Article(id=1322912243930771609, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1322912162913596032, articleNumber=null, orderNo=null, doi=10.13193/j.issn.1673-7717.2025.01.023, 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=1793336457474, onlineDateStr=2026-10-30, pubDate=1736438400000, pubDateStr=2025-01-10, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1793336457474, onlineIssueDateStr=2026-10-30, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1793336457473, creator=13701087609, updateTime=1793336457473, updator=13701087609, issue=Issue{id=1322912162913596032, tenantId=1146029695717560320, journalId=1255847919539208197, year='2025', volume='43', issue='1', pageStart='1', pageEnd='258', issueExtLink='null', onlineDate='null', pubDate='1736438400000', pubDateStr='2025-01-10', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1793336438157, creator='13701087609', updateTime=1793340633627, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1322929760048906989, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1322912162913596032, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1322929760048906990, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1322912162913596032, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=128, endPage=133, ext={EN=ArticleExt(id=1322912244346007708, articleId=1322912243930771609, tenantId=1146029695717560320, journalId=1255847919539208197, language=EN, title=Research Progress on Effective Ingredients of Wumei Pill(乌梅丸)and Its Single Drug in Digestive System Diseases, columnId=1256183361521967297, journalTitle=Chinese Archives of Traditional Chinese Medicine, columnName=Target on National Project, runingTitle=null, highlight=null, articleAbstract=

Wumei Pill(乌梅丸)is recorded in Treatise on Cold Damage and Miscellaneous Diseases which is a traditional Chinese medicine classic during the Eastern Han Dynasty in China. It is said that“for those who suffer from roundworms and convulsions,Wumei Pill is the main treat mentmethod. It also can treat long-term diarrhea.”This formula is composed of 10 Chinese herbal medicines,including Wumei(Mume Fructus),Xixin(Asari Herba),Guizhi(Cinnamomi Ramulus),Huanglian(Coptidis Rhizoma),Huangbai(Phellodendri Cortex),Danggui(Angelicae Sinensis Radix),Ganjiang(Zingiberis Rhizoma),Fuzi(Aconiti Lateralis Preparata Radix),Renshen(Ginseng Radix)and Shujiao(Zanthoxyli Pericarpium). Itsmain efficacy is to warm liver and regulate themiddle,clear the upper and warm the lower parts. In clinical research,its modified formulae or combination with Western medicine are often used to treat multiple digestive system diseases such as ulcerative colitis,irritable bowel syndrome,chronic atrophic gastritis,gastroesophageal reflux disease,gastric cancer and intestinal polyps. Modern pharmacology shows that Wumei Pill plays important pharmacological roles in the treatment of gastrointestinal diseases,including anti-inflammatory,antioxidant,gastricmucosal protection,anti-tumor and antiulcer effects. This article used literature reports to summarize and generalize the effective ingredients of the formula from three aspects:clinical reports,pharmacological research on digestive system diseases and animal experiment reports. Based on the effective ingredients of the formula in relevant reports,the main effective ingredients of the formula used in common digestive system diseases were summarized,and the compatibility rules of the formula were explained through its pharmacological ingredients,in order to provide reference for the clinical application and related research of Wumei Pill.

, authors=Na REN, Xiuzhen HAN, Weiwei LIU, Yan LI, Shuihong LI, Hongtao SHANG, authorsList=Na REN, Xiuzhen HAN, Weiwei LIU, Yan LI, Shuihong LI, Hongtao SHANG, authorCompany=null, correspAuthors=Hongtao SHANG, 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=1322912245138731165, articleId=1322912243930771609, tenantId=1146029695717560320, journalId=1255847919539208197, language=CN, title=乌梅丸及其单味药有效成分在消化系统疾病中的研究进展, columnId=1256183362172142382, journalTitle=中华中医药学刊, columnName=国家项目点击, runingTitle=null, highlight=null, articleAbstract=

乌梅丸载于我国东汉时期的一部中医经典《伤寒杂病论》:“蛔厥者,乌梅丸主之。又主久利”,该方由乌梅、细辛、桂枝、黄连、黄柏、当归、干姜、附子、人参、蜀椒10种中药组成,其主要功效为暖肝调中,清上温下。临床研究中多以其加减方或联合西药治疗溃疡性结肠炎、肠易激综合征、慢性萎缩性胃炎、胃食管反流病、胃癌、肠息肉等多个消化系统疾病。现代药理学显示,乌梅丸治疗胃肠疾病发挥着抗炎、抗氧化、保护胃黏膜、抗肿瘤、抗溃疡等重要药理作用。借助文献报道,从该方临床报道、方剂组成中各药物有效成分与消化系统疾病药理研究、动物实验报道等三方面进行归纳总结,根据相关报道中该方的有效成分,总结出该方药物运用于常见消化系统疾病的主要有效成分,并通过其药理成分阐释该方的组方配伍规律,以期为乌梅丸临床应用及相关研究的开展提供参考。

, authors=任娜, 韩秀珍, 刘溦溦, 李岩, 李水洪, 商洪涛, authorsList=任娜, 韩秀珍, 刘溦溦, 李岩, 李水洪, 商洪涛, authorCompany=null, correspAuthors=商洪涛, authorNote=

