Drug-induced liver injury and anti-hepatotoxic effect of herbal compounds: a metabolic mechanism perspective
Abstract
Background Drug-induced liver injury (DILI) is the most challenging and thought-provoking liver problem for hepatologists owing to unregulated medication usage in medical practices, nutritional supplements, and botanicals. Due to underreporting, analysis, and identification issues, clinically evaluated medication hepatotoxicity is prevalent yet hard to quantify. Purpose This review's primary objective is to thoroughly compare pharmaceutical drugs and herbal compounds that have undergone clinical trials, focusing on their metabolic mechanisms contributing to the onset of liver illnesses and their hepatoprotective effects. Methods The data was gathered from several online sources, such as PubMed, Scopus, Google Scholar, and Web of Science, using appropriate keywords. Results The prevalence of conventional and herbal medicine is rising. A comprehensive understanding of the metabolic mechanism is necessary to mitigate the hepatotoxicity induced by drugs and facilitate the incorporation or substitution of herbal medicine instead of pharmaceuticals. Moreover, pre-clinical pharmacological research has the potential to facilitate the development of natural products as therapeutic agents, displaying promising possibilities for their eventual clinical implementation. Conclusions Acetaminophen, isoniazid, rifampicin, diclofenac, and pyrogallol have been identified as the most often reported synthetic drugs that produce hepatotoxicity by oxidative stress, inflammation, apoptosis, and fibrosis during the last several decades. Due to their ability to downregulate many factors (such as cytokines) and activate several enzyme/enzyme systems, herbal substances (such as Gingko biloba extract, curcumin, resveratrol, and silymarin) provide superior protection against harmful mechanisms which induce hepatotoxicity with fewer adverse effects than their synthetic counterparts.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
Diclofenac is biotransformed primarily through specific drug-metabolizing enzymes, including members of the CYP family such as CYP2C9 and CYP3A4.
“Previous studies have shown that diclofenac is biotransformed primarily through specific drug-metabolizing enzymes, including members of the CYP family such as CYP2C9 and CYP3A4.”
From Decellularized liver scaffolds for constructing drug-metabolically functional ex vivo human liver models (2025) · cites this paper as [29]
Genetic polymorphisms, drug overdosage, or interactions with other medications can lead to variations in the activity of these enzymes, thereby influencing the metabolic rate of diclofenac and the generation of toxic intermediates, ultimately increasing the risk of liver toxicity.
“Genetic polymorphisms, drug overdosage, or interactions with other medications can lead to variations in the activity of these enzymes, thereby influencing the metabolic rate of diclofenac and the generation of toxic intermediates, ultimately increasing the risk of liver toxicity [28,29].”
From Decellularized liver scaffolds for constructing drug-metabolically functional ex vivo human liver models (2025) · cites this paper as [29]
Cites
Cytochrome P450 Enzymes and Drug Metabolism in Humans
Zhao, M., Ma, J., Li, M., Zhang, Y., Jiang, B., Zhao, X., Huai, C., Shen, L., Zhang, N., He, L., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222312808 · Cited by 1,070 · see citing works
Acetaminophen-Induced Hepatotoxicity: a Comprehensive Update
(2016) · Journal of Clinical and Translational Hepatology · doi:10.14218/jcth.2015.00052 · Cited by 744 · see citing works
Björnsson, H. K., Björnsson, E. S., Avula, B., Khan, I. A., Jonasson, J. G., Ghabril, M., Hayashi, P. H., & Navarro, V. (2020) · Liver International · doi:10.1111/liv.14393 · Cited by 118 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Liu, J., Hanson, A., Yin, W., Wu, Q., Wauthier, E., Diao, J., Dinh, T., Macdonald, J., Li, R., Terajima, M., et al. (2025) · Bioactive Materials · doi:10.1016/j.bioactmat.2024.09.029 · Cited by 9 · see citing works
“Genetic polymorphisms, drug overdosage, or interactions with other medications can lead to variations in the activity of these enzymes, thereby influencing the metabolic rate of diclofenac and the generation of toxic intermediates, ultimately increasing the risk of liver toxicity [28,29].”
Background
- Authors
- Rani, J., Dhull, S. B., Rose, P. K., & Kidwai, M. K.
- Affiliations
- Chaudhary Devi Lal University (IN)
- Corresponding author
- Dhull, Sanju Bala
- Rose, Pawan Kumar
- Venue
- Phytomedicine
- Publisher
- Elsevier BV
- Published
- 2024-01
- Volume
- 122
- Pages
- 155142
- ISSN
- 0944-7113 (ISSN-L)
- OpenAlex
- W4387538709
- Cited by
- 91
- References
- 3
- Citations by year
- 2026: 32 · 2025: 33 · 2024: 26
- FWCI
- 4.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Phytomedicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Plant Toxicity and Pharmacological Properties
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Silymarin and Mushroom Poisoning
- Keywords
- drug-induced liver injury, hepatotoxicity, herbal compounds, hepatoprotection, oxidative stress, inflammation, apoptosis, liver fibrosis, paracetamol, isoniazid, rifampicin, diclofenac, pyrogallol, curcumin, resveratrol, silymarin, natural products, drug metabolism
- MeSH terms
- Isoniazid, Liver, Plant Extracts, Plants, Medicinal, Silymarin, Chemical and Drug Induced Liver Injury
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