸类(即酪氨酸、L-色氨酸),此外还分离出1种单环倍半萜类(即icariside B1)。国内外对沙参麦冬汤化学成分研究尚少,多数学者结合网络药理学对沙参麦冬汤治疗肺癌机制进行研究,发现沙参麦冬汤活性成分包括槲皮素、β-胡萝卜素、柚皮素、光甘草素、花生四烯酸、芒柄花黄素、光甘草定、山柰酚、豆甾醇、芦丁、异槲皮苷、东莨菪内酯、2-戊基呋喃、β-谷甾醇、2-庚酮、亚油酸、棕榈酸、葡糖醛酸、葫芦巴碱、花生酸和油酸等[31-32]。
沙参麦冬汤是经典的润燥方剂,现代诸多医家对其药理作用开展大量研究,现代研究认为其在抗炎、抗氧化、抗肿瘤和调节免疫等方面均具有积极作用。笔者将从上述4个方面对沙参麦冬汤药理作用进行论述。
炎症是具有血管的活体组织对各种损伤因子刺激做出以防御反应为主的基本病理过程,是发生于多种疾病的共同机制,炎症的产生多和炎症因子密切相关。周燕萍[33]表明,沙参麦冬汤通过降低血浆白细胞介素(interleukin,IL)-6、肿瘤坏死因子(tumor necrosis factor,TNF)-α和转化生长因子β1(transforming growth factor-β1,TGF-β1)等炎症因子水平以减轻肺泡炎症,阻止肺纤维化发展。IL-1、IL-6、TNF-α是机体重要的炎症因子,IL-1诱导IL-6合成,促进局部炎症反应。顾克辉等[34]运用沙参麦冬汤联合常规西药治疗慢性支气管炎发现,其可以降低IL-1、IL-6、TNF-α等炎症因子水平,且联合治疗IL-6、TNF-α水平低于单纯传统西药治疗的炎症因子水平。此外,可溶性尿激酶型纤溶酶原激活剂受体(soluble urokinase-type plasminogen activator receptor,suPAR)是与感染关联的炎症因子,可溶性髓系细胞触发受体-1(soluble triggering receptor expressed on myeloid cell-1,sTREM-1)的血清表达水平与疾病的严重程度及炎症反应成正比,且IL-10可通过抑制IL-6、TNF-α表达以减轻炎症。研究表明[35],沙参麦冬汤联合常规西药治疗肺炎,患者suPAR和sTREM-1的表达水平低于单纯西药治疗组的水平,而IL-10表达水平却高于单纯西药治疗组水平。
氧化与抗氧化平衡紊乱是导致肺系疾病发生的重要机制,因此抗氧化治疗对于减轻慢性肺损伤、延缓疾病进展及抑制肺功能衰退十分重要。在氧化应激中,超氧化物歧化酶(superoxide dismutase,SOD)、谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)作为活性氧(reactive oxygen species,ROS)的生成底物被迅速消耗,且生成的大分子物质丙二醛(malondialdehyde,MDA)会造成细胞损伤。李静等[36]发现,沙参麦冬汤能够提高慢性支气管炎模型大鼠血清中SOD、过氧化氢酶(catalase,CAT)、GSH-Px活性,这表明沙参麦冬汤能够改善大鼠氧化与抗氧化平衡失调状态,可以清除机体自由基,增强大鼠组织抗氧化酶活性,以减轻氧化应激损伤。多数肺癌患者需要接受放疗、化疗等治疗,顺铂治疗是化疗的一线药物,但它带来的副作用和不良反应是巨大的,沙参麦冬汤在改善顺铂化疗所致的肾损伤方面具有优势,动物实验发现顺铂联合沙参麦冬汤治疗Lewis肺癌模型肾损伤小鼠相较于单纯顺铂治疗组,小鼠肾脏组织中SOD、GSH-Px表达量上升,而MDA表达量下降,这提示沙参麦冬汤可能通过抑制氧化应激改善肾脏功能,保护肾脏[37]。