任娜(1995-),女,河南信阳人,硕士在读,研究方向:中医脾胃病临床。

, correspAuthorsNote=
商洪涛(1967-),男,江苏连云港人,主任中医师,博士研究生导师,博士,研究方向:中医脾胃病临床和亚健康中医体质调理。E-mail:。
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任娜(1995-),女,河南信阳人,硕士在读,研究方向:中医脾胃病临床。

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任娜(1995-),女,河南信阳人,硕士在读,研究方向:中医脾胃病临床。

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Based Complement Alternat Med,2017,2017:3039450., articleTitle=Compound Wumei Powder inhibits the invasion and metastasis of gastric cancer via cox-2/PGE2-PI3K/AKT/GSK3β/β-catenin signaling pathway, refAbstract=null), Reference(id=1322912472935575941, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322912243930771609, doi=null, pmid=null, pmcid=null, year=2022, volume=2022, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[80], rfOrder=79, authorNames=WANG J, DING K, WANG Y H, journalName=Oxid Med Cell Longev, refType=null, unstructuredReference=WANG J,DING K,WANG Y H,et al.Wumei pill ameliorates AOM/DSS-induced colitis-associated colon cancer through inhibition of inflammation and oxidative stress by regulating S-adenosylhomocysteine hydrolase-(AHCY-)mediated hedgehog signaling in mice[J].Oxid Med Cell Longev,2022,2022:4061713., articleTitle=Wumei pill ameliorates AOM/DSS-induced colitis-associated colon cancer through inhibition of 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药物有效成分药理作用
乌梅豆甾醇抗炎、镇痛[25]
熊果酸抗炎[27]、抗肿瘤[28]
多糖调节免疫、抗氧化[29]
黄酮类抗炎、抗肿瘤[30]
黄连小檗碱抗炎[31]、保护胃黏膜[32]、抗氧化、抗肿瘤[33]
黄连碱抑菌[34]、保护胃黏膜[35]
多糖抗氧化[36]、抗炎[37]
黄柏黄酮抗氧化[38]、抗肿瘤[39]
黄柏碱抗氧化[40]、抗炎[41]
小檗碱抗炎[42]、抗肿瘤[43]
桂枝挥发油抗炎[44]、抗氧化[45]、抑菌[46]
桂枝醇抑菌[47]、镇痛、抗炎、抗病毒、抗过敏[48]
桂皮醛抗炎[51]、抗肿瘤[49-50]
干姜姜酚抗炎[55]、抑菌[54]
姜辣素抗炎[56]、抗氧化[57]
挥发油抗炎[58-59]
人参人参皂苷抗炎[62]、调节免疫[61]、抗肿瘤[60]
人参多糖抗氧化[64]、调节免疫[63]、抗肿瘤[65]
当归当归多糖抗氧化[68]、调节免疫、抗细胞凋亡、抗肿瘤、抗炎[66-67]
挥发油抗炎[71]、镇痛[70]
细辛甲基丁香酚抗氧化[73]、抗炎[72]
附子乌头碱抗炎[75]
花椒花椒果皮精油抗炎[76]
), ArticleFig(id=1322912460759511346, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322912243930771609, language=CN, label=表1, caption=

乌梅丸各药物作用于消化系统常见疾病的有效成分的药理作用汇总

, figureFileSmall=null, figureFileBig=null, tableContent=
药物有效成分药理作用
乌梅豆甾醇抗炎、镇痛[25]
熊果酸抗炎[27]、抗肿瘤[28]
多糖调节免疫、抗氧化[29]
黄酮类抗炎、抗肿瘤[30]
黄连小檗碱抗炎[31]、保护胃黏膜[32]、抗氧化、抗肿瘤[33]
黄连碱抑菌[34]、保护胃黏膜[35]
多糖抗氧化[36]、抗炎[37]
黄柏黄酮抗氧化[38]、抗肿瘤[39]
黄柏碱抗氧化[40]、抗炎[41]
小檗碱抗炎[42]、抗肿瘤[43]
桂枝挥发油抗炎[44]、抗氧化[45]、抑菌[46]
桂枝醇抑菌[47]、镇痛、抗炎、抗病毒、抗过敏[48]
桂皮醛抗炎[51]、抗肿瘤[49-50]
干姜姜酚抗炎[55]、抑菌[54]
姜辣素抗炎[56]、抗氧化[57]
挥发油抗炎[58-59]
人参人参皂苷抗炎[62]、调节免疫[61]、抗肿瘤[60]
人参多糖抗氧化[64]、调节免疫[63]、抗肿瘤[65]
当归当归多糖抗氧化[68]、调节免疫、抗细胞凋亡、抗肿瘤、抗炎[66-67]
挥发油抗炎[71]、镇痛[70]
细辛甲基丁香酚抗氧化[73]、抗炎[72]
附子乌头碱抗炎[75]
花椒花椒果皮精油抗炎[76]
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乌梅丸及其单味药有效成分在消化系统疾病中的研究进展
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任娜 , 韩秀珍 , 刘溦溦 , 李岩 , 李水洪 , 商洪涛
中华中医药学刊 | 国家项目点击 2025,43(1): 128-133
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中华中医药学刊 |国家项目点击 2025 , 43 (1) : 128 -133
乌梅丸及其单味药有效成分在消化系统疾病中的研究进展
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任娜, 韩秀珍, 刘溦溦, 李岩, 李水洪, 商洪涛
作者信息
  • 南京中医药大学附属医院,江苏 南京 210029
通讯作者:
商洪涛(1967-),男,江苏连云港人,主任中医师,博士研究生导师,博士,研究方向:中医脾胃病临床和亚健康中医体质调理。E-mail:。
作者简介:

