Hepatoprotective effects of gamma-aminobutyric acid-enriched fermented Hovenia dulcis extract on ethanol-induced liver injury in mice
Open accessAbstract
Abstract Background Various extracts of Hovenia dulcis have been commonly used in Asia for cases of alcohol-related disorders. Fermentation is reported to enhance the level and biological activities of various bio-constituents of plant extracts. Therefore, this study was undertaken to evaluate the effects of fermented H. dulcis extract (FHDE) on ethanol-induced liver injury in mice. Methods FHDE was prepared using Bacillus subtilis and Lactobacillus plantarum. The effects of FHDE on ethanol-induced liver injury were evaluated in C57BL/6 N CrSlc mice. A mixed feed preparation containing the fermented extract with and without ethanol was given to mice for 29 days, according to its group. At the end of the experiment, blood and liver samples were collected from all mice in the group. Plasma biochemical analysis and histopathological investigation were performed to evaluate the impacts of treatment on the biomarkers of hepatic damage and inflammatory changes. Besides, the expression of genes that regulate the activities of enzymes associated with alcohol metabolism, antioxidant activity, and fatty acid oxidation was assessed using a quantitative real-time polymerase chain reaction. Moreover, the amino acid contents and the active ingredients of the extract were evaluated before and after fermentation. Results Fermentation resulted in a marked increase and decrease in the amount of Gamma-Amino-n-butyric acid (GABA) and glutamic acid, respectively. FHDE enhanced the body weight gain of mice compared to ethanol. Besides, plasma levels of triglyceride, low-density lipoprotein, the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were significantly (P < 0.05) reduced in the FHDE-treated groups relative to the ethanol-treated control. FHDE upregulated the expression of genes associated with enzymes involved in alcohol dehydrogenation (Adh1 and Aldh2), antioxidant activity (SOD and CAT), and fatty acid oxidation (PPAR-α and PGC-1α). However, the expressions of Cytochrome peroxidase Cyp2E1 and genes related to lipogenesis (SREBP-1c, FAS, SCD-1, and ACC) were significantly (P < 0.05) downregulated following treatment with the FHDE. Histopathological investigation demonstrated a slight degree of inflammatory cell infiltration and occasional fatty changes in the FHDE-treated groups. Conclusion The GABA-enriched fermented H. dulcis extract prevented ethanol-induced hepatic damage by enhancing the antioxidant defense system, fatty acid oxidation, and reducing lipogenesis.
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.
Integrity signals
Registry
Cites
Statistics
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.
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?
GABA-rich fermented extracts and oolong tea have been shown to lower plasma triglyceride and low-density lipoprotein levels, down-regulate genes related to adipogenesis (SREBP-1c, FAS, SCD-1, and ACC), and promote lipid metabolism and fatty acid oxidation.
“Furthermore, GABA-rich fermented extracts and oolong tea have been shown to lower plasma triglyceride and low-density lipoprotein levels, down-regulate genes related to adipogenesis (SREBP-1c, FAS, SCD-1, and ACC), and promote lipid metabolism and fatty acid oxidation (Park et al., 2020; Weerawatanakorn et al., 2023).”
From Lactiplantibacillus plantarum N4 ameliorates lipid metabolism and gut microbiota structure in high fat diet-fed rats (2024) · cites this paper as Park et al., 2020
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Role of AMP-Activated Protein Kinase in Mechanism of Metformin Action
Zhou, G., Myers, R., Li, Y., Chen, Y., Shen, X., Fenyk-Melody, J., Wu, M., Ventre, J., Doebber, T., Fujii, N., et al. (2001) · Journal of Clinical Investigation · doi:10.1172/jci13505 · Cited by 5,652 · see citing works
Interactions Between the Intestinal Microbiome and Liver Diseases
Schnabl, B., & Brenner, D. A. (2014) · Gastroenterology · doi:10.1053/j.gastro.2014.01.020 · Cited by 971 · see citing works
Bioactive phenolic compounds: Production and extraction by solid-state fermentation. A review
Martins, S., Mussatto, S. I., Martínez-Ávila, G. C. G., Montañez, J., Aguilar, C. N., & Teixeira, J. A. (2011) · Biotechnology Advances · doi:10.1016/j.biotechadv.2011.01.008 · Cited by 737 · see citing works
Alcoholic fatty liver: its pathogenesis and mechanism of progression to inflammation and fibrosis
Lieber, C. S. (2004) · Alcohol · doi:10.1016/j.alcohol.2004.07.008 · Cited by 699 · see citing works
Cholesterol-Lowering Effects of Probiotics and Prebiotics: A Review of in Vivo and in Vitro Findings
Ooi, L.-G., & Liong, M. (2010) · International Journal of Molecular Sciences · doi:10.3390/ijms11062499 · Cited by 690 · see citing works
Bull–Otterson, L., Feng, W., Kirpich, I., Wang, Y., Qin, X., Liu, Y., Gobejishvili, L., Joshi‐Barve, S., Ayvaz, T., Petrosino, J. F., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0053028 · Cited by 543 · see citing works
Inhibitory role for GABA in autoimmune inflammation
Bhat, R., Axtell, R., Mitra, A., Miranda, M., Lock, C., Tsien, R. W., & Steinman, L. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0915139107 · Cited by 509 · see citing works
The role of GABAA receptors in the acute and chronic effects of ethanol: a decade of progress
Kumar, S., Porcu, P., Werner, D. F., Matthews, D. B., Diaz‐Granados, J. L., Helfand, R. S., & Morrow, A. L. (2009) · Psychopharmacology · doi:10.1007/s00213-009-1562-z · Cited by 432 · see citing works
Woods, A., Azzout‐Marniche, D., Foretz, M., STEIN, S. C., Lemarchand, P., Ferré, P., Foufelle, F., & Carling, D. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.18.6704-6711.2000 · Cited by 404 · see citing works
Review of natural products with hepatoprotective effects
Madrigal‐Santillán, E. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i40.14787 · Cited by 394 · see citing works
Fermentations in World Food Processing
Steinkraus, K. H. (2002) · Comprehensive Reviews in Food Science and Food Safety · doi:10.1111/j.1541-4337.2002.tb00004.x · Cited by 313 · see citing works
Bacterial translocation and changes in the intestinal microbiome in mouse models of liver disease
Fouts, D. E., Torralba, M., Nelson, K. E., Brenner, D. A., & Schnabl, B. (2012) · Journal of Hepatology · doi:10.1016/j.jhep.2012.01.019 · Cited by 311 · see citing works
Lu, Y., Wu, D., Wang, X., Ward, S. C., & Cederbaum, A. I. (2010) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2010.07.026 · Cited by 193 · see citing works
Gut microbiota and probiotics in chronic liver diseases
Cesaro, C., Tiso, A., Del Prete, A., Cariello, R., Tuccillo, C., Cotticelli, G., del Vecchio Blanco, C., & Loguercio, C. (2011) · Digestive and Liver Disease · doi:10.1016/j.dld.2010.10.015 · Cited by 182 · see citing works
Wang, M., Zhu, P., Jiang, C., Ma, L., Zhang, Z., & Zeng, X. (2012) · Food and Chemical Toxicology · doi:10.1016/j.fct.2012.06.034 · Cited by 156 · see citing works
Dong, H., Kumar, M., Zhang, Y., Gyulkhandanyan, A. V., Xiang, Y.-Y., Ye, B., Perrella, J., Hyder, A., Zhang, N., Wheeler, M. B., et al. (2006) · Diabetologia · doi:10.1007/s00125-005-0123-1 · Cited by 117 · see citing works
Alcohol–Induced Liver Injury in Mice Lacking Cu, Zn–Superoxide Dismutase
Kessova, I. G., Ho, Y., Thung, S. N., & Cederbaum, A. I. (2003) · Hepatology · doi:10.1053/jhep.2003.50450 · Cited by 108 · see citing works
Hovenia dulcis– An Asian Traditional Herb
Hyun, T. K., Eom, S. H., Yu, C. M., & Roitsch, T. G. (2010) · Planta Medica · doi:10.1055/s-0030-1249776 · Cited by 107 · see citing works
huang, L.-L., Wan, J., Wang, B., He, C., Ma, H., LI, T. W., & Kang, J. X. (2013) · Prostaglandins Leukotrienes and Essential Fatty Acids · doi:10.1016/j.plefa.2013.02.002 · Cited by 76 · see citing works
YOSHIKAWA, M., Murakami, T., Tomohiko, U. E. D. A., Yoshizumi, S., Ninomiya, K., MURAKAMI, N., Matsuda, H., Saito, M., FUJII, W., TANAKA, T., et al. (1997) · YAKUGAKU ZASSHI · doi:10.1248/yakushi1947.117.2_108 · Cited by 69 · see citing works
Li, Y. ‐., Ji, D.-F., Zhong, S., Shi, L., Hu, G.-Y., & Chen, S. (2010) · Alcohol and Alcoholism · doi:10.1093/alcalc/agq034 · Cited by 67 · see citing works
Semen Hoveniae extract protects against acute alcohol-induced liver injury in mice
Du, J., He, D., Sun, L.-N., Han, T., Zhang, H., Qin, L., & Rahman, K. (2010) · Pharmaceutical Biology · doi:10.3109/13880200903300196 · Cited by 54 · see citing works
Yang, S.-A., Jung, Y.-S., Lee, S., Park, S.-C., Kim, M.-J., Lee, E., Byun, H.-J., Jhee, K.-H., & Lee, S.-P. (2014) · Food and Chemical Toxicology · doi:10.1016/j.fct.2014.02.010 · Cited by 47 · see citing works
Self-citationChen, Y., Singh, S. P., Matsumoto, A., Manna, S., Abdelmegeed, M. A., Golla, S., Murphy, R. C., Dong, H., Song, B., Gonzalez, F. J., et al. (2016) · Scientific Reports · doi:10.1038/srep29743 · Cited by 46 · see citing works
Xiang, J., Zhu, W., Li, Z., & Ling, S. (2012) · Food & Function · doi:10.1039/c2fo10266h · Cited by 44 · see citing works
Norikura, T., Kojima‐Yuasa, A., Kennedy, D. O., & Matsui‐Yuasa, I. (2006) · Amino Acids · doi:10.1007/s00726-006-0381-3 · Cited by 43 · see citing works
Identification of γ-aminobutyric acid receptor subunit types in human and rat liver
Erlitzki, R., Gong, Y., Zhang, M., & Minuk, G. Y. (2000) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.2000.279.4.g733 · Cited by 42 · see citing works
de Rezende, T. P., Corrêa, J. O. D. A., Aarestrup, B. J. V., Aarestrup, F. M., de Sousa, O. V., & Filho, A. A. D. S. (2014) · Molecules · doi:10.3390/molecules19079257 · Cited by 42 · see citing works
Kim, B., Woo, M. J., Park, C. S., Lee, S., Kim, J., Kim, B., An, S., & Kim, S. (2016) · Phytotherapy Research · doi:10.1002/ptr.5741 · Cited by 42 · see citing works
Self-citationThe AMPK pathway mediates an anti-adipogenic effect of fruits of Hovenia dulcis Thunb.
Kim, H., Sim, J., Choi, H.-M., Choi, I.-Y., Jeong, M., Park, J. B., Jung, Y., Youn, D., Cho, J., Kim, J., et al. (2014) · Food & Function · doi:10.1039/c4fo00470a · Cited by 37 · see citing works
Preventive effects of a novel herbal mixture on atopic dermatitis-like skin lesions in BALB/C mice
Mechesso, A. F., Lee, S. J., Park, N., Kim, J.-Y., Im, Z.-E., Suh, J., & Park, S.-C. (2019) · BMC Complementary and Alternative Medicine · doi:10.1186/s12906-018-2426-z · Cited by 32 · see citing works
Self-citationFang, H., Lin, H., Chan, M.-C., Lin, W. S., & Lin, W. (2007) · The American Journal of Chinese Medicine · doi:10.1142/s0192415x07005181 · Cited by 31 · see citing works
Suppression of PGC-1alpha by Ethanol: Implications of Its Role in Alcohol Induced Liver Injury.
Chaung, W. W., Jacob, A., Ji, Y., & Wang, P. (2008) · PubMed Central · Cited by 29 · see citing works
Morales, P., Maieves, H. A., Días, M. I., Ricardo, C. C., Sánchez‐Mata, M. D. C., Santos‐Buelga, C., Barros, L., & Ferreira, I. C. F. R. (2016) · Journal of Functional Foods · doi:10.1016/j.jff.2016.12.003 · Cited by 27 · see citing works
Wang, S., Sui, S., Liu, Z., Peng, C. Y., Liu, J., Luo, D., Fan, X., Liu, C., & Lu, W. (2017) · Journal of Applied Toxicology · doi:10.1002/jat.3544 · Cited by 24 · see citing works
Proinflammatory cytokines in alcohol or gallstone induced acute pancreatitis. A prospective study.
Novovic, S., Andersen, A. M., Ersbøll, A. K., Nielsen, O. H., Jørgensen, L. N., & Hansen, M. B. (2009) · PubMed · Cited by 23 · see citing works
Glutamate contributes to alcohol hepatotoxicity by enhancing oxidative stress in mitochondria
Teplova, V. V., Kruglov, A. G., Kovalyov, L. I., Nikiforova, A. B., Fedotcheva, N. I., & Lemasters, J. J. (2017) · Journal of Bioenergetics and Biomembranes · doi:10.1007/s10863-017-9713-0 · Cited by 23 · see citing works
Kim, Y., Park, J., Kwon, Y.-B., Lim, D. W., Song, M., Choi, H.-Y., & Kim, H. (2013) · The Korea Journal of Herbology · doi:10.6116/kjh.2013.28.4.25 · Cited by 10 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Hou, D., Tang, J., Feng, Q., Niu, Z., Shen, Q., Wang, L., & Zhou, S. (2023) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2023.2204373 · Cited by 179 · see citing works
İçer, M. A., Sarıkaya, B., Koçyiğit, E., Atabılen, B., Çelik, M. N., Capasso, R., Ağagündüz, D., & Budán, F. (2024) · Foods · doi:10.3390/foods13152437 · Cited by 102 · see citing works
Boby, N., Lee, E., Abbas, M. A., Park, N., Lee, S., Ali, M. S., Lee, S., & Park, S. (2021) · Foods · doi:10.3390/foods10102381 · Cited by 31 · see citing works
Self-citationKhan, M. Z., Shabbir, M. I., Saqib, Z., Gilani, S. A., Jogezai, N. U., Kiyani, M. M., & Arshad, M. M. U. D. (2020) · Open Chemistry · doi:10.1515/chem-2020-0062 · Cited by 21 · see citing works
Boby, N., Abbas, M. A., Lee, E., Im, Z.-E., Lee, S., & Park, S. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.113629 · Cited by 17 · see citing works
Self-citationTeng, J., Yu, T., & Yan, F. (2024) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2024.173214 · Cited by 17 · see citing works
Deng, M., Zhang, S., Wu, S., Jiang, Q., Teng, W., Luo, T., Ouyang, Y., Liu, J., & Gu, B. (2024) · Frontiers in Microbiology · doi:10.3389/fmicb.2024.1390293 · Cited by 15 · see citing works
de Godoi, R. S., Garcia, A. L. H., Borges, M. S., George, H. K., Ferraz, A. D. B. F., Corrêa, D. S., da Silva, F. R., & da Silva, J. (2022) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2022.116042 · Cited by 11 · see citing works
Chen, W., Deng, Y.-Y., Yu, J.-W., Leung, Y.-T., Bai, J., Chen, Y., Wu, Y., Wang, L., Wang, X., Wang, X.-Q., et al. (2023) · Phytomedicine · doi:10.1016/j.phymed.2023.154802 · Cited by 10 · see citing works
Lee, H., Hwangbo, H., Ji, S. Y., Kim, M. Y., Kim, S. Y., Kim, D. H., Hong, S. H., Lee, S. J., Assefa, F., Kim, G., et al. (2020) · Molecules · doi:10.3390/molecules25194375 · Cited by 9 · see citing works
Self-citationCen, X., Wang, W. J., Hong, S., Wang, Q., Wang, N., Mo, L., Li, J., & Li, J. (2024) · Food & Function · doi:10.1039/d4fo02309a · Cited by 6 · see citing works
Son, Y., Lee, D. H., Park, G. H., Jang, J.-H., Kim, J. A., Park, Y., Lee, S.-Y., & Kim, H. J. (2023) · Diversity · doi:10.3390/d15080905 · Cited by 4 · see citing works
Self-citationHoveniae Semen Seu Fructus water extract inhibits influenza A virus infection
Cho, W., Ho, M., Yim, N., Choi, H.-J., & Yeul, J. (2023) · Journal of Functional Foods · doi:10.1016/j.jff.2023.105940 · Cited by 4 · see citing works
Volvariella volvacea Polypeptide Mitigates Alcohol-Induced Liver Injury: A Multi-Omics Study
Chen, B., Chen, J., Wu, H., Zhang, F., Chen, L., Zhang, W., Yang, J., Li, Y., Jiang, Y., & Deng, Y. (2025) · Foods · doi:10.3390/foods14091557 · Cited by 3 · see citing works
Bioenrichment technology of γ-aminobutyric acid
Li, Y., Zhao, L., Wang, K., Hu, Z., & Liu, X. (2023) · Food Nutrition Chemistry · doi:10.18686/fnc.v1i3.82 · Cited by 1 · see citing works
Nakamura, A., Tanaka, S., Shimizu, H., Hokazono, H., Toi, M., & Itou, J. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.01.04.631336
- Authors
- Park, N.-H., Lee, S.-J., Mechesso, A. F., Boby, N., Yixian, Q., Yoon, W.-K., Lee, S.-P., Lee, J.-S., & Park, S.-C.
- Affiliations
- Kyungpook National University (KR)
- Keimyung University (KR)
- Gyeonggido Business and Science Accelerator (KR)
- Corresponding author
- Park, Seung-Chun
- ORCID
- Venue
- BMC Complementary Medicine and Therapies
- Published
- 2020-03-06
- Volume
- 20
- Issue
- 1
- Pages
- 75-75
- ISSN
- 2662-7671 (ISSN-L)
- PMC
- PMC7076742
- OpenAlex
- W3012539421
- Cited by
- 16
- References
- 39
- Citations by year
- 2025: 2 · 2024: 4 · 2023: 5 · 2022: 2 · 2021: 1 · 2020: 2
- FWCI
- 1.64
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- BMC Complementary Medicine and Therapies (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry and Fisheries (314082-3)
- Kyungpook National University Development Project (Research Fund, 2018)
- Ministry of SMEs and Startups (R&D, P0002954)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Life Sciences › Agricultural and Biological Sciences › Plant Science › GABA and Rice Research
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal plant effects and applications
- Keywords
- Hovenia dulcis, fermented plant extract, GABA, ethanol-induced liver injury, hepatoprotection, Bacillus subtilis fermentation, Lactobacillus plantarum, alcohol dehydrogenase, aldehyde dehydrogenase, antioxidant enzymes, PPARα, PGC-1α, fatty acid oxidation, lipogenesis, CYP2E1, liver histopathology, alcohol metabolism genes, glutamate, alcoholic liver disease
- MeSH terms
- Ethanol, Animals, Chromatography, Disease Models, Animal, Fermentation, gamma-Aminobutyric Acid, Mice, Inbred C57BL, Plant Extracts, Mass Spectrometry, Oxidative Stress, Rhamnaceae, Lipogenesis, Mice, Chemical and Drug Induced Liver Injury, Republic of Korea
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