恶性肿瘤是当今世界危害公众生命健康的重大疾病之一,其患者的生存率和生活质量面临巨大挑战,而中医药辅助现代疗法治疗恶性肿瘤能够提高患者生存率和生活质量,沙参麦冬汤也是近年的研究热点。高启龙等[38]发现,沙参麦冬汤能够抑制苯并芘对磷脂酰肌醇3-激酶(phosphatidylinositol 3-kinase,PI3K)/蛋白激酶B(threonine protein kinase,AKT)/哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)信号通路的激活作用,逆转苯并芘对人肺上皮Beas-2B细胞自噬抑制作用,延长人肺上皮Beas-2B细胞恶性转化进展,进而在细胞恶性转化初期发挥沙参麦冬汤抗肿瘤功效。王莹等[39]认为肺癌细胞对化疗药物产生耐药性影响恶性肿瘤治疗效果,若化疗联用沙参麦冬汤可提高临床疗效,该团队发现沙参麦冬汤含药血清能抑制人非小细胞肺腺癌A549细胞增殖生长并能提高上皮-间充质转化(epithelial-mesenchymal transition,EMT)相关蛋白E-cadherin表达水平,降低Snail表达水平,且沙参麦冬汤含药血清与顺铂联用效果更加显著,提示沙参麦冬汤含药血清与顺铂联用的抗肿瘤机制可能与抑制肿瘤细胞发生EMT有关。
免疫机制是人体不可或缺的防御机制,免疫系统时刻抵抗各种病原体入侵,沙参麦冬汤在辅助免疫系统和提高免疫力方面具有相当优势。石磊等[40]发现,沙参麦冬汤联合常规化疗药物紫杉醇-顺铂治疗肺癌能够明显提高CD+3 T淋巴细胞比例、CD+4 T淋巴细胞比例和CD+4/CD+8 T淋巴细胞比值,且上述指标水平显著高于紫杉醇-顺铂组,同时肺癌0~Ⅰ期出现轻度白细胞减少的患者比例显著高于紫杉醇-顺铂组,而Ⅱ~Ⅳ期出现中、重度白细胞减少的患者比例显著低于紫杉醇-顺铂组,这表明紫杉醇联合顺铂化疗基础上加用沙参麦冬汤具有改善患者免疫功能和降低白细胞减少等不良反应的作用。动物实验发现,长期大负荷耐力训练可导致小鼠免疫功能降低,沙参麦冬汤通过提高运动小鼠血清免疫球蛋白(immunoglobulin,Ig)A、IgG和IgM含量以增强B淋巴细胞免疫功能,同时可能通过抵抗长时间大负荷训练引起的机体免疫器官损伤和提高胸腺指数以提高运动小鼠外周血CD+4 T淋巴细胞百分比、CD+4/CD+8 T淋巴细胞比值,进而增强T淋巴细胞免疫功能,上述结果提示沙参麦冬汤能够提升大强度耐力训练小鼠免疫力[41]。
沙参麦冬汤在肺系疾病领域的研究一直以来都是热点,笔者整理近10年文献发现,出现频率较高的疾病包括慢性支气管炎、肺炎、慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)、肺纤维化和肺癌等。笔者将对上述5种肺系疾病研究进展进行分述。
慢性支气管炎是临床常见的肺系疾病之一,临床表现为咳嗽、咳痰、阵发胸闷和喘息等,其发病特征主要为起病缓、病情反复、病程迁延。中医将其归属为“咳嗽”“喘证”的范畴。徐玫颖[42]研究认为加减沙参麦冬汤治疗慢性支气管炎相较于传统西药盐酸氨溴索治疗可以显著缩短慢性支气管炎患者咳嗽、咳痰和喘息等临床症状改善时间,提高临床疗效。季梅等[43]对11篇文献中的1169例慢性支气管炎患者进行荟萃分析,结果表明沙参麦冬汤单独应用或联合西医疗法应用可提高慢性支气管炎患者的临床疗效,减少症状控制时间和住院时间,这提示单用或加用沙参麦冬汤治疗相较于单纯西医常规治疗更有效、更安全。
