• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

非靶向代谢组学揭示大黄在胆汁淤积大鼠模型中作用的剂量反应特征。

Untargeted Metabolomics Reveals Dose-Response Characteristics for Effect of Rhubarb in a Rat Model of Cholestasis.

作者信息

Zhang Cong-En, Niu Ming, Li Rui-Yu, Feng Wu-Wen, Ma Xiao, Dong Qin, Ma Zhi-Jie, Li Guang-Quan, Meng Ya-Kun, Wang Ya, Yin Ping, He Lan-Zhi, Li Yu-Meng, Tan Peng, Zhao Yan-Ling, Wang Jia-Bo, Dong Xiao-Ping, Xiao Xiao-He

机构信息

College of Pharmacy, Chengdu University of Traditional Chinese MedicineChengdu, China; China Military Institute of Chinese Medicine, 302 Military HospitalBeijing, China.

China Military Institute of Chinese Medicine, 302 Military Hospital Beijing, China.

出版信息

Front Pharmacol. 2016 Mar 31;7:85. doi: 10.3389/fphar.2016.00085. eCollection 2016.

DOI:10.3389/fphar.2016.00085
PMID:27065293
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4814850/
Abstract

Cholestasis is a serious manifestation of liver diseases with limited therapies. Rhubarb, a widely used herbal medicine, has been frequently used at a relatively large dose for treating cholestasis. However, whether large doses are optimal and the therapeutic mechanism remain unclear. To explore these questions, the anti-cholestatic effect of five doses of rhubarb (0.21, 0.66, 2.10, 6.60, and 21.0 g/kg) in an alpha-naphthylisothiocyanate (ANIT)-induced rat model of cholestasis was examined by histopathology and serum biochemistry. A dose-dependent anti-cholestatic effect of rhubarb (0.21-6.6 g/kg) was observed, and an overdose of 21.0 g/kg showed a poor effect. LC-MS-based untargeted metabolomics together with pathway analysis were further applied to characterize the metabolic alterations induced by the different rhubarb doses. Altogether, 13 biomarkers were identified. The dose-response curve based on nine important biomarkers indicated that doses in the 0.42-6.61 g/kg range (EC20-EC80 range, corresponding to 4.00-62.95 g in the clinic) were effective for cholestasis treatment. The pathway analysis showed that bile acid metabolism and excretion, inflammation and amino acid metabolism were altered by rhubarb in a dose-dependent manner and might be involved in the dose-response relationship and therapeutic mechanism of rhubarb for cholestasis treatment.

摘要

胆汁淤积是肝脏疾病的一种严重表现，治疗方法有限。大黄是一种广泛使用的草药，经常以相对较大的剂量用于治疗胆汁淤积。然而，大剂量是否最佳以及治疗机制仍不清楚。为了探究这些问题，通过组织病理学和血清生物化学方法，研究了五剂大黄（0.21、0.66、2.10、6.60和21.0克/千克）在α-萘异硫氰酸酯（ANIT）诱导的大鼠胆汁淤积模型中的抗胆汁淤积作用。观察到大黄（0.21 - 6.6克/千克）具有剂量依赖性的抗胆汁淤积作用，而21.0克/千克的过量剂量效果不佳。基于液相色谱-质谱联用的非靶向代谢组学以及通路分析进一步用于表征不同大黄剂量诱导的代谢变化。总共鉴定出13种生物标志物。基于9种重要生物标志物的剂量-反应曲线表明，0.42 - 6.61克/千克范围内的剂量（EC20 - EC80范围，相当于临床中的4.00 - 62.95克）对胆汁淤积治疗有效。通路分析表明，大黄以剂量依赖性方式改变胆汁酸代谢和排泄以及炎症和氨基酸代谢，这可能与大黄治疗胆汁淤积的剂量-反应关系和治疗机制有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b3a/4814850/3c54a9471cdc/fphar-07-00085-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b3a/4814850/0b22dbda1622/fphar-07-00085-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b3a/4814850/268ce3df9877/fphar-07-00085-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b3a/4814850/e3ecb6586c2c/fphar-07-00085-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b3a/4814850/61048a53d257/fphar-07-00085-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b3a/4814850/eacdb9f479d3/fphar-07-00085-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b3a/4814850/04a682536738/fphar-07-00085-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b3a/4814850/3c54a9471cdc/fphar-07-00085-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b3a/4814850/0b22dbda1622/fphar-07-00085-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b3a/4814850/268ce3df9877/fphar-07-00085-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b3a/4814850/e3ecb6586c2c/fphar-07-00085-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b3a/4814850/61048a53d257/fphar-07-00085-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b3a/4814850/eacdb9f479d3/fphar-07-00085-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b3a/4814850/04a682536738/fphar-07-00085-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b3a/4814850/3c54a9471cdc/fphar-07-00085-g0007.jpg

