CoChat
Sign Up
Cited by 29Drug-Induced Hepatotoxicity and ProtectionPlant Toxicity and Pharmacological PropertiesMedicinal plant effects and applications

The DOI matches its Crossref record.

Protective effects of goldenseal (Hydrastis canadensis L.) on acetaminophen-induced hepatotoxicity through inhibition of CYP2E1 in rats

Open access
Yamaura, Katsunori, Nakayama, Noriyuki, Shimada, Maki, Ueno, Koichi·2011·Pharmacognosy Research
DOI 10.4103/0974-8490.89745PMC PMC3249784
Open this paper in CoChat — free account

Abstract

BACKGROUND: Goldenseal (Hydrastis canadensis L.) inhibits various cytochrome P450 (CYP) isoforms such as CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A in vitro. High doses of acetaminophen (APAP) generate the highly reactive intermediate, N-acetyl-p-benzoquinone imine (NAPQI), catalyzed mainly by CYP2E1. The aim of this study was to investigate the hepatoprotective effects of orally administrated goldenseal against APAP-induced acute liver failure (ALF) via inhibition of CYP2E1. MATERIALS AND METHODS: Male Wistar rats were treated orally with goldenseal (300 and 1000 mg/kg) 2, 18, and 26 h before and 6 h after oral APAP (400 mg/kg) administration. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities as well as serum APAP concentration were evaluated. RESULTS: Goldenseal extract inhibited CYP1A2, CYP2D6, CYP2E1, and CYP3A activity, and the inhibitory effect on CYP2E1 was the strongest (IC(50) 4.32 μg/mL). Treatment with goldenseal (300 mg/kg) significantly attenuated the APAP-induced increase in serum AST and ALT, and the hepatoprotective effect of goldenseal was stronger than that of silymarin (200 mg/kg). Moreover, serum APAP concentration was increased by goldenseal treatment, presumably as a result of the inhibitory effect of goldenseal on the metabolism of APAP to NAPQI. CONCLUSION: These results suggest that goldenseal ameliorates APAP-induced ALF and that this protection can likely be attributed to the inhibition of CYP2E1 activity, which generates the highly reactive intermediate of APAP.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.4103/0974-8490.89745

Cites

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The results of the present study are in agreement with previous studies; treatment of paracetamol caused depletion of GSH, cell damage (MDA levels) and mitochondrial dysfunction.

    “The results of present study are in agreement with previous studies; we found that treatment of paracetamol caused depletion of GSH, cell damage (MDA levels) and mitochondrial dysfunction. 4,7,38”

    From Caralluma umbellata Haw. protects liver against paracetamol toxicity and inhibits CYP2E1 (2017) · cites this paper as [7]

    The Results section ('Effects on serum AST and ALT activities'; page not provided) reports increased liver-injury markers after acetaminophen administration in rats, supporting the general claim of liver damage. The paper does not report GSH depletion, MDA levels, or mitochondrial dysfunction; searches for those terms found no supporting passage. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

No references could be resolved yet.

Research works printed but not linked: 25

  1. [1]Black M Acetaminophen hepatotoxicity Annu Rev Med 1984 35 577 93 6372672
  2. [2]Hinson JA Reactive metabolites of phenacetin and acetaminophen: A review Environ Health Perspect 1983 49 71 9 6339229 PMC1569121
  3. [3]Prescott LF Roscoe P Wright N Brown SS Plasmaparacetamol halflife and hepatic necrosis in patients with paracetamol overdosage Lancet 1971 1 519 22 4100436
  4. [4]Lee WM Squires RH Jr Nyberg SL Doo E Hoofnagle JH Acute liver failure: Summary of a workshop Hepatology 2008 47 1401 15 18318440 PMC3381946
  5. [5]Larsen FS Kirkegaard P Rasmussen A Hansen BA The Danish liver transplantation program and patients with serious acetaminophen intoxication Transplant Proc 1995 27 3519 20 8540079
  6. [6]Larson AM Polson J Fontana RJ Davern TJ Lalani E Hynan LS Acetaminophen-induced acute liver failure: Results of a United States multicenter, prospective study Hepatology 2005 42 1364 72 16317692
  7. [7]Tindle HA Davis RB Phillips RS Eisenberg DM Trends in use of complementary and alternative medicine by US adults: 1997-2002 Altern Ther Health Med 2005 11 42 9 15712765
  8. [8]Budzinski JW Foster BC Vandenhoek S Arnason JT An in vitro evaluation of human cytochrome P450 3A4 inhibition by selected commercial herbal extracts and tinctures Phytomedicine 2000 7 273 82 10969720
  9. [9]Foster BC Vandenhoek S Hana J Krantis A Akhtar MH Bryan M In vitro inhibition of human cytochrome P450-mediated metabolism of marker substrates by natural products Phytomedicine 2003 10 334 42 12809364
  10. [10]Chatterjee P Franklin MR Human cytochrome p450 inhibition and metabolic-intermediate complex formation by goldenseal extract and its methylenedioxyphenyl components Drug Metab Dispos 2003 31 1391 7 14570772
  11. [11]Gurley BJ Swain A Hubbard MA Williams DK Barone G Hartsfield F Clinical assessment of CYP2D6-mediated herb-drug interactions in humans: Effects of milk thistle, black cohosh, goldenseal, kava kava, St.John's wort, and Echinacea Mol Nutr Food Res 2008 52 755 63 18214849 PMC2562884
  12. [12]Raner GM Cornelious S Moulick K Wang Y Mortenson A Cech NB Effects of herbal products and their constituents on human cytochrome P450(2E1) activity Food Chem Toxicol 2007 45 2359 65 17658211 PMC2955861
  13. [13]Shayiq RM Roberts DW Rothstein K Snawder JE Benson W Ma X Repeat exposure to incremental doses of acetaminophen provides protection against acetaminophen-induced lethality in mice: An explanation for high acetaminophen dosage in humans without hepatic injury Hepatology 1999 29 451 63 9918922
  14. [14]Castillo T Koop DR Kamimura S Triadafilopoulos G Tsukamoto H Role of cytochrome P-450 2E1 in ethanol-, carbon tetrachloride- and iron-dependent microsomal lipid peroxidation Hepatology 1992 16 992 6 1398507
  15. [15]Lee SS Buters JT Pineau T Fernandez-Salguero P Gonzalez FJ Role of CYP2E1 in the hepatotoxicity of acetaminophen J Biol Chem 1996 271 12063 7 8662637
  16. [16]Raucy JL Lasker JM Lieber CS Black M Acetaminophen activation by human liver cytochromes P450IIE1 and P450IA2 Arch Biochem Biophys 1989 271 270 83 2729995
  17. [17]Thummel KE Lee CA Kunze KL Nelson SD Slattery JT Oxidation of acetaminophen to N-acetyl-p-aminobenzoquinone imine by human CYP3A4 Biochem Pharmacol 1993 45 1563 9 8387297
  18. [18]Dong H Haining RL Thummel KE Rettie AE Nelson SD Involvement of human cytochrome P450 2D6 in the bioactivation of acetaminophen Drug Metab Dispos 2000 28 1397 400 11095574
  19. [19]Patten CJ Thomas PE Guy RL Lee M Gonzalez FJ Guengerich FP Cytochrome P450 enzymes involved in acetaminophen activation by rat and human liver microsomes and their kinetics Chem Res Toxicol 1993 6 511 8 8374050
  20. [20]Smilkstein MJ Bronstein AC Linden C Augenstein WL Kulig KW Rumack BH Acetaminophen overdose: A 48-hour intravenous N-acetylcysteine treatment protocol Ann Emerg Med 1991 20 1058 63 1928874
  21. [21]Pradhan SC Girish C Hepatoprotective herbal drug, silymarin from experimental pharmacology to clinical medicine Indian J Med Res 2006 124 491 504 17213517
  22. [22]Zuber R Modrianský M Dvorák Z Rohovský P Ulrichová J Simánek V Effect of silybin and its congeners on human liver microsomal cytochrome P450 activities Phytother Res 2002 16 632 8 12410543
  23. [23]Masubuchi Y Sugiyama S Horie T Th1/Th2 cytokine balance as a determinant of acetaminophen-induced liver injury Chem Biol Interact 2009 179 273 9 19014921
  24. [24]Rehman J Dillow JM Carter SM Chou J Le B Maisel AS Increased production of antigen-specific immunoglobulins G and M following in vivo treatment with the medicinal plants Echinacea angustifolia and Hydrastis canadensis Immunol Lett 1999 68 391 5 10424448
  25. [25]National Toxicology Program Toxicology and carcinogenesis studies of goldenseal root powder (Hydrastis Canadensis) in F344/N rats and B6C3F1 mice (feed studies) Natl Toxicol Program Tech Rep Ser 2010 562 1 188 21372858

Cited by

Sorted by citations

Metadata

Authors
Yamaura, K., Nakayama, N., Shimada, M., & Ueno, K.
Affiliations
Chiba University (JP)
Corresponding author
Yamaura, Katsunori
ORCID
Shimada, Maki
Venue
Pharmacognosy Research
Publisher
Manuscript Technomedia LLP
Published
2011
Volume
3
Issue
4
Pages
250
ISSN
0974-8490 (ISSN-L)
DOI
10.4103/0974-8490.89745
PMC
PMC3249784
OpenAlex
W2023153930
Cited by
29
References
0
Citations by year
2026: 1 · 2025: 1 · 2024: 2 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 4 · 2019: 1 · 2018: 1 · 2017: 2 · 2016: 2 · 2015: 2 · 2014: 5 · 2013: 4 · 2012: 1
FWCI
2.17
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Pharmacognosy Research (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Plant Toxicity and Pharmacological Properties
  • Health Sciences › Medicine › Complementary and alternative medicine › Medicinal plant effects and applications
Keywords
goldenseal, Hydrastis canadensis, paracetamol, hepatotoxicity, acute liver failure, CYP2E1 inhibition, cytochrome P450, N-acetyl-p-benzoquinone imine, hepatoprotection, silymarin, drug metabolism, transaminases

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review