任娜(1995-),女,河南信阳人,硕士在读,研究方向:中医脾胃病临床。

Research Progress on Effective Ingredients of Wumei Pill(乌梅丸)and Its Single Drug in Digestive System Diseases
Na REN, Xiuzhen HAN, Weiwei LIU, Yan LI, Shuihong LI, Hongtao SHANG
Affiliations
  • The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu, China
出版时间: 2025-01-10 doi: 10.13193/j.issn.1673-7717.2025.01.023
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乌梅丸载于我国东汉时期的一部中医经典《伤寒杂病论》:“蛔厥者,乌梅丸主之。又主久利”,该方由乌梅、细辛、桂枝、黄连、黄柏、当归、干姜、附子、人参、蜀椒10种中药组成,其主要功效为暖肝调中,清上温下。临床研究中多以其加减方或联合西药治疗溃疡性结肠炎、肠易激综合征、慢性萎缩性胃炎、胃食管反流病、胃癌、肠息肉等多个消化系统疾病。现代药理学显示,乌梅丸治疗胃肠疾病发挥着抗炎、抗氧化、保护胃黏膜、抗肿瘤、抗溃疡等重要药理作用。借助文献报道,从该方临床报道、方剂组成中各药物有效成分与消化系统疾病药理研究、动物实验报道等三方面进行归纳总结,根据相关报道中该方的有效成分,总结出该方药物运用于常见消化系统疾病的主要有效成分,并通过其药理成分阐释该方的组方配伍规律,以期为乌梅丸临床应用及相关研究的开展提供参考。

乌梅丸  /  有效成分  /  组方配伍  /  消化系统疾病  /  研究进展

Wumei Pill(乌梅丸)is recorded in Treatise on Cold Damage and Miscellaneous Diseases which is a traditional Chinese medicine classic during the Eastern Han Dynasty in China. It is said that“for those who suffer from roundworms and convulsions,Wumei Pill is the main treat mentmethod. It also can treat long-term diarrhea.”This formula is composed of 10 Chinese herbal medicines,including Wumei(Mume Fructus),Xixin(Asari Herba),Guizhi(Cinnamomi Ramulus),Huanglian(Coptidis Rhizoma),Huangbai(Phellodendri Cortex),Danggui(Angelicae Sinensis Radix),Ganjiang(Zingiberis Rhizoma),Fuzi(Aconiti Lateralis Preparata Radix),Renshen(Ginseng Radix)and Shujiao(Zanthoxyli Pericarpium). Itsmain efficacy is to warm liver and regulate themiddle,clear the upper and warm the lower parts. In clinical research,its modified formulae or combination with Western medicine are often used to treat multiple digestive system diseases such as ulcerative colitis,irritable bowel syndrome,chronic atrophic gastritis,gastroesophageal reflux disease,gastric cancer and intestinal polyps. Modern pharmacology shows that Wumei Pill plays important pharmacological roles in the treatment of gastrointestinal diseases,including anti-inflammatory,antioxidant,gastricmucosal protection,anti-tumor and antiulcer effects. This article used literature reports to summarize and generalize the effective ingredients of the formula from three aspects:clinical reports,pharmacological research on digestive system diseases and animal experiment reports. Based on the effective ingredients of the formula in relevant reports,the main effective ingredients of the formula used in common digestive system diseases were summarized,and the compatibility rules of the formula were explained through its pharmacological ingredients,in order to provide reference for the clinical application and related research of Wumei Pill.