相似文献

1
Untargeted Metabolomics Reveals Dose-Response Characteristics for Effect of Rhubarb in a Rat Model of Cholestasis.非靶向代谢组学揭示大黄在胆汁淤积大鼠模型中作用的剂量反应特征。
Front Pharmacol. 2016 Mar 31;7:85. doi: 10.3389/fphar.2016.00085. eCollection 2016.
2
An integrated metabolomics strategy to reveal dose-effect relationship and therapeutic mechanisms of different efficacy of rhubarb in constipation rats.采用代谢组学策略揭示大黄不同疗效在治疗便秘大鼠中的量效关系和作用机制。
J Pharm Biomed Anal. 2020 Jan 5;177:112837. doi: 10.1016/j.jpba.2019.112837. Epub 2019 Aug 26.
3
UPLC-MS-based metabonomic analysis of intervention effects of Da-Huang-Xiao-Shi decoction on ANIT-induced cholestasis.基于 UPLC-MS 的大黄硝石汤干预对 ANIT 诱导的胆汁淤积症的代谢组学分析。
J Ethnopharmacol. 2019 Jun 28;238:111860. doi: 10.1016/j.jep.2019.111860. Epub 2019 Apr 6.
4
Integrated 16 S rRNA gene sequencing and serum metabolomics approaches to decipher the mechanism of Qingre Lidan decoction in the treatment of cholestatic liver injury.采用 16S rRNA 基因测序和血清代谢组学方法解析清热利胆汤治疗胆汁淤积性肝损伤的作用机制。
J Pharm Biomed Anal. 2023 Sep 20;234:115535. doi: 10.1016/j.jpba.2023.115535. Epub 2023 Jun 16.
5
Synergistic effects of rhubarb-gardenia herb pair in cholestatic rats at pharmacodynamic and pharmacokinetic levels.大黄-栀子药对在胆汁淤积大鼠体内药效学和药代动力学水平的协同作用。
J Ethnopharmacol. 2015 Dec 4;175:67-74. doi: 10.1016/j.jep.2015.09.012. Epub 2015 Sep 13.
6
Evaluation of the protective effect of Zhi-Zi-da-Huang decoction on acute liver injury with cholestasis induced by α-naphthylisothiocyanate in rats.栀子大黄汤对α-萘异硫氰酸酯诱导的大鼠急性胆汁淤积性肝损伤保护作用的评价
J Ethnopharmacol. 2015 Aug 22;172:402-9. doi: 10.1016/j.jep.2015.06.043. Epub 2015 Jul 7.
7
Paeonia lactiflora Pall. protects against ANIT-induced cholestasis by activating Nrf2 via PI3K/Akt signaling pathway.芍药通过PI3K/Akt信号通路激活Nrf2，从而对ANIT诱导的胆汁淤积起到保护作用。
Drug Des Devel Ther. 2015 Sep 2;9:5061-74. doi: 10.2147/DDDT.S90030. eCollection 2015.
8
Protective effect of Danning tablet on acute livery injury with cholestasis induced by α-naphthylisothiocyanate in rats.丹宁片对α-萘异硫氰酸酯诱导的大鼠急性胆汁淤积性肝损伤的保护作用。
J Ethnopharmacol. 2012 Mar 27;140(2):222-9. doi: 10.1016/j.jep.2011.12.047. Epub 2012 Jan 16.
9
Investigations of the total flavonoids extracted from flowers of Abelmoschus manihot (L.) Medic against α-naphthylisothiocyanate-induced cholestatic liver injury in rats.黄蜀葵花总黄酮对大鼠α-萘异硫氰酸酯诱导的胆汁淤积性肝损伤的研究
J Ethnopharmacol. 2015 Aug 22;172:202-13. doi: 10.1016/j.jep.2015.06.044. Epub 2015 Jun 30.
10
Elucidating dosage-effect relationship of different efficacy of rhubarb in constipation model rats by factor analysis.通过因子分析阐明大黄在便秘模型大鼠中不同疗效的剂量-效应关系。
J Ethnopharmacol. 2019 Jun 28;238:111868. doi: 10.1016/j.jep.2019.111868. Epub 2019 Apr 11.

