Evidence map›Paper›PMID 26965985›Full record

ArticleDrug metabolism and disposition: the biological fate of chemicals2016

Glycyrrhizin Protects against Acetaminophen-Induced Acute Liver Injury via Alleviating Tumor Necrosis Factor α-Mediated Apoptosis.

Tingting Yan, Hong Wang, Min Zhao, Tomoki Yagai, Yingying Chai, Kristopher W Krausz, Cen Xie, Xuefang Cheng, Jun Zhang, Yuan Che and 6 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Drug metabolism and disposition: the biological fate of chemicals, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
7.7field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

32 citing papers in PubMed, 66 citations in OpenAlex.

  1. Review
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  9. Crosstalk between CYP2E1 and PPARActa pharmaceutica Sinica. B · 2022
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  10. Roles of Cofactors in Drug-Induced Liver Injury: Drug Metabolism and Beyond.Drug metabolism and disposition: the biological fate of chemicals · 2022
    Review
  11. Withaferin A alleviates ethanol-induced liver injury by inhibiting hepatic lipogenesis.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2022
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  12. Article
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  15. Review
  16. FXR-Deoxycholic Acid-TNF-α Axis Modulates Acetaminophen-Induced Hepatotoxicity.Toxicological sciences : an official journal of the Society of Toxicology · 2021
    Article
  17. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 5 institutions in 2 countries.

Tingting YanState Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, Jiangsu, People's Republic of China (Ti.Y., H.W., M.Z., Yi.C., X.C., J.Z., Yu.C., F.L., Y.W., G.W., H.H.); Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (Ti.Y., To.Y., K.W.K., C.X., C.N.B., F.J.G.).
Hong WangState Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, Jiangsu, People's Republic of China (Ti.Y., H.W., M.Z., Yi.C., X.C., J.Z., Yu.C., F.L., Y.W., G.W., H.H.); Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (Ti.Y., To.Y., K.W.K., C.X., C.N.B., F.J.G.).
Min ZhaoState Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, Jiangsu, People's Republic of China (Ti.Y., H.W., M.Z., Yi.C., X.C., J.Z., Yu.C., F.L., Y.W., G.W., H.H.); Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (Ti.Y., To.Y., K.W.K., C.X., C.N.B., F.J.G.).
Tomoki YagaiState Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, Jiangsu, People's Republic of China (Ti.Y., H.W., M.Z., Yi.C., X.C., J.Z., Yu.C., F.L., Y.W., G.W., H.H.); Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (Ti.Y., To.Y., K.W.K., C.X., C.N.B., F.J.G.).
Yingying ChaiState Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, Jiangsu, People's Republic of China (Ti.Y., H.W., M.Z., Yi.C., X.C., J.Z., Yu.C., F.L., Y.W., G.W., H.H.); Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (Ti.Y., To.Y., K.W.K., C.X., C.N.B., F.J.G.).
Kristopher W KrauszState Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, Jiangsu, People's Republic of China (Ti.Y., H.W., M.Z., Yi.C., X.C., J.Z., Yu.C., F.L., Y.W., G.W., H.H.); Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (Ti.Y., To.Y., K.W.K., C.X., C.N.B., F.J.G.).
Cen XieState Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, Jiangsu, People's Republic of China (Ti.Y., H.W., M.Z., Yi.C., X.C., J.Z., Yu.C., F.L., Y.W., G.W., H.H.); Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (Ti.Y., To.Y., K.W.K., C.X., C.N.B., F.J.G.).
Xuefang ChengState Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, Jiangsu, People's Republic of China (Ti.Y., H.W., M.Z., Yi.C., X.C., J.Z., Yu.C., F.L., Y.W., G.W., H.H.); Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (Ti.Y., To.Y., K.W.K., C.X., C.N.B., F.J.G.).
Jun ZhangState Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, Jiangsu, People's Republic of China (Ti.Y., H.W., M.Z., Yi.C., X.C., J.Z., Yu.C., F.L., Y.W., G.W., H.H.); Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (Ti.Y., To.Y., K.W.K., C.X., C.N.B., F.J.G.).
Yuan CheState Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, Jiangsu, People's Republic of China (Ti.Y., H.W., M.Z., Yi.C., X.C., J.Z., Yu.C., F.L., Y.W., G.W., H.H.); Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (Ti.Y., To.Y., K.W.K., C.X., C.N.B., F.J.G.).
Feiyan LiState Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, Jiangsu, People's Republic of China (Ti.Y., H.W., M.Z., Yi.C., X.C., J.Z., Yu.C., F.L., Y.W., G.W., H.H.); Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (Ti.Y., To.Y., K.W.K., C.X., C.N.B., F.J.G.).
Yuzheng WuState Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, Jiangsu, People's Republic of China (Ti.Y., H.W., M.Z., Yi.C., X.C., J.Z., Yu.C., F.L., Y.W., G.W., H.H.); Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (Ti.Y., To.Y., K.W.K., C.X., C.N.B., F.J.G.).
Chad N BrockerState Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, Jiangsu, People's Republic of China (Ti.Y., H.W., M.Z., Yi.C., X.C., J.Z., Yu.C., F.L., Y.W., G.W., H.H.); Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (Ti.Y., To.Y., K.W.K., C.X., C.N.B., F.J.G.).
Frank J GonzalezState Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, Jiangsu, People's Republic of China (Ti.Y., H.W., M.Z., Yi.C., X.C., J.Z., Yu.C., F.L., Y.W., G.W., H.H.); Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (Ti.Y., To.Y., K.W.K., C.X., C.N.B., F.J.G.).
Guangji WangState Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, Jiangsu, People's Republic of China (Ti.Y., H.W., M.Z., Yi.C., X.C., J.Z., Yu.C., F.L., Y.W., G.W., H.H.); Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (Ti.Y., To.Y., K.W.K., C.X., C.N.B., F.J.G.) guangjiwang@hotmail.com haipinghao@cpu.edu.cn.
Haiping HaoState Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, Jiangsu, People's Republic of China (Ti.Y., H.W., M.Z., Yi.C., X.C., J.Z., Yu.C., F.L., Y.W., G.W., H.H.); Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (Ti.Y., To.Y., K.W.K., C.X., C.N.B., F.J.G.) guangjiwang@hotmail.com haipinghao@cpu.edu.cn.
State Key Laboratory of Natural MedicineNational Cancer Institute · USCenter for Cancer Research · USNational Institutes of Health · USChina Pharmaceutical University · CN