Wumei Pill(乌梅丸)  /  active ingredients  /  prescription compatibility  /  digestive system diseases  /  research progress
任娜, 韩秀珍, 刘溦溦, 李岩, 李水洪, 商洪涛. 乌梅丸及其单味药有效成分在消化系统疾病中的研究进展. 中华中医药学刊, 2025 , 43 (1) : 128 -133 . DOI: 10.13193/j.issn.1673-7717.2025.01.023
Na REN, Xiuzhen HAN, Weiwei LIU, Yan LI, Shuihong LI, Hongtao SHANG. Research Progress on Effective Ingredients of Wumei Pill(乌梅丸)and Its Single Drug in Digestive System Diseases[J]. Chinese Archives of Traditional Chinese Medicine, 2025 , 43 (1) : 128 -133 . DOI: 10.13193/j.issn.1673-7717.2025.01.023
乌梅丸始载于我国东汉时期的一部中医经典《伤寒杂病论》:“蛔厥者,乌梅丸主之。又主久利”,原文中该方功效为温脏安蛔,用于治蛔厥、久利,但全方集酸甘化阴,辛苦通降,寒热并用,攻补兼施,刚柔互济,寒热虚实并调的同时兼能调和肝脾。现代药理学表明乌梅丸具有抗氧化应激、调控炎性因子、调控信号通路相关因子和蛋白表达、调节肠道菌群、抗肿瘤、调节免疫、促进肠黏膜修复等多种药理作用[1],可用来辨证治疗多个消化系统疾病[2],这也体现了中药复方多靶点、多机制、多效的治疗特点。本文将从该方的临床报道、方剂各组成药物治疗胃肠疾病的相关药理成分、动物实验报道三个方面进行归纳总结,并对乌梅丸各组成成分的药理之间的配伍规律进行阐释,为乌梅丸的进一步研究提供参考。
近年来,乌梅丸加减治疗慢性萎缩性胃炎的临床报道较之前有明显增长。艾灸联合乌梅丸治疗慢性萎缩性胃炎相关研究示艾灸联合乌梅丸的总有效率95.92%明显高于对比组西药组75.51% [3]。杨静波在研究中以观察组服用乌梅丸加三联药物,对照组单纯服用三联药物,治疗后乌梅丸西药三联总有效率为94.38%,高于对照组的82.95%,治疗后治疗组患者的白细胞介素(IL)-6、IL-8、肿瘤坏死因子-α(TNF-α)水平均明显低于对照组[4]。以上可见乌梅丸治疗慢性萎缩性胃炎作用明显,可以缓解慢性萎缩性胃炎患者的临床症状,提高患者机体免疫力,抗炎作用明显。
乌梅丸治疗胃食管反流病的临床研究总体较少,有关临床研究将胃食管反流病人随机分为观察组和对照组,对照组患者给予雷贝拉唑治疗,观察组患者在对照组基础上加服乌梅丸汤剂,治疗前和治疗8周后进行反流性疾病问卷评分并检测下食管括约肌静息压力和食管体部远端廓清能力,结果观察组患者总有效率显著高于对照组,乌梅丸对胃食管反流病主要临床症状有显著改善作用,并且能显著提高下食管括约肌张力、增强食管体部远端廓清能力[5]。王茜茜[6]通过临床研究发现加减乌梅丸方联合穴位针刺能改善食管动力,提高体部蠕动功能,促进缓解临床症状,提高治疗效果。以上皆说明乌梅丸在治疗胃食管反流病可以改善患者症状,提高患者的生活水平。
近年来,随着胃癌的发病率居高不下及中医药在治疗疑难病方面的广范应用,中医药治疗胃癌也出现了越来越多临床研究,但总体使用乌梅丸治疗胃癌的临床研究相对较少。张成晶从寒热错杂的病机出发论治胃癌,并将胃癌发生发展的基本病理过程总结为脾阳不振导致寒凝胃脉、气机阻滞、气滞血瘀、痰湿凝聚、久则成瘤,基于该理论将乌梅丸用于胃癌中晚期复发与转移的防治,他认为乌梅丸能通过有效地抑制胃癌及癌前病变中端粒酶的活性和增殖细胞核抗原(PCNA)的表达这一机制,从而干预胃癌前病变[7]。初世荣[8]通过临床研究发现乌梅丸加减治疗胃癌可显著改善胃癌患者腹胀、食少、嗳气、呕吐等症状,提高患者的生存质量,改善患者的红细胞、血红蛋白及血小板水平。总的来说,目前乌梅丸在治疗胃癌相关疾病的临床研究较少,未来可以从这个方面入手,为胃癌防治提供新思路。
