Evidence map›Paper›PMID 25217484›Full record

ArticleDrug metabolism and disposition: the biological fate of chemicals2014

Wuzhi tablet (Schisandra Sphenanthera extract) protects against acetaminophen-induced hepatotoxicity by inhibition of CYP-mediated bioactivation and regulation of NRF2-ARE and p53/p21 pathways.

Xiaomei Fan, Yiming Jiang, Ying Wang, Huasen Tan, Hang Zeng, Yongtao Wang, Pan Chen, Aijuan Qu, Frank J Gonzalez, Min Huang and 1 more

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In one paragraph

Article in Drug metabolism and disposition: the biological fate of chemicals, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
9.0field-weighted citation impact, top 2% 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

25 citing papers in PubMed, 61 citations in OpenAlex.

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  4. Acta pharmaceutica Sinica. B · 2023
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  11. Hepatoprotective Effect ofInternational journal of biological sciences · 2020
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  12. Review
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  14. Article
  15. Article
  16. Acta pharmaceutica Sinica. B · 2017
    Article
  17. Article
  18. Schisandrin B attenuates CClDrug design, development and therapy · 2017
    Article
  19. Article
  20. Evidence-based complementary and alternative medicine : eCAM · 2017
    Article
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

11 authors at 5 institutions in 2 countries.

Xiaomei FanSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China (X.F., Y.J., Yo.W., H.T., H.Z., Yi. W., M.H., H.B.); The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China (P.C.); and Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (A.Q., F.J.G).
Yiming JiangSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China (X.F., Y.J., Yo.W., H.T., H.Z., Yi. W., M.H., H.B.); The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China (P.C.); and Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (A.Q., F.J.G).
Ying WangSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China (X.F., Y.J., Yo.W., H.T., H.Z., Yi. W., M.H., H.B.); The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China (P.C.); and Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (A.Q., F.J.G).
Huasen TanSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China (X.F., Y.J., Yo.W., H.T., H.Z., Yi. W., M.H., H.B.); The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China (P.C.); and Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (A.Q., F.J.G).
Hang ZengSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China (X.F., Y.J., Yo.W., H.T., H.Z., Yi. W., M.H., H.B.); The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China (P.C.); and Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (A.Q., F.J.G).
Yongtao WangSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China (X.F., Y.J., Yo.W., H.T., H.Z., Yi. W., M.H., H.B.); The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China (P.C.); and Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (A.Q., F.J.G).
Pan ChenSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China (X.F., Y.J., Yo.W., H.T., H.Z., Yi. W., M.H., H.B.); The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China (P.C.); and Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (A.Q., F.J.G).
Aijuan QuSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China (X.F., Y.J., Yo.W., H.T., H.Z., Yi. W., M.H., H.B.); The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China (P.C.); and Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (A.Q., F.J.G).
Frank J GonzalezSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China (X.F., Y.J., Yo.W., H.T., H.Z., Yi. W., M.H., H.B.); The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China (P.C.); and Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (A.Q., F.J.G).
Min HuangSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China (X.F., Y.J., Yo.W., H.T., H.Z., Yi. W., M.H., H.B.); The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China (P.C.); and Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (A.Q., F.J.G).
Huichang BiSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China (X.F., Y.J., Yo.W., H.T., H.Z., Yi. W., M.H., H.B.); The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China (P.C.); and Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (A.Q., F.J.G) bihchang@mail.sysu.edu.cn.
Center for Cancer Research · USNational Cancer Institute · USNational Institutes of Health · USSun Yat-sen University · CNThe First Affiliated Hospital, Sun Yat-sen University · CN

Funding

Xenobiotic receptorsZIABC005562 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI GONZALEZ, FRANK J · 2009 to 2025
$26.9M
Xenobiotic ReceptorsZIABC005708 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI GONZALEZ, FRANK J · 2009 to 2025
$16.4M
6 · The paper itself

Abstract

Schisandra sphenanthera is widely used as a tonic and restorative in many countries to enhance the function of liver and other organs. Wuzhi tablet (WZ) is a preparation of an ethanol extract of Schisandra sphenanthera. Our previous study demonstrated that WZ exerted a protective effect toward acetaminophen (APAP)-induced hepatotoxicity. However, the molecular mechanisms of this protection remain unclear. This study aimed to determine what molecular pathways contributed to the hepatoprotective effects of WZ against APAP toxicity. Administration of WZ 3 days before APAP treatment significantly attenuated APAP hepatotoxicity in a dose-dependent manner and reduced APAP-induced JNK activation. Treatment with WZ resulted in potent inhibition of CYP2E1, CYP3A11, and CYP1A2 activities and then caused significant inhibition of the formation of the oxidized APAP metabolite N-acetyl-p-benzoquinone imine-reduced glutathione. The expression of NRF2 was increased after APAP and/or WZ treatment, whereas KEAP1 levels were decreased. The protein expression of NRF2 target genes including Gclc, Gclm, Ho-1, and Nqo1 was significantly increased by WZ treatment. Furthermore, APAP increased the levels of p53 and its downstream gene p21 to trigger cell cycle arrest and apoptosis, whereas WZ pretreatment could inhibit p53/p21 signaling to induce cell proliferation-associated proteins including cyclin D1, CDK4, PCNA, and ALR to promote hepatocyte proliferation. This study demonstrated that WZ prevented APAP-induced liver injury by inhibition of cytochrome P450-mediated APAP bioactivation, activation of the NRF2-antioxidant response element pathway to induce detoxification and antioxidation, and regulation of the p53, p21, cyclin D1, CDK4, PCNA, and ALR to facilitate liver regeneration after APAP-induced liver injury.

Indexed as

AcetaminophenAnimalsAntioxidantsCarboxylic Ester HydrolasesCell ProliferationChemical and Drug Induced Liver InjuryCyclin-Dependent Kinase Inhibitor p21Cytochrome P-450 Enzyme SystemDrugs, Chinese HerbalHepatocytesLiverMaleMiceMice, Inbred C57BLNF-E2-Related Factor 2Plant ExtractsAcetaminophenAntioxidantsarylesteraseCarboxylic Ester HydrolasesCyclin-Dependent Kinase Inhibitor p21Cytochrome P-450 Enzyme SystemDrugs, Chinese HerbalNfe2l2 protein, mouseNF-E2-Related Factor 2Plant ExtractsProtective AgentsTabletsTumor Suppressor Protein p53wuzhi

Identifiers

PMID25217484
PMCPMC6067381
OpenAlexW2098659838

What OpenQuestion holds

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Registered trials

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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.