Gnetum montanum extract ameliorates ethanol-induced hepatic injury and metabolic dysfunction via inhibition of xanthine oxidase

Hong-Linh Tran , Thuy-Duong Nguyen , Thu-Hang Nguyen , Hai-Nam Nguyen , Duc-Vinh Pham

Asian Pacific Journal of Tropical Biomedicine ›› 2025, Vol. 15 ›› Issue (3) : 98 -108.

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Asian Pacific Journal of Tropical Biomedicine ›› 2025, Vol. 15 ›› Issue (3) : 98 -108. DOI: 10.4103/apjtb.apjtb_746_24
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Gnetum montanum extract ameliorates ethanol-induced hepatic injury and metabolic dysfunction via inhibition of xanthine oxidase

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Abstract

Objective: To investigate the effects of a crude extract from Gnetum montanum Markgr. on ethanol-induced hepatotoxicity and metabolic disorders.

Methods: Alcoholic liver disorder was induced in mice by administering increasing doses of ethanol via oral gavage. Biomarkers of liver injury and oxidative stress were assessed at the end of the study. Liver tissue damage and fat deposition were evaluated using hematoxylin and eosin and oil red O staining, respectively. In addition, key biomarkers were examined in acetaldehyde-treated HepG2 cells.

Results: Ethanol consumption induced characteristic pathological changes, including elevated serum markers of liver injury, hepatic lipid accumulation, and oxidative stress in liver tissues. Oral administration of Gnetum montanum extract (175 and 350 mg/kg) decreased serum aspartate aminotransferase, alanine aminotransferase, γ-glutamyl transferase, and bilirubin levels in ethanol-treated mice. The extract also lowered triglyceride levels in serum and liver tissue in a dose-dependent manner. Furthermore, it mitigated malondialdehyde levels, preserved reduced glutathione levels, and enhanced catalase activity and total antioxidant capacity in liver tissue homogenates. Additionally, ethanol-induced hyperuricemia was suppressed by Gnetum montanum extract by inhibiting xanthine oxidase activity. Similar effects were observed in Gnetum montanum extract-treated HepG2 cells.

Conclusions: This study demonstrates that Gnetum montanum extract alleviates ethanol-induced hepatic injury by alleviating oxidative stress and inhibiting xanthine oxidase activity.

Keywords

Alcoholic liver disease / Gnetum montanum / Hepatic steatosis / Hepatoprotective effect / Xanthine oxidase

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Hong-Linh Tran, Thuy-Duong Nguyen, Thu-Hang Nguyen, Hai-Nam Nguyen, Duc-Vinh Pham. Gnetum montanum extract ameliorates ethanol-induced hepatic injury and metabolic dysfunction via inhibition of xanthine oxidase. Asian Pacific Journal of Tropical Biomedicine, 2025, 15(3): 98-108 DOI:10.4103/apjtb.apjtb_746_24

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Conflict of interest statement

The authors have no conflict of interest.

Funding

This research was funded by Vietnam National Foundation for Science and Technology Development under grant number 108.05-2023.23.

Data availability statement

The data supporting the findings of this study are available from the corresponding authors upon request.

Authors’ contributions

HLT performed the experiments, collected data, and drafted the manuscript. Both TDN and THN contributed to the experimental design and data analysis. TDN secured funding for the project. HNN and DVP critically revised the manuscript and were responsible for the final version. DVP conceived the idea and supervised the project.

Publisher’s note

The Publisher of the Journal remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

References

[1]

Singal AK, Mathurin P. Diagnosis and treatment of alcohol-associated liver disease: A review. JAMA 2021; 326(2): 165-176.

[2]

Devarbhavi H, Asrani SK, Arab JP, Nartey YA, Pose E, Kamath PS. Global burden of liver disease: 2023 update. J Hepatol 2023; 79(2): 516537.

[3]

Ha Y, Jeong I, Kim TH. Alcohol-related liver disease: An overview on pathophysiology, diagnosis and therapeutic perspectives. Biomedicines 2022; 10(10). doi: 10.3390/biomedicines10102530.

[4]

Ryu T, Kim K, Choi SE, Chung KPS, Jeong WI. New insights in the pathogenesis of alcohol-related liver disease: The metabolic, immunologic, and neurologic pathways. Liver Res 2023; 7(1): 1-8.

[5]

Yan C, Hu W, Tu J, Li J, Liang Q, Han S. Pathogenic mechanisms and regulatory factors involved in alcoholic liver disease. J Transi Med 2023; 21(1): 300.

[6]

Yin H, Hu M, Liang X, Ajmo JM, Li X, Bataller R, et al. Deletion of SIRT1 from hepatocytes in mice disrupts lipin-1 signaling and aggravates alcoholic fatty liver. Gastroenterology 2014; 146(3): 801-811.

[7]

Ding RB, Tian K, Huang LL, He CW, Jiang Y, Wang YT, et al. Herbal medicines for the prevention of alcoholic liver disease: A review. J Ethnopharmacol 2012; 144(3): 457-465.

[8]

Allameh A, Niayesh-Mehr R, Aliarab A, Sebastiani G, Pantopoulos K. Oxidative stress in liver pathophysiology and disease. Antioxidants (Basel) 2023; 12(9). doi: 10.3390/antiox12091653.

[9]

Conde de la Rosa L, Goicoechea L, Torres S, Garcia-Ruiz C, Fernandez-Checa JC. Role of oxidative stress in liver disorders. Livers 2022; 2(4): 283-314.

[10]

Yang YM, Cho YE, Hwang S. Crosstalk between oxidative stress and inflammatory liver injury in the pathogenesis of alcoholic liver disease. Int J Mol Sci 2022; 23(2). doi: 10.3390/ijms23020774.

[11]

Bortolotti M, Polito L, Battelli MG, Bolognesi A. Xanthine oxidoreductase: One enzyme for multiple physiological tasks. Redox Biol 2021; 41: 101882.

[12]

Yagi C, Kusunoki Y, Tsunoda T, Murase T, Nakamura T, Osugi K, et al. Xanthine oxidoreductase activity is correlated with hepatic steatosis. Sci Rep 2022; 12(1): 12282.

[13]

Liu L, Zhang Y, Wang X, Meng H, He Y, Xu X, et al. Xanthine oxidase promotes hepatic lipid accumulation through high fat absorption by the small intestine. JHEP Rep 2024; 6(8): 101060.

[14]

Hu S, Li SW, Yan Q, Hu XP, Li LY, Zhou H, et al. Natural products, extracts and formulations comprehensive therapy for the improvement of motor function in alcoholic liver disease. Pharmacol Res 2019; 150: 104501.

[15]

Mancak M, Altintas D, Balaban Y, Caliskan UK. Evidence-based herbal treatments in liver diseases. Hepatol Forum 2024; 5(1): 50-60.

[16]

Nguyen TVT, Ho DC, Bui HT, Phan VK. Stilbene derivatives from Gnetum montanum Markgr. with their xanthine oxidase inhibition activity. Vietnam J Chem 2024; 62(6): 766-771.

[17]

Ma YQ, Zhai YM, Deng Y, Guo L, Wan YQ, Tan CH. Stilbeno-phenylpropanoids from Gnetum montanum Markgr. Phytochem Lett 2017; 21: 42-45.

[18]

Pan X, Hou X, Zhang F, Tang P, Wan W, Su Z, et al. Gnetum montanum extract induces apoptosis by inhibiting the activation of AKT in SW480 human colon cancer cells. Pharm Biol 2022; 60(1): 915-930.

[19]

Nguyen CN, Antoniadi L, Tran H, Huynh TN, Stuppner H, Angelis A, et al. Phytochemical analysis of Gnetum montanum stems’ ethanol extract and in vitro evaluation of tyrosinase and elastase inhibitory activity. Planta Med 2021; 87(15): PC9-59.

[20]

Pérez M, Dominguez-López I, Lamuela-Raventós RM. The chemistry behind the Folin-Ciocalteu method for the estimation of (poly)phenol content in food: Total phenolic intake in a mediterranean dietary pattern. J Agric Food Chem 2023; 71(46): 17543-17553.

[21]

Nguyen TT, Tran CS, Nguyen HA, Nguyen TD, Chi SC, Pham DV, et al. Formulation and biopharmaceutical evaluation of supersaturatable self-nanoemulsifying drug delivery systems containing silymarin. Int J Pharm 2019; 555: 63-76.

[22]

Hadwan MH, Abed HN. Data supporting the spectrophotometric method for the estimation of catalase activity. Data Brief 2016; 6: 194-199.

[23]

Nguyen TD, Pham DV, Phuong TT, Nguyen TH, Le NT, Tran TB, et al. Xanthine oxidase inhibitors from Archidendron clypearia (Jack.) I.C. Nielsen: Results from systematic screening of Vietnamese medicinal plants. Asian Pac J Trop Med 2017; 10(6): 549-556.