大量临床文献表明沙参麦冬汤广泛用于治疗放射性肺炎和支原体肺炎,可以有效改善二者临床表现。放射性肺炎是肿瘤患者放疗过程中,正常肺组织受到反复辐射所致的炎性损伤,中医认为“火热伤阴”是其基本病机,可用沙参麦冬汤养阴润肺。中医将其归属为“咳嗽”“喘证”的范畴。研究表明[44],沙参麦冬汤联合放疗治疗恶性肿瘤相较于单纯放疗,放射性肺炎的发病率明显降低,患者的生活质量和稳定性明显提高。支原体肺炎是高发于儿童和青少年间的一种非典型肺炎,临床表现为低热、头痛、刺激性镇咳、咽痛和胸痛等,中医将其归属于“肺炎喘嗽”“咳嗽”等范畴。吕康福[45]认为相比于单纯阿奇霉素静脉滴注治疗,沙参麦冬汤联合阿奇霉素治疗支原体肺炎可显著改善咳嗽、发热、肺部湿啰音等临床表现,提高临床疗效。
COPD是一种持续存在慢性呼吸系统症状和气流受限的可预防的难治性疾病。中医认为其病机为肺气胀满,不能敛降。中医将其归属于“咳嗽”“肺胀”“痰饮”的范畴。温笑薇等[46]通过数据挖掘173例COPD患者用药规律发现,COPD缓解期肺阴亏虚证的主要方剂是沙参麦冬汤,可用之益气养阴,润肺平喘。牛明华[47]研究发现噻托溴铵吸入粉雾剂联合沙参麦冬汤治疗肺阴虚型COPD相较于对照组单用噻托溴铵吸入粉雾剂治疗,联合治疗的一秒用力呼气容积(forced expiratory volume in one second,FEV1)、用力肺活量(forced vital capacity,FVC)和FEV1/FVC水平均高于对照组,6 min步行距离明显长于对照组,咳嗽、痰量、痰液性质、呼吸困难和啰音等积分明显低于对照组,这提示沙参麦冬汤能够改善患者临床表现,提高肺功能,增强运动耐力,减少急性加重次数。
肺纤维化是一种不可逆的慢性肺部疾病,其特点是成纤维细胞大量增殖聚集肺泡、肺间质内细胞外基质累积过量。肺阴亏虚,气滞血瘀是肺纤维化的重要病机。中医将其归属为“肺痹”“肺痿”的范畴。动物实验[48]表明,沙参麦冬汤组肺纤维化小鼠存活率较好,肺组织羟脯氨酸、胶原纤维减少量最佳,结果提示沙参麦冬汤能够提高肺组织弹性纤维含量且对肺组织具有保护作用。吕晓东教授认为,特发性肺纤维化属本虚标实之证,涉及痰、热、瘀、阴虚、气虚和肺络虚等病机,徐嘉通过挖掘吕晓东教授门诊治疗特发性肺纤维化用药规律发现,吕晓东教授常运用沙参麦冬汤、补阳还五汤和止嗽散等方剂治疗特发性肺纤维化,以补虚化痰止咳通络为基本原则,辨证论治,以达到最佳疗效[49]。
肺癌是全球发病率和病死率最高的恶性肿瘤,其症状包括发热、咳嗽、咯血、胸闷气短和胸痛等。气阴两虚、痰瘀热毒互结是肺癌的关键病机。中医认为肺癌归属为“肺积”“积聚”的范畴。笔者查阅文献发现沙参麦冬汤广泛用于肺癌防治领域,且取得良好疗效。张东等[50]运用隐结构结合关联规则研究肺癌中晚期106首方剂用药规律发现,沙参麦冬汤出现频率最高,高达99次,通过以方测证认为该方可益气养阴,化痰止咳,用于治疗气阴两虚型肺癌。郑鑫泽等[51]对14篇文献中的1116例样本进行meta分析认为,沙参麦冬汤辅助化疗治疗非小细胞肺癌在提高疾病控制率、提升卡氏评分、改善免疫功能和减小不良反应上存在明显优势,这表明沙参麦冬汤能有效协同化疗治疗非小细胞肺癌,可明显改善患者生活质量。
此外,沙参麦冬汤也可用于治疗新冠病毒感染和咳嗽变异型哮喘。新冠病毒感染是曾造成全球大流行的一类呼吸系统传染病,郑晓婷等[52]对气阴两虚型新冠病毒感染恢复期患者予以沙参麦冬汤干预后发现,中医证候积分、肺CT和圣乔治呼吸问卷评分等方面均优于常规治疗组。研究表明[53],运用加减沙参麦冬汤联合孟鲁司特钠治疗咳嗽变异型哮喘,可显著改善患者症状、呼气峰流量变异率、IL-6及TNF-α等炎症因子水平。
中药质量标志物的概念是现代中医药领域的一大创新概念,经过近10年的发展和丰满已经趋近成熟,其被广泛用于中药或复方质量标准评估中。根据质量标志物的概念和Qmarker五大原则,建立沙参麦冬汤Q-marker研究路径如下,见插页ⅩLⅨ图1。
通过TCMSP数据库(https://old.tcmsp-e.com/tcmsp.php)分别检索“北沙参”“麦冬”“玉竹”“天花粉”“白扁豆”“桑叶”“甘草”,结果显示北沙参有35个化学成分,玉竹有62个化学成分,天花粉有15个化学成分,白扁豆有14个化学成分,桑叶有269个化学成分,甘草有280个化学成分,共计675个化学成分。以药物口服生物利用度(oral bioavailability,OB)≥30%和类药性(drug likeliss,DL)≥0.18为条件筛选出北沙参活性成分8个,玉竹活性成分8个,天花粉活性成分2个,白扁豆活性成分1个,桑叶活性成分29个,甘草活性成分92个,共计140个活性成分。
TCMSP数据库并未涉及中药麦冬活性成分,使用BATMAN-TCM数据库(http://bionet.ncpsb.org.cn/batman-tcm/index.php),分别以“BEI SHA SHEN”“MAI DONG”“YU ZHU”“TIAN HUA FEN”“BAI BIAN DOU”“SANG YE”“GAN CAO”为关键词,设置条件Score cutoff≥20和Target Analyses中Pvalue<0.05,经系统自动去除不存在结构的化学成分后,得到北沙参17个活性成分,麦冬22个活性成分,玉竹5个活性成分,天花粉55个活性成分,白扁豆4个活性成分,桑叶73个活性成分,甘草125个活性成分,共计301个活性成分。
对上述成分进行合并去重,获得北沙参22个活性成分,麦冬22个活性成分,玉竹13个活性成分,天花粉57个活性成分,白扁豆5个活性成分,桑叶89个活性成分,甘草200个活性成分,共计408个活性成分。运用EVeen(http://www.ehbio.com/test/venn)对涉及成分进行交集处理,获得北沙参-麦冬共有成分1个,北沙参-桑叶共有成分6个,北沙参-麦冬-桑叶共有成分1个,北沙参-甘草共有成分3个,桑叶-白扁豆共有成分1个,桑叶-甘草共有成分7个,天花粉-甘草共有成分1个,合并去重后共计14个共有成分,见表1。
沙参麦冬汤是由7味中药组成的经典润燥方剂,其化学成分复杂丰富,但成分吸收入血并作用于相应疾病靶点后,才可能产生对应功效。当前沙参麦冬汤药代动力学研究尚少,国内外报道沙参麦冬汤多组入血成分的研究十分有限。因此,笔者将从药对或单味中药入血成分进行论述。吴茵等[54]运用UHPLC-MSMS测定出大鼠灌胃沙参麦冬汤后血浆中甘草苷、花椒毒素和麦冬甲基黄烷酮A达峰时间分别为0.42、0.59、0.83 h;消除半衰期分别为3.61、6.93、3.51 h,这提示沙参麦冬汤灌胃后甘草苷、花椒毒素和麦冬甲基黄烷酮A等3种成分入血后被快速吸收。王双[55]采用UPLC-Q-TOF-MS测定大鼠血浆中北沙参-麦冬药对花椒毒素、佛手柑内酯、异茴芹内酯、欧前胡素、补骨脂素、麦冬皂苷D、甲基麦冬黄烷酮A、甲基麦冬黄烷酮B和甲基麦冬高异黄酮A等成分含量变化。有学者运用UPLC-TQ-MS测定10种桑叶黄酮类及生物碱类成分提取物灌胃大鼠后的血药浓度,模型组大鼠体内新绿原酸、隐绿原酸、槲皮素、山柰酚和芦丁等成分最大血药浓度降低,绿原酸、紫云英苷和异槲皮苷等成分最大血药浓度升高[56]。另一项动物实验以芍药甘草汤大孔树脂90%乙醇洗脱部位灌胃小鼠,由小鼠血清鉴定出甘草苷、异甘草苷、甘草素、甘草查尔酮B和甘草酸等10种原型成分[57]。为保证本项研究完整性,笔者查阅文献发现麦冬中鲁斯可皂苷元[58,63]、白扁豆中葫芦巴碱[59,65]、天花粉中葫芦素B和葫芦素E[60]等成分均可入血。综上所述,虽然沙参麦冬汤仅有3种主要入血成分,但上述入血成分亦可作为沙参麦冬汤Q-marker候选物。
成分特有性是单味中药质量控制的重要标准,按照《中华人民共和国药典》2020版确定各单味中药特有成分,并根据文献资料[17,22,61-67]对沙参麦冬汤特有性成分进行补充分析,见表2。
评价沙参麦冬汤成分有效性也是预测其质量标志物的便捷途径。根据国内外相关文献,沙参麦冬汤的研究热点主要围绕疾病和临床,对其化学成分研究十分有限,笔者将围绕抗炎、抗氧化、抗肿瘤和调节免疫4个方面对沙参麦冬汤有效成分相关Q-marker进行预测分析。
佛手柑内酯和花椒毒素作为北沙参的特征性成分,其具有抗炎活性。5-甲氧基补骨脂素(即佛手柑内酯)在10μmol/L浓度下能抑制支气管上皮细胞IL-8表达,该成分是治疗囊性纤维化肺部炎症的潜在药物[68]。另有研究发现在脂多糖(lipopolysaccharide,LPS)诱导的RAW264.7巨噬细胞中,花椒毒素通过抑制真核细胞转录因子κB(nuclear transcription factor-κB,NF-κB)、激活蛋白-1(activator protein-1,AP-1)和Janus激酶(Janus kinase)/信号转导及转录激活蛋白(signal transducer and activator of transcription,STAT)信号通路,减少NO、前列腺素E2(prostaglandin E2,PGE2)、TNF-α和IL-6等因子产生以发挥抗炎作用[69]。詹杉杉[70]运用鲁斯可皂苷元治疗卵清蛋白诱导的哮喘模型小鼠,结果提示小鼠气道阻力和肺泡灌洗液炎症细胞下降,气道及血管周围炎症细胞浸润减少,肺部氧化应激和凋亡均改善。桑叶中的槲皮素和异槲皮素是有效的嗜酸性炎症抑制剂,ROGERIO A P等[71]发现二者均能降低哮喘模型小鼠支气管肺泡灌洗液、血液和肺实质嗜酸性粒细胞计数,但仅有异槲皮素治疗的小鼠血液中性粒细胞计数和肺匀浆IL-5水平较低。甘草是各类方剂配伍的常用中药,甘草的抗炎活性物质为三萜皂苷类、黄酮类及多糖类,其中甘草黄酮类化合物甘草素、甘草苷和甘草查尔酮A等成分通过抑制细胞外信号相关激酶(extracellular signal-related ki-nases,ERK)/丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)通路、减少TNFα和IL-1βmRNA等炎症因子表达和抑制诱导型一氧化氮合成酶(inducible nitric oxide synthase,iNOS)及环氧合酶2(cyclooxygenase-2,COX-2)基因和蛋白水平表达等发挥抗炎作用[72]。
甲基麦冬黄烷酮A和甲基麦冬黄烷酮B是中药麦冬的两种高异黄酮类化合物,均具有抗氧化活性。赵晶等[73]发现,运用甲基麦冬黄烷酮A预处理PC12细胞,其可抑制缺氧复氧损伤后的PC12细胞SOD和CAT活性降低,同时抑制MDA水平升高。另有研究表明,甲基麦冬黄烷酮B能够减轻过氧化氢(hydrogen peroxide,H2 O2)诱导人脐静脉内皮细胞(human umbilical vein endothelial cells,HUVECs)凋亡,降低MDA和活性氧(reactive oxygen species,ROS)水平,增强SOD活性,这提示甲基麦冬黄烷酮B具有良好的抗氧化活性[74]。麦冬皂苷D是一种有效的抗氧化中药单体。徐玲文等[75]报道,相较于LPS组,麦冬皂苷D-LPS组Beas-2B细胞的ROS水平、MDA浓度和髓过氧化物酶(myeloperoxidase,MPO)活性降低,SOD及超氧化物歧化酶(total antioxidative capacity,T-AOC)活性升高,这提示麦冬皂苷D预处理可拮抗LPS介导Beas-2B细胞氧化应激。桑叶活性成分芦丁和绿原酸也是临床报道较多的抗氧化剂。BAI L等[76]发现芦丁可显著降低肺纤维化模型大鼠肺组织MDA含量,提高肺组织GSH含量、SOD活性、血清总抗氧化能力,降低肺组织NO 含量。LARKI-HARCHEGANI A等[77]表明绿原酸可能通过提高百草枯暴露大鼠SOD、CAT和GSH-Px等抗氧化酶活性和阻止炎症细胞浸润,提高肺组织抗氧化能力,阻止炎症扩散和百草枯诱导产生的肺纤维化。
李桂民等[31]运用网络药理学探讨沙参麦冬汤治疗肺癌的机制发现,其主要活性成分是槲皮素、豆甾醇、β-胡萝卜素、山柰酚、β-谷甾醇和柚皮素。研究发现[78],豆甾醇通过调节PI3K/AKT信号通路和线粒体活性氧生成诱导肿瘤细胞凋亡,且调节细胞周期蛋白和细胞周期蛋白依赖性激酶以发挥抗增殖活性。佛手柑内酯和补骨脂素是北沙参潜在的抗肿瘤活性成分。CHIANG SR等[79]报道,佛手柑内酯可能激活肿瘤抗原p53介导的级联反应,显著降低人非小细胞肺癌(non-small cell lung cancer,NSCLC)A549和NCI-H460细胞生存能力,触发G1阻滞和细胞凋亡。刘生元等[80]认为,补骨脂素可能抑制PI3K/AKT信号通路激活,进而对抗NSCLC A549细胞增殖及迁移。葫芦素B和葫芦素E是天花粉抗肿瘤的主要活性成分。ZENG Z等[81]表明,葫芦素B能抑制STAT3激活,导致NSCLC铁下垂,从而减缓NSCLC细胞生长速度。JING SY等[82]报道,葫芦素E干扰表皮生长因子受体(epidermal growth factior receptor,EGFR)/丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)信号通路,从而拮抗NSCLC A549细胞增殖。葫芦巴碱是白扁豆中存在的具有抗癌活性的一种生物碱。FOUZDER C等[83]发现,葫芦巴碱通过抑制EGFR信号通路阻断核因子E2相关因子2(nuclear factor erythroid 2-related factor 2,Nrf2)激活及其核易位发挥抗癌活性,与顺铂/依托泊苷联用可协同抗癌,提高NSCLC患者生存率。
玉竹多糖是玉竹关键的活性成分之一,其可能通过调节肠道菌群,保护肠道屏障,抑制M1巨噬细胞,进而显著改善LPS诱导炎性损伤小鼠的免疫炎症和肺损伤[84]。此外,赵守彰等[85]发现,玉竹醇提取物B可能通过调节免疫代谢减少结直肠癌模型小鼠肿瘤细胞数目及异常增生以发挥抗肿瘤活性。朱俊山等[86]发现,葫芦素B能明显抑制小鼠淋巴细胞增殖、活化和干扰素(intereron,IFN)-γ表达,诱导小鼠淋巴细胞凋亡,这可能与葫芦素B潜在的免疫调节作用有关。秦元华等[87]表明,鸦胆子联合补骨脂素合剂治疗卡氏肺孢子虫肺炎大鼠,CD+4 T淋巴细胞、CD+8 T淋巴细胞和TNF-α等指标水平均升高,大鼠受损的肺组织病变减轻或修复,体重明显回升,肺组织包囊数减少,这提示该合剂可增强免疫功能以抑制卡氏肺孢子虫。袁江浪等[88]发现绿原酸能够抑制人外周血T淋巴细胞体外增殖,并通过下调ROS水平、抑制Th1因子表达和促进Th2分化以调节免疫功能。RENDA G等[89]认为,三萜类化合物甘草酸和甘草次酸主要通过抑制NF-κB和MAPK信号通路并调节与抗炎作用相关的不同机制以改善免疫系统。
此外,北沙参香豆素类还可抗病毒、抗肿瘤、镇痛平喘等[3-4]。麦冬高异黄酮类和皂苷类还具有抗炎、抗肿瘤、抗疲劳和清除自由基等功效[6,73]。玉竹多糖和高异黄酮类还可抗病毒、抗肿瘤及抗衰老等[10,13]。桑叶黄酮类和有机酸类还具有抗病毒、抗肿瘤、抗菌及抑制血小板聚集等功效[20,64]。甘草黄酮类还可抗病毒、抗肿瘤、抗菌、抗衰老、镇痛和调节免疫等[26],甘草三萜类还可抗炎、抗病毒、抗肿瘤及抗氧化等[89]。葫芦巴碱是白扁豆抗感染、抗菌、镇痛等活性的物质基础[22]。天花粉中葫芦素不仅可抗肿瘤和调节免疫,还具有抗炎等活性[67]。因此沙参麦冬汤各成分功效并不是单一的,而是相互协同发挥药效。
复方配伍环境也是影响复方质量标准的重要条件,这是由于复方单味中药相互配伍可能影响复方某一成分含量,因此基于复方配伍环境对沙参麦冬汤质量标志物进行预测是必不可少的环节。沙参麦冬汤方解如下,见插页ⅩLⅨ图2。
中药配伍会影响沙参麦冬汤成分内环境。王双[55]研究北沙参-麦冬药对药物动力学,对灌胃大鼠血浆成分含量进行测定发现,北沙参和麦冬单次配伍后能够提高佛手柑内酯、异茴芹内酯、补骨脂素、欧前胡素、麦冬皂苷D和甲基麦冬高异黄酮A的生物利用度,影响佛手柑内酯、异茴芹内酯和补骨脂素的体内过程,减缓甲基麦冬黄烷酮A和甲基麦冬黄烷酮B吸收。另有研究认为北沙参和麦冬配伍后,能够降低花椒毒酚、补骨脂素、佛手柑内酯等成分含量,升高花椒毒素和异欧前胡素等成分含量;同时升高麦冬皂苷D、甲基麦冬高异黄酮A、甲基麦冬黄烷酮A和甲基麦冬黄烷酮B等成分含量[90]。黄庆勇等[91]运用HPLC同时测定栝楼桂枝汤中9种成分含量,结果显示天花粉与桂枝汤合用后,将减少甘草苷、甘草素、甘草酸3种成分含量,但亦有报道天花粉与甘草配伍有助于甘草酸溶出[92]。中药炮制也会影响药物成分含量,进而改变复方配伍。桑叶通过炮制能够增加绿原酸、芦丁、紫云英苷和异槲皮苷含量,且蜜烘桑叶相较于其他炮制方法含量变化最大[93]。此外,外界环境变化也可能改变中药成分含量,造成疗效不佳和成分失活。60 Co-γ辐照可对中药材灭菌,当天花粉暴露于辐照剂量10k Gy的60 Co-γ辐照中,葫芦素B和葫芦素E含量显著降低[17]。小粒咖啡生豆葫芦巴碱含量随温度上升而增加,随降雨量增加而减少[94],这为葫芦巴碱作为白扁豆Q-marker候选物提供参考。
按照《中华人民共和国药典》[63]2020版之规定,对麦冬、玉竹、桑叶和甘草有效成分进行测定,需要以鲁斯可皂苷元、玉竹多糖(以葡萄糖为主)、芦丁、甘草苷和甘草酸为质量控制指标。《中华人民共和国药典》2020版中尚未涉及北沙参、天花粉和白扁豆质量评价的指标成分。为深入研究沙参麦冬汤成分,前述吴茵等[29]采用UHPLC-MS MS测定其有效成分含量,包括芦丁、补骨脂素、花椒毒素、佛手苷内酯、麦冬皂苷D、甲基麦冬二氢高异黄酮A、甲基麦冬二氢高异黄酮B、甘草酸铵和甘草苷共计9种成分。有学者运用同法测定14批麦冬和16批湖北麦冬成分含量,筛选出甲基麦冬高黄酮A、甲基麦冬黄烷酮A、山麦冬皂苷B、甲基麦冬黄烷酮B、甲基麦冬高黄酮B等8个差异标志物[95]。吕振国等[96]建立中药桑叶UPLC指纹图谱,测定16批桑叶新绿原酸、绿原酸、隐绿原酸、芦丁、异槲皮苷和紫云英苷等8种成分含量。此外,葫芦素B、葫芦素E、葫芦巴碱、甘草苷、甘草酸和甘草素等成分含量亦可检测[97-98]。
