Evaluation of the Protective Efficiency of Ethyl Gallate Against Non-Alcoholic Fatty Liver Disease Induced by a High-Fat Diet in Mice
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Abstract
A significant portion of the population is affected by nonalcoholic fatty liver disease (NAFLD). Unfortunately, there are no particular pharmacological treatments that have been approved for it. This study aimed to investigate the protective effect of ethyl gallate against NAFLD induced by a high-fat diet in mice. By using a high-fat diet for 16 weeks, the NAFLD model was created in mice. Two oral doses of ethyl gallate (20 mg/kg and 40 mg/kg) were given. The liver injury was assessed by the liver index, along with serum evaluations of liver functions and lipid profiles. A histopathology study was also performed. Triglyceride (TG) and sterol regulatory element-binding protein 1C (SREBP-1C) levels in the liver were also measured, and the liver's oxidative stress and inflammation were assessed. The results demonstrated that ethyl gallate could mitigate the liver injury, particularly when it was administered at the high dose. It resulted in a reduction in both the liver index and NAFLD activity score. In addition, it improved significantly the liver function and reduced serum TG levels. Furthermore, by decreasing the liver levels of tumor necrosis factor alpha (TNF-α) and nuclear factor kappa B (NF-κB), ethyl gallate showed an anti-inflammatory effect, and it also could reduce oxidative stress. Moreover, the high dose of ethyl gallate reduced the hepatic TG and SREBP-1C levels. In conclusion, by controlling lipid metabolism, lowering oxidative stress, and suppressing the NF-κB signaling pathway, ethyl gallate provides protection against NAFLD.
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1.Lazarus JV, Ekstedt M, Marchesini G, Mullen J, Novak K, Pericàs JM, Roel E, Romero-Gómez M, Ratziu V, Tacke F, Cortez-Pinto H. A cross-sectional study of the public health response to non-alcoholic fatty liver disease in Europe. J Hepatol. 2020; 72(1):14-24.
2.Sukkasem N, Chatuphonprasert W, Jarukamjorn K. Hesperidin and myricetin attenuated non-alcoholic fatty liver disease (NAFLD) in HepG2 cells. Trop J Nat Prod Res. 2020; 4(10), 739-747
3.Loomba R, Friedman SL, Shulman GI. Mechanisms and disease consequences of nonalcoholic fatty liver disease. Cell. 2021; 184(10): 2537-2564.
4.Mitra S, De A, Chowdhury A. Epidemiology of non-alcoholic and alcoholic fatty liver diseases. Transl. Gastroenterol Hepatol. 2020; 5: 1-17.
5.Caturano A, Acierno C, Nevola R, Pafundi PC, Galiero R, Rinaldi L, Salvatore T, Adinolfi LE, Sasso FC. Non-alcoholic fatty liver disease: From pathogenesis to clinical impact. Processes. 2021; 9(1): 1-18.
6.Han SK, Baik SK, Kim MY. Non-alcoholic fatty liver disease: Definition and subtypes. Clin Mol Hepatol. 2022; 29(Suppl): 5-16.
7.Li J, Xie S, Teng W. Sulforaphane attenuates nonalcoholic fatty liver disease by inhibiting hepatic steatosis and apoptosis. Nutrients. 2021;14(1): 1-13.
8.Rathnayake Wathsala D, Sooriyaarachchi P, Niriella Anuk M, Ediriweera D, Perera J. Herbal treatments for non-alcoholic fatty liver disease: A systematic review and meta-analysis of randomized controlled trials. Adv. Integr. Med. 2024: 1-21.
9.Mohan S, Thiagarajan K, Chandrasekaran R, Arul J. In vitro protection of biological macromolecules against oxidative stress and in vivo toxicity evaluation of Acacia nilotica (L.) and ethyl gallate in rats. BMC Complement Altern Med. 2014; 14:1-13.
10.Chougule PR, Sangaraju R, Patil PB, Qadri SS, Panpatil VV, Ghosh S, Mungamuri SK, Bhanoori M, Sinha SN. Effect of ethyl gallate and propyl gallate on dextran sulfate sodium (DSS)-induced ulcerative colitis in C57BL/6 J mice: preventive and protective. Inflammopharmacology. 2023; 31(4): 2103-2120.
11.Muddu KC, Jayaprakash NK, Asha S, Sravan KRT. Biological Potential of Ethyl Gallate. Res. J. Biotechnol. 2023;19(1):122–125.
12.Kim WH, Song HO, Choi HJ, Bang HI, Choi DY, Park H. Ethyl gallate induces apoptosis of HL-60 cells by promoting the expression of caspases-8,-9,-3, apoptosis-inducing factor and endonuclease G. Int J Mol Sci. 2012; 13(9): 11912-11922.
13.Albuquerque BR, Heleno SA, Oliveira MB, Barros L, Ferreira IC. Phenolic compounds: Current industrial applications, limitations and future challenges. Food Funct. 2021;12(1):14-29.
14.Sahin E, Bagci R, Bektur Aykanat NE, Kacar S, Sahinturk V. Silymarin attenuated nonalcoholic fatty liver disease through the regulation of endoplasmic reticulum stress proteins GRP78 and XBP‐1 in mice. J. Food Biochem. 2020;44(6):e13194.
15.Ezhilarasan D, Shree Harini K, Karthick M, Selvaraj C. Ethyl gallate concurrent administration protects against acetaminophen‐induced acute liver injury in mice: An in vivo and in silico approach. Chem. Biol. Drug Des. 2024; 103(1):e14369.
16.Zhao W, Yan Y, Xiao Z, Wang M, Xu M, Wang Z, Wang Y, Zhuang Z, Yang D, Chen G, Liang G. Bicyclol ameliorates nonalcoholic fatty liver disease in mice via inhibiting MAPKs and NF-κB signaling pathways. Biomed Pharmacother.. 2021; 141:1-10.
17.Kim B, Kwon J, Kim MS, Park H, Ji Y, Holzapfel W, Hyun CK. Protective effects of Bacillus probiotics against high-fat diet-induced metabolic disorders in mice. PloS one. 2018;13(12): 1-17.
18.Nagababu E, Rifkind JM, Boindala S, Nakka L. Assessment of antioxidant activity of eugenol in vitro and in vivo. Free Radic. Antioxid. 2009; 610, 165–180.
19.Barroso MV, Graça-Reis A, Cattani-Cavalieri I, Gitirana LB, Valenca SS, Lanzetti M. Mate tea reduces high fat diet-induced liver and metabolic disorders in mice. Biomed Pharmacother 2019; 109:1547-1555.
20.Rahman I, Kode A, Biswas SK. Assay for quantitative determination of glutathione and glutathione disulfide levels using enzymatic recycling method. Nat. Protoc. 2006; 1(6):3159-3165.
21.Gravandi MM, Alidoust H, Tahvilian M, Moradi E, Hashemnia M, Behbood L, Naseri M, Farzaei MH. Evaluating the Protective Effect of Rutin Nanoformulation in a Rat Model of Acetic Acid-Induced Ulcerative Colitis. Apoptosis. 2025; 20(1): 1-14.
22.Li X. Improved pyrogallol autoxidation method: a reliable and cheap superoxide-scavenging assay suitable for all antioxidants. J Agric Food Chem. 2012; 60(25):6418-6424.
23.Cohen G, Dembiec D, Marcus J. Measurement of catalase activity in tissue extracts. Anal Biochem. 1970; 34(1):30-38.
24.Mu H, Zhou Q, Yang R, Zeng J, Li X, Zhang R, Tang W, Li H, Wang S, Shen T, Huang X. Naringin attenuates high fat diet induced non-alcoholic fatty liver disease and gut bacterial dysbiosis in mice. Front Microbiol. 2020;11:1-15.
25.Ahn D, Kim J, Nam G, Zhao X, Kwon J, Hwang JY, Kim JK, Yoon SY, Chung SJ. Ethyl gallate dual-targeting PTPN6 and PPARγ shows anti-diabetic and anti-obese effects. Int J Mol Sci. 2022;23(9):1-16.