引用本文的文献

1
The Water Extract of Rhubarb Prevents Ischemic Stroke by Regulating Gut Bacteria and Metabolic Pathways.大黄水提取物通过调节肠道细菌和代谢途径预防缺血性中风。
Metabolites. 2024 Apr 12;14(4):216. doi: 10.3390/metabo14040216.
2
Study on the mechanism of acute liver injury protection in Rhubarb anthraquinone by metabolomics based on UPLC-Q-TOF-MS.基于超高效液相色谱-四极杆飞行时间质谱代谢组学的大黄蒽醌对急性肝损伤保护机制的研究
Front Pharmacol. 2023 Mar 6;14:1141147. doi: 10.3389/fphar.2023.1141147. eCollection 2023.
3
Integrated dose-response metabolomics with therapeutic effects and adverse reactions may demystify the dosage of traditional Chinese medicine.

本文引用的文献

1
Metabolomics Coupled with Multivariate Data and Pathway Analysis on Potential Biomarkers in Cholestasis and Intervention Effect of Paeonia lactiflora Pall.代谢组学结合多变量数据及通路分析用于胆汁淤积潜在生物标志物及白芍干预作用研究
Front Pharmacol. 2016 Feb 4;7:14. doi: 10.3389/fphar.2016.00014. eCollection 2016.
2
Serum Metabolomic Profiling in a Rat Model Reveals Protective Function of Paeoniflorin Against ANIT Induced Cholestasis.大鼠模型中的血清代谢组学分析揭示了芍药苷对ANIT诱导的胆汁淤积的保护作用。
Phytother Res. 2016 Apr;30(4):654-62. doi: 10.1002/ptr.5575. Epub 2016 Jan 25.
3
An experimental study on providing a scientific evidence for seven-time alcohol-steaming of Rhei Rhizoma when clinically used.
将剂量反应代谢组学与治疗效果及不良反应相结合，可能会揭开中药剂量的神秘面纱。
Chin Med. 2022 Nov 19;17(1):130. doi: 10.1186/s13020-022-00687-4.
4
Placenta-Targeted Nanoparticles Loaded with PFKFB3 Overexpression Plasmids Enhance Angiogenesis and Placental Function.负载PFKFB3过表达质粒的胎盘靶向纳米颗粒增强血管生成和胎盘功能。
Bioengineering (Basel). 2022 Nov 4;9(11):652. doi: 10.3390/bioengineering9110652.
5
Chemical and genetic discrimination of commercial Guangchenpi ( 'Chachi') by using UPLC-QTOF-MS/MS based metabolomics and DNA barcoding approaches.基于超高效液相色谱-四极杆飞行时间串联质谱代谢组学和DNA条形码技术对市售广陈皮（“茶枝柑”）进行化学和基因鉴别
RSC Adv. 2019 Jul 29;9(40):23373-23381. doi: 10.1039/c9ra03740c. eCollection 2019 Jul 23.
6
Fuzzy identification of bioactive components for different efficacies of rhubarb by the back propagation neural network association analysis of UPLC-Q-TOF/MS and integrated effects.基于超高效液相色谱-四极杆飞行时间质谱联用技术（UPLC-Q-TOF/MS）的反向传播神经网络关联分析及综合效应实现大黄不同功效生物活性成分的模糊识别
Chin Med. 2022 Apr 26;17(1):50. doi: 10.1186/s13020-022-00612-9.
7
Predicting Target Genes of San-Huang-Chai-Zhu Formula in Treating ANIT-Induced Acute Intrahepatic Cholestasis Rat Model via Bioinformatics Analysis Combined with Experimental Validation.通过生物信息学分析结合实验验证预测三黄柴术方治疗ANIT诱导的急性肝内胆汁淤积大鼠模型的靶基因
