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Protective role of hydroalcoholic extract of Medusomyces gisevii L. in non-alcoholic fatty liver disease: insights from a murine model
Abstract
Background and purpose: This study explored the impact of the hydroalcoholic extract of Medusomyces gisevii L. (HEMG), a promising source for dietary use, on NAFLD in male mice.
Experimental approach: The essential oil of MG was characterized using GC-MS and the HEMG, obtained through continuous maceration. Male albino mice were subjected to 7 groups (n = 9), including normal diet, high-fat diet (HFD, 12 weeks), HEMG (62.5, 125, 250, and 500 mg/kg, orally, 8 weeks), or vitamin E (20 mg/kg, orally, 8 weeks) supplementation with HFD. Blood samples were analyzed for serum biomarkers, and liver mitochondria were isolated to assess oxidative stress markers. Histopathological examinations of liver tissue were conducted.
Findings/Results: MG was rich in cyclohexanol, carvacrol, and phenol, with HEMG exhibiting an antioxidant activity of 50.14 ± 3.56 μg/mL. It contained 73.47 ± 0.85 mg of gallic acid equivalents per g of TPC and 62.56 ± 1.30 mg/g of TTC, indicating the significant antioxidant properties of HEMG. Mice on an HFD exhibited elevated serum biomarkers, including ALT, AST, ALP, TG, TC, and LDL, along with a reduction in HDL levels. Oxidative stress factors, including ROS, protein carbonyl, and MDA, increased, while mitochondrial function, GSH, catalase, and SOD were decreased in the NAFLD groups. Furthermore, treatment with HEMG supplementation led to improvements in serum biomarkers and enhanced oxidative stress markers, thus alleviating liver damage and hepatic steatosis caused by the HFD.
Conclusion and implications: These results suggest that HEMG holds promise as a candidate in addressing NAFLD.
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Mun J, Kim S, Yoon HG, You Y, Kim OK, Choi KC, et al. Water extract of Curcuma longa L. ameliorates non-alcoholic fatty liver disease. Nutrients. 2019;11(10):2536,1-13.DOI: 10.3390/nu11102536.
Guo X, Yin X, Liu Z, Wang J. Non-alcoholic fatty liver disease (NAFLD) pathogenesis and natural products for prevention and treatment. Int J Mol Sci. 2022;23(24):15489,1-18.DOI: 10.3390/ijms232415489.
Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, et al. The diagnosis and management of non‐alcoholic fatty liver disease: practice guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology. 2012;55(6):2005-2023.DOI: 10.1002/hep.25762.
Ye Q, Zou B, Yeo YH, Li J, Huang DQ, Wu Y, et al. Global prevalence, incidence, and outcomes of non-obese or lean non-alcoholic fatty liver disease: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2020;5(8):739-752.DOI: 10.1016/S2468-1253(20)30077-7.
Milić S, Lulić D, Štimac D. Non-alcoholic fatty liver disease and obesity: biochemical, metabolic and clinical presentations. World J Gastroenterol. 2014;20(28):9330-9337.DOI: 10.3748/wjg.v20.i28.9330.
Feng G, Li XP, Niu CY, Liu ML, Yan QQ, Fan LP, et al. Bioinformatics analysis reveals novel core genes associated with nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Gene. 2020;742:144549,1-5.DOI: 10.1016/j.gene.2020.144549.
Malekinejad H, Zeynali-Moghaddam S, Rezaei-Golmisheh A, Alenabi A, Malekinejad F, Alizadeh A, et al. Lupeol attenuated the NAFLD and PCOS-induced metabolic, oxidative, hormonal, histopathological, and molecular injuries in mice. Res Pharm Sci. 2023;18(5):551-565.DOI: 10.4103/1735-5362.383710.
Heeren J, Scheja L. Metabolic-associated fatty liver disease and lipoprotein metabolism. Mol Metab. 2021;50:101238,1-17.DOI: 10.1016/j.molmet.2021.101238.
Morales D, Miguel M, Garcés-Rimón M. Pseudocereals:a novel source of biologically active peptides. Crit Rev Food Sci Nutr. 2021;61(9):1537-1544.DOI: 10.1080/10408398.2020.1761774.
Gonzalez A, Huerta-Salgado C, Orozco-Aguilar J, Aguirre F, Tacchi F, Simon F, et al. Role of oxidative stress in hepatic and extrahepatic dysfunctions during nonalcoholic fatty liver disease (NAFLD). Oxid Med Cell Longev. 2020;2020:1617805,1-16.DOI: 10.1155/2020/1617805.
Presa N, Clugston RD, Lingrell S, Kelly SE, Merrill Jr AH, Jana S, et al. Vitamin E alleviates non-alcoholic fatty liver disease in phosphatidylethanolamine N-methyltransferase deficient mice. Biochim Biophys Acta, Mol Basis Dis. 2019;1865(1):14-25.DOI: 10.1016/j.bbadis.2018.10.010.
Songtrai S, Pratchayasakul W, Arunsak B, Chunchai T, Kongkaew A, Chattipakorn N, et al. Cyclosorus terminans extract ameliorates insulin resistance and non-alcoholic fatty liver disease (NAFLD) in high-fat diet (HFD)-induced obese rats. Nutrients. 2022;14(22):4895,1-19.DOI: 10.3390/nu14224895.
Sumida Y, Yoneda M, Seko Y, Takahashi H, Hara N, Fujii H, et al. Role of vitamin E in the treatment of non-alcoholic steatohepatitis. Free Radic Biol Med. 2021;177:391-403.DOI: 10.1016/j.freeradbiomed.2021.10.017.
Li S, Duan F, Li S, Lu B. Administration of silymarin in NAFLD/NASH: a systematic review and meta-analysis. Ann Hepatol. 2024;29(2):101174,1-12.DOI: 10.1016/j.aohep.2023.101174.
Noureddin M, Mato JM, Lu SC. Nonalcoholic fatty liver disease: update on pathogenesis, diagnosis, treatment and the role of S-adenosylmethionine. Exp Biol Med. 2015;240(6):809-820.DOI: 10.1177/1535370215579161.
Xiao L, Xiong H, Deng Z, Peng X, Cheng K, Zhang H, et al. Tetrastigma hemsleyanum leaf extracts ameliorate NAFLD in mice with low-grade colitis via the gut-liver axis. Food Funct. 2023;14(1):500-515.DOI: 10.1039/D2FO03028D.
Xu J, Jia W, Zhang G, Liu L, Wang L, Wu D, et al. Extract of Silphium perfoliatum L. improve lipid accumulation in NAFLD mice by regulating AMPK/FXR signaling pathway. J Ethnopharmacol. 2024;327:118054.DOI: 10.1016/j.jep.2024.118054.
Jiang G, Ramachandraiah K, Murtaza MA, Wang L, Li S, Ameer K. Synergistic effects of black ginseng and aged garlic extracts for the amelioration of nonalcoholic fatty liver disease (NAFLD) in mice. Food Sci Nutr. 2021;9(6):3091-3099.DOI: 10.1002/fsn3.2267.
Le TNH, Choi HJ, Jun HS. Ethanol extract of liriope platyphylla root attenuates non-alcoholic fatty liver disease in high-fat diet-induced obese mice via regulation of lipogenesis and lipid uptake. Nutrients. 2021;13(10):3338,1-13.DOI: 10.3390/nu13103338.
Bondareva NI, Timchenko LD, Dobrynya YM, Alieva EVe, Rzhepakovsky IV, Sizonenko M, et al. Influence of biologically active substances from Kombucha (Medusomyces gisevii) on rat gut microbiota with experimental antibiotic-associated dysbiosis. Indian J Anim Sci. 2017;87(5):624-629.DOI: 10.56093/ijans.v87i5.70256.
Flyurik EA, Ermakova OS. Medusomyces gisevii: cultivation, composition, and application. 2022;11(1):152-161.DOI: 10.21603/2308-4057-2023-1-563.
Martínez Leal J, Valenzuela Suárez L, Jayabalan R, Huerta Oros J, Escalante-Aburto A. A review on health benefits of kombucha nutritional compounds and metabolites. CyTA-J Food. 2018;16(1):390-399.DOI: 10.1080/19476337.2017.1410499.
Watawana MI, Jayawardena N, Gunawardhana CB, Waisundara VY. Health, wellness, and safety aspects of the consumption of kombucha. J Chem. 2015;2015(1):591869,1-11.DOI: 10.1155/2015/591869.
Abshenas J, Derakhshanfar A, Ferdosi MH, Hasanzadeh S. Protective effect of kombucha tea against acetaminophen-induced hepatotoxicity in mice: a biochemical and histopathological study. Comp Clin Path. 2012;21(6):1243-1248.DOI: 10.1007/s00580-011-1273-9.
Dashti A, Shokrzadeh M, Karami M, Habibi E. Phytochemical identification, acute and subchronic oral toxicity assessments of hydroalcoholic extract of Acroptilon repens in BALB/c mice: a toxicological and mechanistic study. Heliyon. 2022;8(2):1-12.DOI: 10.1016/j.heliyon.2022.e08940.
Enayatifard R, Akbari J, Babaei A, Rostamkalaei SS, