Article(id=1304415547710526355, tenantId=1146029695717560320, journalId=1302319053441957962, issueId=1304415531491152712, articleNumber=null, orderNo=null, doi=10.7501/j.issn.0253-2670.2026.09.013, pmid=null, cstr=null, oa=null, hot=0, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1763481600000, receivedDateStr=2025-11-19, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1788926501443, onlineDateStr=2026-09-09, pubDate=null, pubDateStr=null, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1788926501443, onlineIssueDateStr=2026-09-09, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1788926501443, creator=13701087609, updateTime=1788926501443, updator=13701087609, issue=Issue{id=1304415531491152712, tenantId=1146029695717560320, journalId=1302319053441957962, year='2026', volume='57', issue='9', pageStart='3261', pageEnd='3684', issueExtLink='null', onlineDate='null', pubDate='1778515200000', pubDateStr='2026-05-12', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1788926497576, creator='13701087609', updateTime=1788926796984, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1304416787358049066, tenantId=1146029695717560320, journalId=1302319053441957962, issueId=1304415531491152712, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1304416787358049067, tenantId=1146029695717560320, journalId=1302319053441957962, issueId=1304415531491152712, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=3399, endPage=3413, ext={EN=ArticleExt(id=1304415549656683413, articleId=1304415547710526355, tenantId=1146029695717560320, journalId=1302319053441957962, language=EN, title=Banxia Xiexin Decoction prevents and treats colorectal cancer by improving immune microenvironment via regulating farnesoid X receptor-mediated bile acid metabolism, columnId=null, journalTitle=Chinese Traditional and Herbal Drugs, columnName=null, runingTitle=null, highlight=null, articleAbstract=Objective To investigate the preventive and therapeutic effects of Banxia Xiexin Decoction (半夏泻心汤, BXD) on colorectal cancer (CRC) and its underlying mechanism based on “farnesoid X receptor (FXR)-bile acid-immune microenvironment” axis. Methods A mouse CRC model was established by intraperitoneal injection of azoxymethane combined with oral administration of dextran sulfate sodium (DSS). Control group, model group, BXD low-, medium-, high-dose (3.915, 7.830, 15.660 g/kg) groups and mesalazine (0.6 g/kg) group were set up, with 10 mice in each group. Drugs were continuously given for eight weeks, general condition of mice was recorded. Histopathological changes in colon tissue were observed. Immunofluorescence staining was used to examine the distribution and expressions of CD11c, CD80 and CD86 in colon tissue. Flow cytometry was employed to detect the expressions of CD11b, CD11c, CD80, CD86 and CD206 in spleen tissue. Targeted metabolomics was used to analyze the levels of bile acids in feces of mice. Levels of interferon-γ (IFN-γ), interleukin-12 (IL-12), IL-18, total bile acids in serum and total bile acids in bile were detected. qRT-PCR was performed to measure the mRNA expressions of FXR, fibroblast growth factor 15 (FGF15), G protein-coupled receptor 41 (GPR41), GPR43, GPR109A, histone deacetylase 3 (HDAC3), HDAC7, inducible nitric oxide synthase (iNOS), IL-12, epidermal growth factor (EGF) and transforming