Potato Peel Extract Shows Hepatoprotective Signals in Acetaminophen Toxicity Study

Potato peel, a waste product that most kitchens discard without a second thought, has emerged as the unexpected star of a new preclinical study into acetaminophen liver injury. Researchers report that an ethanolic extract of Solanum tuberosum peel protected liver cells and chicken embryos from the damaging effects of acetaminophen, one of the world’s most widely consumed painkillers, by modulating inflammatory cytokines, apoptotic genes, and the drug-metabolising enzyme CYP3A4. The work, published in the Future Journal of Pharmaceutical Sciences, combines computational docking, human liver cell assays, and an embryonic chicken model, and its authors are careful to stress that the findings remain far from clinical application.

Acetaminophen, also known as paracetamol, sits on the World Health Organisation’s list of essential medicines and is bought over the counter in countless formulations. In India alone, more than 800 products containing the drug are available in doses ranging from 80 to 1000 milligrams. At therapeutic doses the drug is considered safe, but repeated supra-therapeutic ingestion can cause drug-induced liver injury, acute liver injury, and acute liver failure. The estimated overall case fatality rate is around 0.7 percent, a figure the authors note is likely underreported in many countries, and the true prevalence in India is obscured by underdiagnosis and the high background burden of other liver diseases such as non-alcoholic fatty liver disease.

The biochemistry of acetaminophen toxicity hinges on a toxic metabolite. Roughly ten percent of a dose is oxidised, primarily by CYP2E1 and to a lesser extent by CYP1A2 and CYP3A4, into N-acetyl-p-benzoquinone imine, or NAPQI. Under normal dosing, NAPQI is produced in small amounts and rapidly neutralised by conjugation with glutathione. When doses climb, or when risk factors such as alcohol consumption, cytochrome P450 induction, or malnutrition deplete glutathione, the detoxification capacity is overwhelmed. Excess NAPQI binds cellular proteins, drives mitochondrial dysfunction, and triggers reactive oxygen species that activate c-Jun N-terminal kinase, or JNK, ultimately producing oxidative stress, ATP depletion, membrane rupture, and necrotic cell death. N-acetylcysteine remains the only US FDA-approved antidote, but it works best within a narrow therapeutic window and is less beneficial in late-presenting cases.

That gap motivated the search for complementary hepatoprotective strategies. The team screened seventy phytochemicals drawn from plants used in traditional and complementary medicine systems, docking each against the crystal structure of human CYP3A4. Solanine, a steroidal glycoalkaloid abundant in potatoes, posted the strongest docking score at −11.3 kcal/mol, ahead of beta-sitosterol at −10.7 and sarsaponin at −10.6. Potatoes contain more than eighty steroidal glycoalkaloids, with alpha-solanine and alpha-chaconine making up as much as 95 percent of the total in cultivated varieties. In multi-ligand docking, glutathione alone bound CYP3A4 with an affinity of −6.3 kcal/mol, while solanine docked against a pre-formed CYP3A4–glutathione complex retained a strong −11.2 kcal/mol, which the authors interpret as a possible synergistic interaction that could enhance glutathione-dependent detoxification of NAPQI while limiting excessive metabolite formation.

The computational hypothesis was then tested on living cells. The researchers prepared separate ethanolic extracts from potato pulp and peel, defatting the dried material with petroleum ether before maceration in ethanol, and obtained a crude extract yield of 12 percent. In MTT assays on Hep G2 hepatocarcinoma cells, the peel extract showed a distinctly safer profile: at 0.03 µg/mL, roughly 60 percent of cells remained viable for up to 20 hours, whereas the pulp extract left about 80 percent viable only up to 16 hours at the same concentration, with viability dropping to around 38 percent at 0.04 µg/mL. Colony formation assays reinforced the contrast. The pulp extract at 0.03 µg/mL significantly inhibited proliferation, shrinking colonies and disrupting their architecture, while peel-treated cells formed well-defined, densely packed colonies, and the peel extract showed no inhibitory effect on Hep G2 proliferation for up to 96 hours.

Fluorescence imaging added a visual dimension to the safety comparison. Under DAPI staining, untreated control Hep G2 cells displayed normal nuclear architecture, while acetaminophen treatment produced chromatin condensation, nuclear fragmentation, and a pronounced drop in cell number. Cells treated with the peel extract showed near-normal nuclei with substantially reduced cell death, and therapeutic administration of peel after acetaminophen exposure produced the most pronounced recovery, with most cells exhibiting normal nuclear morphology. The pulp extract offered partial mitigation, but residual nuclear alterations remained visible, leading the authors to describe the peel extract as the superior cytoprotective preparation.