溃疡性结肠炎为炎症性肠病的一种,其发病机制目前尚不明确,可能与遗传、免疫、肠道菌群、环境等因素有关,因此尚无治疗该病的特效药。其腹痛、腹泻、黏液脓血便的临床表现与乌梅丸“主久痢”有相通之处,因此临床研究中常用其治疗溃疡性结肠炎。近年来,关于乌梅丸运用于溃疡性结肠炎的临床报道较多。如李克亚[9]、王福英等[10]通过临床研究结果均显示乌梅丸联合美沙拉嗪相比于单用美沙拉嗪有效率更高,且更能显著改善溃疡性结肠炎患者的炎症反应和临床症状。杨静[11]通过临床研究发现柳氮磺吡啶联合乌梅丸加减治疗溃疡性结肠炎总有效率为93.10%,显著高于对照组单纯使用氮磺吡啶的77.50%。魏文先[12]通过临床研究发现泼尼松联合乌梅丸加减相对于单独使用泼尼松更能改善血清中炎性因子的水平,改善肠道菌群中各细菌的水平,提高有益菌的水平。以上报道发现西药联用乌梅丸比单纯西药治疗溃疡性结肠炎效果更佳。
肠易激综合征是临床常见的功能性肠病之一,可分为便秘型、腹泻型、混合型和不定型,其中腹泻型是其主要类型[13]。相对于其他型肠易激综合征,近年来乌梅丸运用于腹泻型肠易激综合征的临床研究较多,乌梅丸加减治疗腹泻型肠易激综合征的临床疗效优于常规西药治疗,而且复发率低,不良反应较少,在腹痛、腹泻症状改善方面较明显[14]。如黄秀杰[15]通过临床随机对照试验发现乌梅丸联合匹维溴铵治疗腹泻型肠易激综合征(寒热错杂)患者有效率为86.96%,明显高于对照组单纯运用匹维溴铵的65.22%,中医证候积分改善也明显高于对照组。马军[16]使用乌梅丸联合中药贴敷治疗寒热错杂腹泻型肠易激综合征临床试验结果显示治疗组胃肠道症状评分低于西药对照组,且认为中医治疗肠易激综合征的机理可能与调节辅助性T细胞1和2细胞因子平衡有关。由上可知,乌梅丸在治疗肠易激综合征具有临床意义。
随着胃肠镜的普及,近年来肠息肉的检出率明显增高,中医药对于肠息肉的预防也显得尤为重要,而运用乌梅丸治疗息肉的临床研究也呈增长趋势。有学者[17]认为脾胃虚弱,外邪及情志等因素导致胃肠寒热失调,痰瘀凝着是大肠息肉的病机特点,因此临床上强调已病防变,重视脾胃之健运,常采用乌梅丸加减以虚实兼顾、寒温并防治多发性大肠息肉,取得良好治疗效果。李烨等[18]认为肠息肉病位当属厥阴,病机重在阴阳气不相顺接、气机升降失常,并用乌梅丸以酸苦合法、寒温并用,温清并补,同时重用酸收以突出敛肝熄风之功效。徐燕[19]通过临床研究发现炎性增生性肠息肉患者经过内镜手术治疗后给予口服乌梅丸治疗,可有效预防出血及复发,利于肠道屏障功能的形成。曾英[20]将60例患者随机分为两组中药方剂乌梅丸为主方临症加减,对大肠息肉经肠镜下手术后进行治疗,对照组经肠镜下手术治疗后不做其他治疗,2年后大肠息肉再发率治疗组为20%,对照组为63%,并得出乌梅丸加减对大肠息肉经肠镜下手术治疗后再发有明显的预防作用的结论。
目前乌梅丸治疗肠癌及其相关疾病的临床研究相对较多,如杨琦[21]观察逍遥散合乌梅丸煎剂加减治疗大肠癌康复期胃肠功能紊乱的临床效果,发现逍遥散联合乌梅丸的总有效率为91.7%,显著高于西药对照组的66.7%,能明显改善患者食少纳呆、恶心呕吐、腹胀、腹痛、腹泻、便秘的症状。苏晓宇[22]通过120例直肠癌术后患者复的疗效情况及患者临床症状的改善情况研究发现乌梅丸治疗肝郁脾虚型直肠癌患者的6个月复发率最低为1.67%,且能显著改善临床症状,提高患者术后生活质量。代秋颖[23]通过对60例大肠腺瘤治疗后复发的临床研究发现乌梅丸能有效降低经内镜下治疗6月后大肠腺瘤复发率,并有效缓解大肠腺瘤患者黏液便或黏液血便、腹痛、便秘、腹胀的临床症状。以上报道可以说明乌梅丸在缓解各种肠癌术后的临床症状及降低肠癌患者术后的复发率方面有着重要作用,这为肠癌患者的术后治疗提供了中医药思路。
笔者通过检索相关临床报道发现,乌梅丸运用于治疗下消化道的疾病的临床研究明显高于上消化道的疾病,这可能与乌梅丸在原文中“主久利”的下消化道表现相一致,由此可见,中医药经方治疗疾病不具有时代局限,古方同样能今用,这对进一步挖掘古方,增加古方的使用率也是莫大的鼓励,同时这也为上消化道疾病的方剂选用提供新的研究思路。
由于现代科学技术的发展,越来越多的中药有效成分被提取出来,人们可以从其药理作用来阐释中药的作用机理,使中药组方中药物的疗效机制有了现代科学依据,这种发展模式符合中医中药现代化发展的大方向。验证方剂组方中各个药物有效成分与临床应用之间也是方剂研究的重要部分,而目前乌梅丸整方的有效成分药理研究尚少,多为单药有效成分药理研究。鉴于此,以下结合乌梅丸组方中各药物提取的有效成分在消化系统疾病中的药理作用进行分析。
乌梅的治疗消化系统疾病的主要有效药理成分包括有甾醇类、有机酸、多糖、黄酮类等,具有抑菌、抗氧化、抗肿瘤、调节肠道菌群等多种药理作用[24]。甾醇类中的豆甾醇具有抗炎镇痛活性,豆甾醇可以抑制κ基因结合核因(NF-κB)通路并下调NF-κB p60亚基的表达,这与活化的糖皮质激素受体介导NF-κB的反式抑制,阻止促炎介质的产生具有相通点,因此豆甾醇具有可能由糖皮质激素受体介导的抗炎作用[25]。有机酸中的熊果酸是一种具有药理和生物活性的天然产物,熊果酸及其异构体齐墩果酸是五环三萜酸类化合物,二者皆可以降低肠道病理损伤的风险,缓解肠道功能障碍,恢复肠道屏障功能[26],具有抗氧化、抗炎、抗溃疡、抗菌、抗病毒、抗癌、抗糖尿病等特性,且熊果酸可通过降低肠道菌群丰度、调节炎症和脂肪酸代谢信号通路影响免疫细胞浸润和细胞因子表达,从而治疗溃疡性结肠炎[27],也可有效抑制胃癌细胞的增殖和迁移,诱导其凋亡[28]。多糖类具有调节免疫功能、抗氧化的作用[29]。黄酮类具有抗炎、抗肿瘤等功效[30]。
黄连提取物中的生物碱、多糖是治疗消化系统疾病的主要成分。小檗碱为黄连主要生物碱,其药效在抗炎、抗菌、保护胃黏膜以及抗癌作用非常明显。小檗碱抗炎作用是通过抑制炎症因子IL-1β、TNF-α和一氧化氮的增加,抑制回肠Toll样受体4(TLR4)和NF-κB的活化,从而提高回肠超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)的活性从而减轻脂多糖诱导的肠损伤[31];小檗碱可抑制H+-K+-ATP酶活性,抑制胃酸分泌,保护胃黏膜,且能诱导有害肠道细菌的细胞凋亡,同时增强有益细菌的组成[32];此外,小檗碱可通过细胞毒作用抑制肿瘤细胞增殖、诱导细胞凋亡、增强机体免疫功能、调节细胞信号传导、抗氧化、诱导细胞分化等机制发挥抗肠道肿瘤作用[33]。黄连碱作为黄连的主要活性成分之一在胃肠疾病的特别是幽门螺杆菌的治疗方面运用广泛且治疗效果理想,黄连碱具有强大的抗幽门螺杆菌与脲酶的作用[34],显著降低幽门螺杆菌(HP)相关性胃炎大鼠胃黏膜的IL-6、IL-1β、TNF-α、磷酸化细胞外调节蛋白激酶(ERK1/2)蛋白含量,增加IL-10的含量,抑制HP引起的炎症反应对胃黏膜的损伤,保护胃黏膜[35]。而黄连中的药理成分多糖则具有抗氧化[36]、抗炎的作用[37]。
黄柏治疗消化系统疾病的有效药理成分为黄酮、黄柏碱、小檗碱。黄酮是一种天然生物活性化合物,具有强大的抗肿瘤和抗炎特点,研究发现,黄酮类化合物对肿瘤细胞有细胞毒作用,能抑制细胞信号转导过程中的酪氨酸蛋白激酶(TPK)活性,从而诱导肿瘤细胞凋零,并且对正常细胞有抗氧化和正面调节作用[38]。有关动物实验也表明黄酮能够通过抑制炎症反应和肿瘤细胞增殖来减轻结直肠癌[39]。黄柏碱具有抗氧化应激作用,相关研究发现黄柏碱可通过激活单磷酸腺苷活化蛋白激酶(AMPK)-雷帕霉素靶蛋白(mTOR)信号通路促进自噬,减轻溃疡性结肠炎结肠黏膜氧化应激,并最终对溃疡性结肠炎发挥保护作用[40]。黄柏碱还具有抗炎的作用,可以通过调控环磷酸腺苷、雌激素、TNF、血清素能突触等信号通路发挥抗炎作用[41]。小檗碱也具有抗炎[42]、抗癌[43]的作用。
桂枝挥发油、桂皮醇、桂皮醛为治疗消化系统疾病的主要成分。桂枝挥发油抗炎作用良好[44],且具有良好的抗氧化作用[45],另外对金黄色葡萄球菌、大肠杆菌具有较好的抑菌效果[46]。桂枝醇对伤寒病菌、霍乱弧菌及志贺痢疾杆菌等传染病病菌及大肠杆菌、枯草杆菌及金黄色葡萄糖球菌的体外生长具有良好的抑制作用[47],除此之外,桂枝醇还有解热镇痛、利尿、抗病毒、抗炎、抗过敏作用[48]。桂皮醛具有抗肿瘤作用[49-50],其机制与抑制肿瘤细胞增殖,诱导细胞凋亡有关,此外,桂皮醛还具有抗炎作用[51],能够保护肠黏膜,减少隐窝细胞的损伤以及炎症细胞浸润改善炎症。
干姜治疗消化系统疾病的主要药理成分为姜酚、挥发油、姜辣素,具有抗炎、抗肿瘤、抗菌、抗病原体、抗腹泻、利胆等作用[52],其中抗炎作用突出。现代医学研究证实姜酚有抗氧化、预防胃黏膜损伤、抗肿瘤、抗炎、抗溃疡、止呕、利胆等十几种生物活性[53],其中6-姜酚是生姜对HP的抑菌作用的主要活性成分之一,其体外抗HP的作用机理可能是6-姜酚与HP生长所需的一些酶的相互作用,抑制了HP的生长以致杀死HP[54]。另有研究表明6-姜酚可以通过降低血清和肠组织中的IL-17水平和增加IL-10水平来显著减轻炎症损伤,并可以通过抑制NF-κB信号通路抑制炎症损伤[55]。干姜姜辣素具有明显的抗炎活性[56]及抗氧化作用[57]。干姜挥发油具有抗炎作用[58],能降低炎症因子IL-6水平,升高抗炎因子IL-10水平抑制炎症反应[59]。