建立指纹图谱能够更直观地分析不同化学成分差异。陈薛静等[99]建立沙参麦冬汤物质基准特征图谱,测定出15批沙参麦冬汤的甘草苷含量和转移率,将甘草苷作为参照峰,标定出沙参麦冬汤特征图谱中20个共有峰,且指认出甘草苷、甘草酸铵色谱峰。颜红等[100]对15批沙参麦冬汤HPLC指纹图谱进行分析,标定出沙参麦冬汤指纹图谱26个共有峰,明确1个共有峰来自除甘草外其他药材,1个共有峰来自桑叶、北沙参及玉竹,1个特有峰来自白扁豆,4个特有峰来自桑叶,1个共有峰来自北沙参、天花粉及玉竹,1个共有峰来自除天花粉及甘草外其他药材,3个共有峰来自桑叶及甘草,11个特有峰来自甘草,3个共有峰来自所有药材;并指认出芦丁、甘草苷及甘草酸铵的3个峰。
沙参麦冬汤是由清代医学名家吴鞠通创造的经典验方,在历史长河中,为治疗各类肺系疾病做出巨大贡献。沙参麦冬汤组方严谨科学,后世医家在众多临床疾病中验证其有效性和安全性。虽然现代学者对其单味中药化学成分的研究开展众多,但国内外对其整体组方化学成分的检测和分析十分有限,当前对沙参麦冬汤的研究主要还是围绕疾病和临床。笔者正是在此种条件下论述了沙参麦冬汤化学成分、药理作用、治疗肺系疾病的研究进展,并对其质量标志物预测分析,旨在为沙参麦冬汤质量控制提供理论依据。
经讨论,佛手柑内酯、鲁斯可皂苷元、葫芦素B、芦丁、葫芦巴碱、甘草苷等17个成分与沙参麦冬汤功效关联密切,可测性高,专属性强,可作为沙参麦冬汤的质量标志物,见图3、表3。且玉竹多糖也是沙参麦冬汤发挥药效的活性成分,也可作为其质量控制的参照物。但上述成分仍需后期实验验证其真伪,从而为沙参麦冬汤质量评价提供更多依据。
  • 国家自然科学基金面上项目(82274440)
  • 国家自然科学基金青年科学基金项目(82004294)
  • 辽宁省科技厅创新能力提升联合基金项目(2022-NLTS-13-3)
  • 吕晓东辽宁省名中医传承工作室建设项目(辽中医药函〔2021〕1号)
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2025年第43卷第8期
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doi: 10.13193/j.issn.1673-7717.2025.08.030
  • 首发时间:2026-10-30
  • 出版时间:2025-08-10
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国家自然科学基金面上项目(82274440)
国家自然科学基金青年科学基金项目(82004294)
辽宁省科技厅创新能力提升联合基金项目(2022-NLTS-13-3)
吕晓东辽宁省名中医传承工作室建设项目(辽中医药函〔2021〕1号)
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    1.辽宁中医药大学,辽宁 沈阳 110847
    2.辽宁中医药大学附属医院,辽宁 沈阳 110032

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吕晓东(1966-),女,辽宁海城人,主任中医师、教授,博士研究生导师,博士,研究方向:中医肺系疾病基础和临床。Email:。
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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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