Evid Based Complement Alternat Med. 2021 Sep 1;2021:5320445. doi: 10.1155/2021/5320445. eCollection 2021.
8
Study on Hepatotoxicity of Rhubarb Based on Metabolomics and Network Pharmacology.基于代谢组学和网络药理学的大黄肝毒性研究。
Drug Des Devel Ther. 2021 May 4;15:1883-1902. doi: 10.2147/DDDT.S301417. eCollection 2021.
9
Screening for Susceptibility-Related Factors and Biomarkers of Xianling Gubao Capsule-Induced Liver Injury.仙灵骨葆胶囊致肝损伤易感性相关因素及生物标志物的筛查
Front Pharmacol. 2020 May 29;11:810. doi: 10.3389/fphar.2020.00810. eCollection 2020.
10
Metabolomic and Lipidomic Biomarkers for Premalignant Liver Disease Diagnosis and Therapy.用于癌前肝病诊断和治疗的代谢组学和脂质组学生物标志物
Metabolites. 2020 Jan 28;10(2):50. doi: 10.3390/metabo10020050.
一项关于为大黄临床应用时七次酒蒸提供科学依据的实验研究。
BMC Complement Altern Med. 2015 Oct 27;15:388. doi: 10.1186/s12906-015-0922-y.
4
Metabolomics insights into chronic kidney disease and modulatory effect of rhubarb against tubulointerstitial fibrosis.代谢组学对慢性肾脏病的见解及大黄对肾小管间质纤维化的调节作用
Sci Rep. 2015 Sep 28;5:14472. doi: 10.1038/srep14472.
5
Metabolomics changes in a rat model of obstructive jaundice: mapping to metabolism of amino acids, carbohydrates and lipids as well as oxidative stress.阻塞性黄疸大鼠模型中的代谢组学变化：与氨基酸、碳水化合物和脂质代谢以及氧化应激的关联
J Clin Biochem Nutr. 2015 Jul;57(1):50-9. doi: 10.3164/jcbn.14-147. Epub 2015 Jun 4.
6
New paradigms in the treatment of hepatic cholestasis: from UDCA to FXR, PXR and beyond.治疗肝内胆汁淤积的新范式：从 UDCA 到 FXR、PXR 及其他。
J Hepatol. 2015 Apr;62(1 Suppl):S25-37. doi: 10.1016/j.jhep.2015.02.023.
7
MetaboAnalyst 3.0--making metabolomics more meaningful.MetaboAnalyst 3.0——让代谢组学更具意义。
Nucleic Acids Res. 2015 Jul 1;43(W1):W251-7. doi: 10.1093/nar/gkv380. Epub 2015 Apr 20.
8
Metabolomic identification of biochemical changes induced by fluoxetine and imipramine in a chronic mild stress mouse model of depression.在慢性轻度应激抑郁症小鼠模型中，对氟西汀和丙咪嗪诱导的生化变化进行代谢组学鉴定。
Sci Rep. 2015 Mar 9;5:8890. doi: 10.1038/srep08890.
9
Fibrates and cholestasis.贝特类药物与胆汁淤积
Hepatology. 2015 Aug;62(2):635-43. doi: 10.1002/hep.27744. Epub 2015 Mar 23.
10
Bile acid-induced necrosis in primary human hepatocytes and in patients with obstructive cholestasis.胆汁酸诱导的原代人肝细胞坏死及梗阻性胆汁淤积患者的肝细胞坏死
Toxicol Appl Pharmacol. 2015 Mar 15;283(3):168-77. doi: 10.1016/j.taap.2015.01.015. Epub 2015 Jan 28.