ArticleFrontiers in pharmacology2016
Untargeted Metabolomics Reveals Dose-Response Characteristics for Effect of Rhubarb in a Rat Model of Cholestasis.
Article in Frontiers in pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 37 citations in OpenAlex.
- Berberine-Mediated BCRP Inhibition Enhances Systemic Exposure of Rhein: A Study to Unravel the Pharmacokinetic Basis of Synergy in Da-Huang-Xiao-Shi Decoction.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Rhubarb as a Potential Component of an Anti-Inflammatory Diet.Foods (Basel, Switzerland) · 2025Review
- The Water Extract of Rhubarb Prevents Ischemic Stroke by Regulating Gut Bacteria and Metabolic Pathways.Metabolites · 2024Article
- Study on the mechanism of acute liver injury protection in Rhubarb anthraquinone by metabolomics based on UPLC-Q-TOF-MS.Frontiers in pharmacology · 2023Article
- Integrated dose-response metabolomics with therapeutic effects and adverse reactions may demystify the dosage of traditional Chinese medicine.Chinese medicine · 2022Article
- Placenta-Targeted Nanoparticles Loaded with PFKFB3 Overexpression Plasmids Enhance Angiogenesis and Placental Function.Bioengineering (Basel, Switzerland) · 2022Article
- Fuzzy identification of bioactive components for different efficacies of rhubarb by the back propagation neural network association analysis of UPLC-Q-TOF/MSChinese medicine · 2022Article
- Study on Hepatotoxicity of Rhubarb Based on Metabolomics and Network Pharmacology.Drug design, development and therapy · 2021Article
- 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.Evidence-based complementary and alternative medicine : eCAM · 2021Article
- Metabolomic and Lipidomic Biomarkers for Premalignant Liver Disease Diagnosis and Therapy.Metabolites · 2020Review
- Screening for Susceptibility-Related Factors and Biomarkers of Xianling Gubao Capsule-Induced Liver Injury.Frontiers in pharmacology · 2020Article
- Chemical and genetic discrimination of commercial Guangchenpi (RSC advances · 2019Article
- Integrated Metabolomics and Network Pharmacology Study on Immunoregulation Mechanisms ofEvidence-based complementary and alternative medicine : eCAM · 2019Article
- Identification of potential biomarkers in cholestasis and the therapeutic effect of melatonin by metabolomics, multivariate data and pathway analyses.International journal of molecular medicine · 2018Article
- Bioinformatic and Metabolomic Analysis Reveal Intervention Effects of Chicory in a Quail Model of Hyperuricemia.Evidence-based complementary and alternative medicine : eCAM · 2018Article
- Investigation of Liver Injury ofFrontiers in pharmacology · 2017Article
- Global Metabolomics Reveals the Metabolic Dysfunction in Ox-LDL Induced Macrophage-Derived Foam Cells.Frontiers in pharmacology · 2017Article
- San-Huang-Xie-Xin-Tang Constituents Exert Drug-Drug Interaction of Mutual Reinforcement at Both Pharmacodynamics and Pharmacokinetic Level: A Review.Frontiers in pharmacology · 2016Review
- Metabolomic Study on Idiosyncratic Liver Injury Induced by Different Extracts ofFrontiers in pharmacology · 2016Article
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Authors and funding
18 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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.
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