growth factor-β1 (TGF-β1) in colon tissue. Western blotting was used to detect the protein expressions of FXR, iNOS, IL-12, EGF, TGF-β1, FGF15, GPR41, GPR43 and GPR109A in colon tissue. Results Compared with control group, the model group showed significant weight loss, increased number and size of colon tumors, severe disruption of glandular structure, irregular hyperplasia and distortion, formation of gland-like or nest-like structures, accompanied by marked inflammatory cell infiltration and tissue damage. PAS-positive substances were focally aggregated, distributed disorderly with irregular morphology. CD11c+ cells were extensively aggregated in colon tumor tissue, while CD80+ cells showed almost no fluorescence. The expressions of CD11b, CD11c and CD80 in spleen tissue was significantly increased (P < 0.01). Levels of deoxycholic acid (DCA), lithocholic acid (LCA) and taurocholic acid (TCA) in fecal were significantly elevated (P < 0.01). Protein expressions of iNOS, IL-12, EGF, TGF-β1, HDAC7 and HDAC3 in colon tissue were significantly increased (P < 0.01), while protein expressions of FXR, FGF15, GPR41, GPR43 and GPR109A were significantly decreased (P < 0.01). Compared with model group, the changes in the above indicators were reversed in both BXD and mesalazine groups, and the changes were more pronounced in BXD high-dose group (P < 0.05, 0.01). Conclusion BXD may exert its preventive and therapeutic effects on colorectal cancer by activating FXR signaling pathway, regulating bile acid metabolic homeostasis, and subsequently reshaping the tumor immune microenvironment., authors=CUI Tingting, YUE Yinzi, HUANG Yuming, SUN Mingming, FENG Huayi, SU Lianlin, YAN Shuai, authorsList=CUI Tingting, YUE Yinzi, HUANG Yuming, SUN Mingming, FENG Huayi, SU Lianlin, YAN Shuai, authorCompany=null, correspAuthors=null, 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=1304415549543437204, articleId=1304415547710526355, tenantId=1146029695717560320, journalId=1302319053441957962, language=CN, title=半夏泻心汤通过调控法尼醇X受体介导的胆汁酸代谢改善免疫微环境防治结直肠癌, columnId=1304140191707456168, journalTitle=中草药, columnName=药理与临床, runingTitle=null, highlight=null, articleAbstract=目的 基于“法尼醇X受体(farnesoid X receptor,FXR)-胆汁酸-免疫微环境”轴,探讨半夏泻心汤对结直肠癌的防治作用与机制。方法 采用ip氧化偶氮甲烷(azoxymethane,AOM)联合自由饮用葡聚糖硫酸钠盐(dextran sulfate sodium,DSS)法制备小鼠结直肠癌(colorectal cancer,CRC)模型。设置为对照组、模型组及半夏泻心汤低、中、高剂量(3.915、7.830、15.660 g/kg)组和美沙拉嗪(0.6 g/kg)组,每组10只。连续给药干预8周,记录小鼠一般情况;观察小鼠结肠组织病理学变化;免疫荧光染色观察结肠组织中CD11c、CD80、CD86的分布及表达;流式细胞术检测脾脏组织中CD11b、CD11c、CD80、CD86和CD206的表达;靶向代谢组学分析小鼠粪便中胆汁酸水平;检测血清中γ干扰素(interferon-γ,IFN-γ)、白细胞介素-12(interleukin-12,IL-12)、IL-18、总胆汁酸及胆汁总胆汁酸水平;qRT-PCR检测结肠组织FXR、成纤维细胞生长因子(fibroblast growth factor 15,FGF15)、G蛋白偶联受体41(G protein-coupled receptor 41,GPR41)、GPR43GPR109A、组蛋白去乙酰化酶3(histone deacetylase 3,HDAC3)、HDAC7、诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)、IL-12、表皮生长因子(epidermal growth factor,EGF)和转化生长因子-β1(transforming growth factor-β1,TGF-β1)的mRNA表达;Western blotting检测结肠组织FXR、iNOS、IL-12、EGF、TGF-β1、FGF15、GPR41、GPR43和GPR109A蛋白表达。结果 与对照组比较,模型组小鼠体质量明显减轻,结肠瘤体数目增多、体积增大,组织病理学可见模型组小鼠腺体结构严重紊乱,出现不规则增生、扭曲,甚至形成腺样或巢状结构,同时伴随明显的炎症细胞浸润和组织破坏,PAS阳性物质呈局灶性大量聚集,分布紊乱且形态不规则;结肠肿瘤组织中CD11c⁺细胞大量聚集,CD80⁺细胞减少;脾脏组织中CD11b、CD11c和CD80表达显著升高(P<0.01);粪便中脱氧胆酸(deoxycholic acid,DCA)、石胆酸(lithocholic acid,LCA)、牛磺胆酸(taurocholic acid,TCA)水平显著升高(P<0.01);结肠组织中iNOS、IL-12、EGF、TGF-β1、HDAC7和HDAC3表达明显升高(P<0.01),FXR、FGF15、GPR41、GPR43、GPR109A表达明显降低(P<0.01)。与模型组比较,半夏泻心汤和美沙拉嗪组上述指标的变化均发生逆转,且以半夏泻心汤高剂量组变化更为显著(P<0.05、0.01)。结论 半夏泻心汤可能通过激活FXR信号通路,调节胆汁酸代谢稳态,进而重塑肿瘤免疫微环境,最终发挥防治结直肠癌的作用。, authors=崔停停1, 乐音子2, 黄玉明2, 孙明明1, 冯华夷1, 苏联麟3, 颜帅1, authorsList=崔停停, 乐音子, 黄玉明, 孙明明, 冯华夷, 苏联麟, 颜帅, authorCompany=1 南京中医药大学附属苏州市中医医院 肛肠科, 江苏 苏州 215009;
2 南京中医药大学附属苏州市中医医院 普外科, 江苏 苏州 215009;
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半夏泻心汤通过调控法尼醇X受体介导的胆汁酸代谢改善免疫微环境防治结直肠癌
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中草药 | 药理与临床 2026,57(9): 3399-3413
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中草药 |药理与临床 2026 , 57 (9) : 3399 -3413
半夏泻心汤通过调控法尼醇X受体介导的胆汁酸代谢改善免疫微环境防治结直肠癌
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崔停停1, 乐音子2, 黄玉明2, 孙明明1, 冯华夷1, 苏联麟3, 颜帅1
作者信息
    1 南京中医药大学附属苏州市中医医院 肛肠科, 江苏 苏州 215009;
    2 南京中医药大学附属苏州市中医医院 普外科, 江苏 苏州 215009;
    3 南京中医药大学药学院, 江苏 南京 210023
通讯作者:
颜帅
作者简介:
崔停停: 崔停停(2000-),女,硕士研究生,从事中医药防治肛肠疾病的临床研究。E-mail:15729904306@163.com
Banxia Xiexin Decoction prevents and treats colorectal cancer by improving immune microenvironment via regulating farnesoid X receptor-mediated bile acid metabolism
  • CUI Tingting, YUE Yinzi, HUANG Yuming, SUN Mingming, FENG Huayi, SU Lianlin, YAN Shuai
  • Affiliations
    doi: 10.7501/j.issn.0253-2670.2026.09.013
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    目的 基于“法尼醇X受体(farnesoid X receptor,FXR)-胆汁酸-免疫微环境”轴,探讨半夏泻心汤对结直肠癌的防治作用与机制。方法 采用ip氧化偶氮甲烷(azoxymethane,AOM)联合自由饮用葡聚糖硫酸钠盐(dextran sulfate sodium,DSS)法制备小鼠结直肠癌(colorectal cancer,CRC)模型。设置为对照组、模型组及半夏泻心汤低、中、高剂量(3.915、7.830、15.660 g/kg)组和美沙拉嗪(0.6 g/kg)组,每组10只。连续给药干预8周,记录小鼠一般情况;观察小鼠结肠组织病理学变化;免疫荧光染色观察结肠组织中CD11c、CD80、CD86的分布及表达;流式细胞术检测脾脏组织中CD11b、CD11c、CD80、CD86和CD206的表达;靶向代谢组学分析小鼠粪便中胆汁酸水平;检测血清中γ干扰素(interferon-γ,IFN-γ)、白细胞介素-12(interleukin-12,IL-12)、IL-18、总胆汁酸及胆汁总胆汁酸水平;qRT-PCR检测结肠组织FXR、成纤维细胞生长因子(fibroblast growth factor 15,FGF15)、G蛋白偶联受体41(G protein-coupled receptor 41,GPR41)、GPR43GPR109A、组蛋白去乙酰化酶3(histone deacetylase 3,HDAC3)、HDAC7、诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)、IL-12、表皮生长因子(epidermal growth factor,EGF)和转化生长因子-β1(transforming growth factor-β1,TGF-β1)的mRNA表达;Western blotting检测结肠组织FXR、iNOS、IL-12、EGF、TGF-β1、FGF15、GPR41、GPR43和GPR109A蛋白表达。结果 与对照组比较,模型组小鼠体质量明显减轻,结肠瘤体数目增多、体积增大,组织病理学可见模型组小鼠腺体结构严重紊乱,出现不规则增生、扭曲,甚至形成腺样或巢状结构,同时伴随明显的炎症细胞浸润和组织破坏,PAS阳性物质呈局灶性大量聚集,分布紊乱且形态不规则;结肠肿瘤组织中CD11c⁺细胞大量聚集,CD80⁺细胞减少;脾脏组织中CD11b、CD11c和CD80表达显著升高(P<0.01);粪便中脱氧胆酸(deoxycholic acid,DCA)、石胆酸(lithocholic acid,LCA)、牛磺胆酸(taurocholic acid,TCA)水平显著升高(P<0.01);结肠组织中iNOS、IL-12、EGF、TGF-β1、HDAC7和HDAC3表达明显升高(P<0.01),FXR、FGF15、GPR41、GPR43、GPR109A表达明显降低(P<0.01)。与模型组比较,半夏泻心汤和美沙拉嗪组上述指标的变化均发生逆转,且以半夏泻心汤高剂量组变化更为显著(P<0.05、0.01)。结论 半夏泻心汤可能通过激活FXR信号通路,调节胆汁酸代谢稳态,进而重塑肿瘤免疫微环境,最终发挥防治结直肠癌的作用。
    半夏泻心汤  /  结直肠癌  /  法尼醇X受体  /  免疫  /  肿瘤微环境  /  小檗碱  /  黄芩苷  /  甘草酸  /  黄连碱  /  巴马汀
    Objective To investigate the preventive and therapeutic effects of Banxia Xiexin Decoction (半夏泻心汤, BXD) on colorectal cancer (CRC) and its underlying mechanism based on “farnesoid X receptor (FXR)-bile acid-immune microenvironment” axis. Methods A mouse CRC model was established by intraperitoneal injection of azoxymethane combined with oral administration of dextran sulfate sodium (DSS). Control group, model group, BXD low-, medium-, high-dose (3.915, 7.830, 15.660 g/kg) groups and mesalazine (0.6 g/kg) group were set up, with 10 mice in each group. Drugs were continuously given for eight weeks, general condition of mice was recorded. Histopathological changes in colon tissue were observed. Immunofluorescence staining was used to examine the distribution and expressions of CD11c, CD80 and CD86 in colon tissue. Flow cytometry was employed to detect the expressions of CD11b, CD11c, CD80, CD86 and CD206 in spleen tissue. Targeted metabolomics was used to analyze the levels of bile acids in feces of mice. Levels of interferon-γ (IFN-γ), interleukin-12 (IL-12), IL-18, total bile acids in serum and total bile acids in bile were detected. qRT-PCR was performed to measure the mRNA expressions of FXR, fibroblast growth factor 15 (FGF15), G protein-coupled receptor 41 (GPR41), GPR43, GPR109A, histone deacetylase 3 (HDAC3), HDAC7, inducible nitric oxide synthase (iNOS), IL-12, epidermal growth factor (EGF) and transforming growth factor-β1 (TGF-β1) in colon tissue. Western blotting was used to detect the protein expressions of FXR, iNOS, IL-12, EGF, TGF-β1, FGF15, GPR41, GPR43 and GPR109A in colon tissue. Results Compared with control group, the model group showed significant weight loss, increased number and size of colon tumors, severe disruption of glandular structure, irregular hyperplasia and distortion, formation of gland-like or nest-like structures, accompanied by marked inflammatory cell infiltration and tissue damage. PAS-positive substances were focally aggregated, distributed disorderly with irregular morphology. CD11c+ cells were extensively aggregated in colon tumor tissue, while CD80+ cells showed almost no fluorescence. The expressions of CD11b, CD11c and CD80 in spleen tissue was significantly increased (P < 0.01). Levels of deoxycholic acid (DCA), lithocholic acid (LCA) and taurocholic acid (TCA) in fecal were significantly elevated (P < 0.01). Protein expressions of iNOS, IL-12, EGF, TGF-β1, HDAC7 and HDAC3 in colon tissue were significantly increased (P < 0.01), while protein expressions of FXR, FGF15, GPR41, GPR43 and GPR109A were significantly decreased (P < 0.01). Compared with model group, the changes in the above indicators were reversed in both BXD and mesalazine groups, and the changes were more pronounced in BXD high-dose group (P < 0.05, 0.01). Conclusion BXD may exert its preventive and therapeutic effects on colorectal cancer by activating FXR signaling pathway, regulating bile acid metabolic homeostasis, and subsequently reshaping the tumor immune microenvironment.
    Banxia Xiexin Decoction  /  colorectal cancer  /  farnesoid X receptor  /  immunity  /  tumor microenvironment  /  berberine  /  baicalin  /  glycyrrhizic acid  /  coptisine  /  palmatine
    崔停停, 乐音子, 黄玉明, 孙明明, 冯华夷, 苏联麟, 颜帅. 半夏泻心汤通过调控法尼醇X受体介导的胆汁酸代谢改善免疫微环境防治结直肠癌. 中草药, 2026 , 57 (9) : 3399 -3413 . DOI: 10.7501/j.issn.0253-2670.2026.09.013
    CUI Tingting, YUE Yinzi, HUANG Yuming, SUN Mingming, FENG Huayi, SU Lianlin, YAN Shuai. Banxia Xiexin Decoction prevents and treats colorectal cancer by improving immune microenvironment via regulating farnesoid X receptor-mediated bile acid metabolism[J]. Chinese Traditional and Herbal Drugs, 2026 , 57 (9) : 3399 -3413 . DOI: 10.7501/j.issn.0253-2670.2026.09.013

      国家自然科学基金青年科学基金资助项目(82104565);天津中医药大学组分中药国家重点实验室青苗基金资助项目(QMJJ202403)

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