[24]

Nguyen QC, Nguyen HA, Pham TA, Tran VTH, Nguyen TD, Pham DV. Mimosa pudica L. extract ameliorates pulmonary fibrosis via modulation of MAPK signaling pathways and FOXO 3 stabilization. J Ethnopharmacol 2024; 330: 118226.

[25]

Nguyen TH, Nguyen HHN, Nguyen TD, Tran VTH, Nguyen HA, Pham DV. NLRP3 inflammasome activation contributes to the development of the pro-fibrotic phenotype of lung fibroblasts. Biochem Pharmacol 2024; 229: 116496.

[26]

Chen M, Zhong W, Xu W. Alcohol and the mechanisms of liver disease. J Gastroenterol Hepatol 2023; 38(8): 1233-1240.

[27]

Ferdouse A, Clugston RD. Pathogenesis of alcohol-associated fatty liver: Lessons from transgenic mice. Front Physiol 2022; 13: 940974.

[28]

Nevzorova YA, Boyer-Diaz Z, Cubero FJ, Gracia-Sancho J. Animal models for liver disease-A practical approach for translational research. J Hepatol 2020; 73(2): 423-440.

[29]

Jiménez-López JM, Carrasco MaP, Segovia JL, Marco C. Resistance of HepG2 cells against the adverse effects of ethanol related to neutral lipid and phospholipid metabolism. Biochem Pharmacol 2002; 63(8): 1485-1490.

[30]

Ali H, Assiri MA, Shearn CT, Fritz KS. Lipid peroxidation derived reactive aldehydes in alcoholic liver disease. Curr Opin Toxicol 2019; 13: 110-117.

[31]

Yamamoto T, Moriwaki Y, Takahashi S. Effect of ethanol on metabolism of purine bases (hypoxanthine, xanthine, and uric acid). Clinica Chimica Acta 2005; 356(1): 35-57.

[32]

Abbondanza A, Battelli MG, Soffritti M, Cessi C. Xanthine oxidase status in ethanol-intoxicated rat liver. Alcohol Clin Exp Res 1989; 13(6): 841-844.

[33]

Al-Shargi A, El Kholy AA, Adel A, Hassany M, Shaheen SM. Allopurinol versus Febuxostat: A new approach for the management of hepatic steatosis in metabolic dysfunction-associated steatotic liver disease. Biomedicines 2023; 11(11). doi: 10.3390/biomedicines11113074.

[34]

Pauff JM, Hille R. Inhibition studies of bovine xanthine oxidase by luteolin, silibinin, quercetin, and curcumin. J Nat Prod 2009; 72(4): 725731.

[35]

Hameed B. Antihyperuricemic and xanthine oxidase inhibitory activities of silymarin in a rat gout model. Int J Green Pharm 2018; 12(3): S695.

[36]

Acquaviva R, Russo A, Campisi A, Sorrenti V, Giacomo C, Barcellona M, et al. Antioxidant activity and protective on DNA cleavage of resveratrol. J Food Sci 2006; 67: 137-141.

[37]

Petrella C, Carito V, Carere C, Ferraguti G, Ciafrè S, Natella F, et al. Oxidative stress inhibition by resveratrol in alcohol-dependent mice. Nutrition 2020; 79-80: 110783.

[38]

Bujanda L, García-Barcina M, Gutiérrez-de Juan V, Bidaurrazaga J, de Luco MF, Gutiérrez-Stampa M, et al. Effect of resveratrol on alcohol-induced mortality and liver lesions in mice. BMC Gastroenterol 2006; 6: 35.

[39]

You M, Jogasuria A, Taylor C, Wu J. Sirtuin 1 signaling and alcoholic fatty liver disease. Hepatobiliary Surg Nutr 2015; 4(2): 88-100.

[40]

Pham DV, Park PH. Adiponectin triggers breast cancer cell death via fatty acid metabolic reprogramming. J Exp Clin Cancer Res 2022; 41(1): 9.

[41]

Kim H, Baek CH, Chang JW, Yang WS, Lee SK. Febuxostat, a novel inhibitor of xanthine oxidase, reduces ER stress through upregulation of SIRT1-AMPK-HO-1/thioredoxin expression. Clin Exp Nephrol 2020; 24(3): 205-215.

[42]

Cheung KJ, Tzameli I, Pissios P, Rovira I, Gavrilova O, Ohtsubo T, et al. Xanthine oxidoreductase is a regulator of adipogenesis and PPARγ activity. Cell Metab 2007; 5(2): 115-128.

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