# Lactobacillus plantarum-fermented persimmon juice alleviates alcohol-induced hepatic ferroptosis by activating the Keap1/Nrf2 antioxidant axis

**Authors:** Huijuan Kuang, Qingyuan Ye, Juan Tong, Hong Fu, Zhiqiang Shi, Bin Zhu, Guotai Yang

PMC · DOI: 10.3389/fmicb.2026.1679233 · Frontiers in Microbiology · 2026-02-06

## TL;DR

Fermented persimmon juice helps reduce alcohol-related liver damage in mice by boosting antioxidants and reducing harmful cell death.

## Contribution

This study shows that Lactobacillus plantarum-fermented persimmon juice can alleviate alcohol-induced liver injury through the Keap1/Nrf2 antioxidant pathway.

## Key findings

- Fermented persimmon juice improved hepatic lipid metabolism in mice.
- Fermented juice activated the Keap1/Nrf2 pathway and reduced ferroptosis markers.
- Fermented juice contained higher levels of antioxidants like chlorogenic acid.

## Abstract

Alcoholic liver disease (ALD), induced by chronic and excessive alcohol consumption, poses a significant health risk, with higher female susceptibility. This study investigated Lactobacillus plantarum fermented persimmon juice (Fj) against ALD in female C57BL/6 mice.

The model mice were orally treated with Fj or unfermented persimmon juice (Pj). The bioactive compound profiles of Fj and Pj were detected by HPLC-MS. The hepatoprotective effects was evaluated through assessments of hepatic lipid metabolism, Keap1/Nrf2 pathway proteins, and ferroptosis markers.

HPLC-MS analysis confirmed Fj was enriched in bioactive compounds including elevated antioxidants such as chlorogenic acid and p-hydrobenzoic acid. Daily Fj administration (10 μg/g BW) significantly improved hepatic lipid metabolism and regulated Keap1/Nrf2 signaling pathway, ultimately mitigating hepatic ferroptosis.

These findings demonstrate that probiotic fermentation as a strategic approach to develop postbiotic-based functional beverages for mitigating alcohol-induced liver injury, offering translational potential against ALD progression.

## Linked entities

- **Genes:** KEAP1 (kelch like ECH associated protein 1) [NCBI Gene 9817], GABPA (GA binding protein transcription factor subunit alpha) [NCBI Gene 2551]
- **Chemicals:** chlorogenic acid (PubChem CID 1794427)
- **Diseases:** alcoholic liver disease (MONDO:0043693), ALD (MONDO:0010247)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Actb (actin, beta) [NCBI Gene 11461] {aka Actx, E430023M04Rik, beta-actin}, Nfe2l2 (nuclear factor, erythroid derived 2, like 2) [NCBI Gene 18024] {aka Nrf2}, Ftl1 (ferritin light polypeptide 1) [NCBI Gene 14325] {aka Ftl, Ftl-1, L-ferritin}, Cat (catalase) [NCBI Gene 12359] {aka 2210418N07, Cas-1, Cas1, Cs-1}, Keap1 (kelch-like ECH-associated protein 1) [NCBI Gene 50868] {aka INRF2, mKIAA0132}, Gpt (glutamic pyruvic transaminase, soluble) [NCBI Gene 76282] {aka 1300007J06Rik, 2310022B03Rik, ALT, ALT1, Gpt-1, Gpt1}, Ppara (peroxisome proliferator activated receptor alpha) [NCBI Gene 19013] {aka 4933429D07Rik, Nr1c1, PPAR-alpha, PPARalpha, Ppar}, Acsl4 (acyl-CoA synthetase long-chain family member 4) [NCBI Gene 50790] {aka 9430020A05Rik, ACS4, Facl4, Lacs4}, Slc17a5 (solute carrier family 17 (anion/sugar transporter), member 5) [NCBI Gene 235504] {aka 4631416G20Rik, 4732491M05, AST, ISSD, NSD, SD}, KEAP1 (kelch like ECH associated protein 1) [NCBI Gene 9817] {aka INrf2, KLHL19}, Gpx4 (glutathione peroxidase 4) [NCBI Gene 625249] {aka GPx-4, GSHPx-4, PHGPx, mtPHGPx, snGPx}, Fth1 (ferritin heavy polypeptide 1) [NCBI Gene 14319] {aka FHC, Fth, HFt, MFH}, Nox1 (NADPH oxidase 1) [NCBI Gene 237038] {aka GP91-2, MOX1, NOH-1, NOH1, NOX1a, NOX1alpha}, NFE2L2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 4780] {aka IMDDHH, NRF2, Nrf-2}
- **Diseases:** alcoholic fatty liver (MESH:D005235), Alcoholic liver steatosis (MESH:D005234), iron (MESH:D000090463), Alcohol Abuse and Alcoholism (MESH:D000437), iron overload (MESH:D019190), cirrhosis (MESH:D005355), liver disease (MESH:D008107), inflammation (MESH:D007249), liver injury (MESH:D017093), hepatic cellular (MESH:D056486), hypertrophic (MESH:D002312), adiposity (MESH:D018205), depression (MESH:D003866), ALD (MESH:D008108), necrosis (MESH:D009336), dislocation (MESH:D004204), hepatocellular carcinoma (MESH:D006528), hepatic lipid metabolic disorders (MESH:D052439), hepatic hypertrophy (MESH:D006984)
- **Chemicals:** Oil red O (MESH:C011049), Iron (MESH:D007501), carotenoids (MESH:D002338), water (MESH:D014867), Ethanol (MESH:D000431), cholesterol (MESH:D002784), vitamin C (MESH:D001205), p-hydroxybenzoic acid (MESH:C038193), o-phenanthroline (MESH:C025205), oxygen (MESH:D010100), DHE (MESH:C067883), formic acid (MESH:C030544), sugar (MESH:D000073893), methanol (MESH:D000432), saline (MESH:D012965), silymarin (MESH:D012838), OCT (MESH:C051883), succinic acid (MESH:D019802), LPO (MESH:D008054), pentobarbital sodium (MESH:D010424), L-tartaric acid (MESH:C029768), TG (MESH:D014280), acetonitrile (MESH:C032159), DPPH (MESH:C004931), L-lactic acid (MESH:D019344), OH (MESH:C031356), Lipid (MESH:D008055), ABTS (MESH:C002502), citric acid (MESH:D019343), GSH (MESH:D005978), polyphenols (MESH:D059808), short-chain fatty acids (MESH:D005232), ROS (MESH:D017382), chlorogenic acid (MESH:D002726), glucose (MESH:D005947), formalin (MESH:D005557), flavonoids (MESH:D005419), HNO3 (MESH:D017942), Alcohol (MESH:D000438), HClO4 (MESH:C576518), eosin (MESH:D004801), Hematoxylin (MESH:D006416), H&amp;E (MESH:D006371), D-(+) malic acid (-), H2O2 (MESH:D006861), K2S2O8 (MESH:C009007), flavonolignan (MESH:D044947), carbohydrates (MESH:D002241), MDA (MESH:D008315), fatty acid (MESH:D005227), tannins (MESH:D013634), amino acids (MESH:D000596), peroxides (MESH:D010545)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Lactiplantibacillus plantarum (species) [taxon 1590], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** /6 — Homo sapiens (Human), Tongue squamous cell carcinoma, Cancer cell line (CVCL_5985)

## Full text

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## Figures

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## References

50 references — full list in the complete paper: https://tomesphere.com/paper/PMC12920458/full.md

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Source: https://tomesphere.com/paper/PMC12920458