The pivotal experiments took place inside embryonated chicken eggs. Fourteen-day-old, pathogen-free fertilised eggs were divided into eight groups, including a blank control, a 70 percent ethanol vehicle control, an acetaminophen-only challenge group, and groups receiving acetaminophen followed by pulp or peel extract, as well as extract-only groups. After 48 hours, allantoic fluid was collected for RT-PCR analysis, and liver, heart, and brain tissue were fixed and examined histologically with haematoxylin-eosin staining.

The molecular readouts were striking. Interleukin-1β and IL-6, both sharply elevated by acetaminophen challenge, fell markedly with either extract, and TGF-β1, released by hepatocytes during acute toxicity, was similarly suppressed. Pro-apoptotic Bax and Caspase-3 expression dropped in the treatment groups, and JNK, the stress kinase central to acetaminophen’s mitochondrial toxicity cascade, was significantly down-regulated. In a paradoxical twist, acetaminophen overdosing significantly down-regulated CYP3A4 expression in the embryos, while the extract-treated challenge groups showed significant up-regulation of the enzyme, a pattern the authors link to restoring CYP-mediated metabolic function. Histopathology corroborated the molecular data: acetaminophen caused massive focal necrosis in brain, gross necrosis and architectural loss in liver, and focal necrosis and myocardial swelling in heart, with the peel extract providing the more effective protection, particularly in liver and heart, while the pulp extract offered minimal cardioprotection.

The authors situate these results within the immunology of drug-induced liver injury, in which necrotic hepatocytes release damage-associated molecular patterns that recruit immune cells, and Kupffer cells secrete TNF-α, IL-6, and IL-1β following acetaminophen challenge. By suppressing pro-inflammatory cytokines and elevating anti-inflammatory signalling, the extract appears to shift the balance toward resolution, and the team suggests that modulation of JNK signalling could have implications beyond acute injury, given the pathway’s involvement in fatty liver disease, steatohepatitis, and hepatocellular carcinoma. They also note that CYP3A4 metabolises roughly 70 percent of therapeutic agents in humans, so any compound that modulates its activity warrants careful scrutiny for drug interactions.

Caution, however, frames the entire enterprise. The chicken embryo model sits between conventional cell culture and mammalian in vivo systems, and its applicability in toxicological research remains comparatively underexplored. The study also lacked quantitative characterisation of solanine or other bioactive constituents by techniques such as HR-LC–MS, HPLC, or LC–MS/MS, and the contribution of CYP3A4 to acetaminophen hepatotoxicity itself remains contested, with some in vivo reports attributing only about 5 to 10 percent of NAPQI formation to the enzyme. The authors explicitly call for well-designed preclinical and clinical studies, direct comparisons with established positive controls, and combination treatment strategies before any therapeutic claims can be made. For now, the message is a measured one: a compound abundant in potato peel shows coherent protective signals across docking, cell, and embryo models, and deserves rigorous follow-up, not a place in the medicine cabinet.

Subject of Research: Hepatoprotective effects of Solanum tuberosum peel extract against acetaminophen-induced liver toxicity in cell and embryonic models

Article Title: Solanum tuberosum peel extract attenuates acetaminophen-induced hepatotoxicity through modulation of inflammatory cytokines, apoptotic pathways, and CYP3A4 expression: evidence from molecular docking, Hep G2 cell assays, and an in ovo embryonic model

Article References: Goswami, P., Chatterjee, D., Fakola, E. G., Roy, A., Paira, K., Ghorai, T., Pan, S., Majumder, A., & Das, S. (2026). Solanum tuberosum peel extract attenuates acetaminophen-induced hepatotoxicity through modulation of inflammatory cytokines, apoptotic pathways, and CYP3A4 expression: evidence from molecular docking, Hep G2 cell assays, and an in ovo embryonic model. Future Journal of Pharmaceutical Sciences, 12(1), Article 95. https://doi.org/10.1186/s43094-026-01028-0

Image Credits: AI Generated

DOI: 10.1186/s43094-026-01028-0

Keywords: acetaminophen, hepatotoxicity, Solanum tuberosum, solanine, CYP3A4, NAPQI, glutathione, JNK, Hep G2 cells, chicken embryo model, molecular docking, cytokines