26.Gowda D, Shekhar C, B. Gowda SG, Chen Y, Hui SP. Crosstalk between Lipids and Non-Alcoholic Fatty Liver Disease. Livers. 2023; 3(4): 687–708.
27.Li N, Li X, Ding Y, Liu X, Diggle K, Kisseleva T, Brenner DA. SREBP regulation of lipid metabolism in liver disease, and therapeutic strategies. Biomed. 2023; 11(12):1-17.
28.Wu L, Guo T, Deng R, Liu L, Yu Y. Apigenin ameliorates insulin resistance and lipid accumulation by endoplasmic reticulum stress and SREBP-1c/SREBP-2 pathway in palmitate-induced HepG2 cells and high-fat diet–fed mice. J. Pharmacol. Exp. Ther. 2021; 377(1):146-156.
29.Zhang Y, Meng T, Zuo L, Bei Y, Zhang Q, Su Z, Huang Y, Pang J, Xiang Q, Yang H. Xyloketal B attenuates fatty acid-induced lipid accumulation via the SREBP-1c pathway in NAFLD models. Mar. Drugs. 2017; 15(6):1-14.
30.Akbari R, Yaghooti H, Jalali MT, Khorsandi LS, Mohammadtaghvaei N. Capparis spinosa improves non-alcoholic steatohepatitis through down-regulating SREBP-1c and a PPAR α-independent pathway in high-fat diet-fed rats. BMC Res Notes. 2022; 15(1):1-8.
31.Martín-Fernández M, Arroyo V, Carnicero C, Sigüenza R, Busta R, Mora N, Antolín B, Tamayo E, Aspichueta P, Carnicero-Frutos I, Gonzalo-Benito H. Role of oxidative stress and lipid peroxidation in the pathophysiology of NAFLD. Antioxidants. 2022;11(11):1-10.
32.Kalaivani T, Rajasekaran C, Shalini M, Vijayakumar V, Pandey DP, Mathew L. Structural Elucidation and Antioxidant Activity of Ethyl Gallate Isolated from Acacia nilotica (L.) Wild. ex. Delile subsp. indica (Benth.) Brenan. Natl. Acad. Sci. Lett. 2018; 41:355-359.
33.Chen L, Wu X, Shen T, Wang X, Wang S, Wang J, Ren D. Protective effects of ethyl gallate on H 2 O 2-induced mitochondrial dysfunction in PC12 cells. Metab Brain Dis. 2019; 34:545-555.
34.Bhat P, Patil VS, Anand A, Bijjaragi S, Hegde GR, Hegde HV, Roy S. Ethyl gallate isolated from phenol-enriched fraction of Caesalpinia mimosoides Lam. Promotes cutaneous wound healing: a scientific validation through bioassay-guided fractionation. Front Pharmacol. 2023; 14:1-22.
35.Zhou Y, Ding YL, Zhang JL, Zhang P, Wang JQ, Li ZH. Alpinetin improved high fat diet-induced non-alcoholic fatty liver disease (NAFLD) through improving oxidative stress,
inflammatory response and lipid metabolism. Biomed Pharmacother. 2018; 97:1397-1408.
36.Yuan S, Liu H, Yuan D, Xu J, Chen Y, Xu X, Xu F, Liang H. PNPLA3 I148M mediates the regulatory effect of NF‐kB on inflammation in PA‐treated HepG2 cells. J. Cell. Mol. Med. 2020; 24(2):1541-1552.
37.Yu H, Lin L, Zhang Z, Zhang H, Hu H. Targeting NF-κB pathway for the therapy of diseases: mechanism and clinical study. Signal Transduct Target Ther. 2020; 5(1):1-23.
38.Rafaqat S, Gluscevic S, Mercantepe F, Rafaqat S, Klisic A. Interleukins: pathogenesis in non-alcoholic fatty liver disease. Metabolites. 2024; 14(3):1-22.
39.Fan S, Feng X, Li K, Li B, Diao Y. Protective Mechanism of Ethyl Gallate against Intestinal Ischemia‐Reperfusion Injury in Mice by in Vivo and in Vitro Studies Based on Transcriptomics. Chemistry & Biodiversity. 2023; 20(1):e202200643.