人参治疗消化系统疾病的主要成分是人参皂苷和人参多糖。人参皂苷发挥抗炎、抗癌、调节免疫的作用,有研究发现人参皂苷Rg3可通过促进胃腺癌细胞坏死、凋亡,并抑制癌细胞增殖、诱导胃癌细胞自噬来发挥对肿瘤的抑制作用的结论[60],人参皂苷也可增强肠黏膜上皮细胞增殖,调节免疫细胞分化和炎症因子产生,从而有效减轻炎症性肠病症状[61],人参皂苷Rh2可通过减少了促炎细胞因子,如TNF-α、IL-6和IL-1β来治疗溃疡性结肠炎[62]。人参的另一种成分人参多糖具有调节免疫、抗氧化衰老、抗肿瘤的作用,可以通过调节多种免疫细胞活性,在机体的固有免疫和获得性免疫中发挥重要作用[63];并可以提高SOD、GSH-Px、过氧化氢酶(CAT)活性及总抗氧化能力(T-AOC),发挥抗氧化衰老的作用[64];人参多糖还可以通过激活T细胞来间接抑制肿瘤细胞生长,起到抗肿瘤的作用[65]。
当归治疗消化系统疾病的主要成分为当归多糖和挥发油。当归多糖具有抗肿瘤、抗氧化、保肝、抗病毒、抗炎、造血、免疫调节、抗细胞凋亡和抑制血小板聚集等作用[66-67]。有研究表明当归多糖对二硝基苯磺酸引起的凋亡细胞数的增加有明显的抑制作用,且呈剂量依赖性,高剂量的当归多糖对减少凋亡细胞数有显著作用,除此之外,还发现当归多糖具有显著的抗氧化活性,能够降低结肠细胞氧化应激和减少细胞凋亡[68]。当归挥发油能够抑制人结直肠癌细胞HCT-116的增殖、迁移,诱导细胞凋亡,其机制可能与抑制Wnt/β-catenin信号通路有关,发挥抗肿瘤作用[69],此外当归挥发油还能发挥镇痛[70]、抗炎[71]作用。
中药药理学表明细辛具有解热、镇静、镇痛、抗炎、表面麻醉及浸润麻醉作用。细辛治疗胃肠疾病主要是通过其相关药性成分的抗炎、抗氧化来实现的,甲基丁香酚作为细辛药物主要成分之一,具有明显的抗炎作用,可用于缺血及炎症相关疾病[72]。有学者通过细胞实验探索甲基丁香酚对叔丁基氢过氧化物(t-BHP)引发的氧化损伤的抗氧化潜力以及抗氧化机制的参与,结果发现甲基丁香酚具有抑制炎症反应和氧化应激的作用,并可能通过激活AMPK/GSK3β-和ERK-Nrf2信号通路对t-BHP触发的细胞毒性发挥保护作用[73]。
中药药理学表明附子具有抗炎、镇痛、增强肌体抗氧化的能力。但附子有效成分中的双酯型生物碱毒性较大,包括乌头碱(AC)、次乌头碱(HA)、中乌头碱(MA)等,但经炮制其可转化成毒性较小的单酯型生物碱,包括苯甲酰乌头原碱(BAC)、苯甲酰次乌头原碱(BHA)、苯甲酰中乌头原碱(BMA)[74]。附子治疗胃肠疾病主要是通过抗炎作用来实现的,相关研究发现附子的3种单酯型生物碱BAC、BMA、BHA在一定剂量范围内能下调LPS刺激下巨噬细胞炎症因子TNF-α、IL-6的分泌量,此研究表明附子的成分可直接作用于免疫细胞发挥抗炎作用[75]。
花椒具有镇痛、镇静、抗炎、抑菌杀虫、抗肿瘤等作用,花椒在消化系统具有推进胃肠蠕动及抗溃疡作用。花椒果皮精油(ZBEO)对葡聚糖硫酸钠(DSS)诱导的小鼠实验性结肠炎的保护作用及机制,结果显示ZBEO降低了DSS引起的体质量减轻、疾病活动指数、结肠长度缩短、结肠病理损伤和过氧化物酶活性,并通过进一步的机理分析认为ZBEO通过调节NF-κB和PPARγ通路、抑制小鼠结肠炎中NLRP3的激活来抑制炎症[76]。此研究为溃疡性结肠炎患者提供一种新的饮食策略。
基于以上药理学研究及文献报道,将乌梅丸组成药物中治疗消化系统疾病的有效成分药理作用进行归纳总结。见表1。
通过对乌梅丸治疗各组成药物成分药理作用发现,其药物组成成分之间药理作用具有相同部分,也有部分药物具有不同药理作用,而同一药物的不同成分之间也具有相同及不同药理作用,这些药物成分之间体现一定的协同或者辅助的配伍规律。如乌梅中的豆甾醇、熊果酸、黄酮类具有抗炎作用,桂枝中的桂枝醇、桂皮醛均具有抗炎作用,干姜中的桂皮醛、姜酚、姜辣素均具有抗炎作用,这既体现了同一药物不同成分之间的协同作用以增强功效,也体现了不同药物之间的协同作用以增强功效,这与中药七情配伍中的“相须”具有异曲同工之妙。而针对具体的疾病而言,是以一种药理作用为主,其他药理作用为辅,如慢性萎缩性胃炎的治疗,则是以抗炎为主,其不同药物中的抗氧化、抑菌、调节免疫、保护胃黏膜,以及同一药物不同成分之间的抗氧化、抑菌、调节免疫、保护胃黏膜均为辅助治疗,这体现了中药七情配伍中的“相使”。此外乌梅丸中的不少药物成分的药理作用为调节免疫,这相当于中医中的扶正气,也是治本的体现;而药理作用中的抑菌相当于中医中的祛邪,这与中医治法中的治标具有一致性。脾胃为后天之本,治病必求于本,故当匡扶正气,同时胃肠疾病的发生与幽门螺杆菌、大肠杆菌等病邪的入侵密切相关,故乌梅丸的配伍严谨与胃肠疾病的发病特点对应。
动物实验是基础研究的重要部分,乌梅丸作为治疗胃肠疾病的经典方剂,其在治疗消化系统的相关动物实验也有了一定进展。丁晓洁等[77]通过大鼠动物实验发现乌梅丸治疗作用腹泻型肠易激综合征的机制与调节肠道菌群和降低血清促炎因子TNF-α和IL-6的含量有关,并猜测乌梅丸是通过提高双歧杆菌/肠杆菌(B/E)值达到调整肠道菌群结构、抑制炎症反应、降低肠道敏感性,因此能够缓解腹泻型肠易激综合征腹痛、腹泻症状。张静[78]通过研究乌梅丸及其拆方对溃疡性结肠炎大鼠的治疗效果发现,乌梅丸可通过抑制溃疡性结肠炎模型大鼠的结肠黏膜组织两面神激酶(Jak)、信号传导及转录激活蛋白3(STAT3)、IL-6的异常激活,从而改善肠道的溃疡大小、炎症程度及病变深度,因此可以认为乌梅丸能够改善溃疡性结肠炎大鼠结肠黏膜炎症浸润,从而达到对溃疡性结肠炎的治疗效果。有学者通过细胞及动物实验观察乌梅丸对胃癌的影响,结果认为乌梅丸可能是通过Cox-2/PGE2-PI3K/AKT/GSK3β/β-Catenin信号通路抑制肿瘤细胞的侵袭和转移[79]。WANG J等[80]通过动物实验发现乌梅丸通过调节S-腺苷同型半胱氨酸水解酶介导的hedgehog信号传导,来抑制炎症和氧化应激,从而减轻氧化偶氮甲烷/DSS诱导的结肠炎相关结肠癌。以上动物实验说明乌梅丸在治疗消化系统疾病可发挥抗炎作用,与临床研究具有一致性。
乌梅丸古方原为治疗蛔厥及下利的专方,今在其基础上加减或联合西药治疗多个消化系统的疾病并取得良好的疗效,这是中医经典古为今用的体现,同时关于乌梅丸治疗消化系统的临床疾病的临床及动物研究都多以合方或者辅助西医治疗为主,这也体现了中西医结合发展大趋势,这种联合治疗的方式效果突出,安全有效,能够通过抗炎、抗氧化等作用,减轻消化系统疾病的临床症状,改善客观指标,是一种值得广泛推广的方法。另外近年来不管是对乌梅丸的临床研究还是动物研究,多集中在下消化道系统的疾病,特别是腹泻相关的疾病,如溃疡性结肠炎、肠癌等,这可能与原文中“主久利”相关,同时这种现象也反映了在运用古方时存在局限于“辨症”论治,也提示我们要考虑其病机“辨证”论治,扩大乌梅丸的应用范围。
中医经典方剂的现代药理学研究关乎中医现代化进程,但目前对于该方的整体有效成分的研究较少,多集中于单味药有效成分的药理研究。本文基于文献报道,根据药理作用对乌梅丸各组成药物有效成分提取和筛选,总结出其治疗消化系统的有效成分,乌梅丸可发挥抗炎、抗肿瘤、调节免疫、抗菌、保护胃肠黏膜、抗病毒等多重药理作用。通过对其组成药物相同及不同的药理作用配伍规律的阐释,为乌梅丸运用于临床提供了现代医学的依据。
方剂学的发展与临床研究、动物实验、中药药理研究密切相关,乌梅丸作为张仲景的经典名方之一,对于治疗胃肠疾病具有极大的研究价值,而目前的临床研究及动物实验相对较多,但大多集中在下消化道,对上消化道的研究报道数量相对较少,故乌梅丸治疗上消化道相关疾病仍有很大的研究空间。另外,对于该方的药理学研究多集中在单药上,整方的研究相对较少,故对乌梅丸相关药理学研究仍有很大的进步空间,尤其是整方的有效成分提取及药理学方面,需要更深入地研究来挖掘。
  • 国家自然科学基金青年科学基金项目(81904122)
  • 江苏省老年医学临床技术应用研究项目(LD2021004)
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2025年第43卷第1期
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doi: 10.13193/j.issn.1673-7717.2025.01.023
  • 首发时间:2026-10-30
  • 出版时间:2025-01-10
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国家自然科学基金青年科学基金项目(81904122)
江苏省老年医学临床技术应用研究项目(LD2021004)
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    南京中医药大学附属医院,江苏 南京 210029

通讯作者:

商洪涛(1967-),男,江苏连云港人,主任中医师,博士研究生导师,博士,研究方向:中医脾胃病临床和亚健康中医体质调理。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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