Funding

Xenobiotic ReceptorsZIABC005708 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI GONZALEZ, FRANK J · 2009 to 2025
$16.4M
Intramural NIH HHS
6 · The paper itself

Abstract

Acetaminophen (APAP) overdose is the leading cause of drug-induced acute liver failure in Western countries. Glycyrrhizin (GL), a potent hepatoprotective constituent extracted from the traditional Chinese medicine liquorice, has potential clinical use in treating APAP-induced liver failure. The present study determined the hepatoprotective effects and underlying mechanisms of action of GL and its active metabolite glycyrrhetinic acid (GA). Various administration routes and pharmacokinetics-pharmacodynamics analyses were used to differentiate the effects of GL and GA on APAP toxicity in mice. Mice deficient in cytochrome P450 2E1 enzyme (CYP2E1) or receptor interacting protein 3 (RIPK3) and their relative wild-type littermates were subjected to histologic and biochemical analyses to determine the potential mechanisms. Hepatocyte death mediated by tumor necrosis factorα(TNFα)/caspase was analyzed by use of human liver-derived LO2 cells. The pharmacokinetics-pharmacodynamics analysis using various administration routes revealed that GL but not GA potently attenuated APAP-induced liver injury. The protective effect of GL was found only with intraperitoneal and intravenous administration and not with gastric administration. CYP2E1-mediated metabolic activation and RIPK3-mediated necroptosis were unrelated to GL's protective effect. However, GL inhibited hepatocyte apoptosis via interference with TNFα-induced apoptotic hepatocyte death. These results demonstrate that GL rapidly attenuates APAP-induced liver injury by directly inhibiting TNFα-induced hepatocyte apoptosis. The protective effect against APAP-induced liver toxicity by GL in mice suggests the therapeutic potential of GL for the treatment of APAP overdose.

Indexed as

AcetaminophenActivation, MetabolicAnimalsApoptosisCell LineChemical and Drug Induced Liver InjuryCytochrome P-450 CYP2E1Glycyrrhizic AcidHepatocytesHumansLiverMaleMiceMice, Inbred C57BLMitochondria, LiverProtective AgentsAcetaminophenCytochrome P-450 CYP2E1Glycyrrhizic AcidProtective AgentsReceptor-Interacting Protein Serine-Threonine KinasesTumor Necrosis Factor-alpha

Identifiers

PMID26965985
PMCPMC4851304
OpenAlexW2325672943

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.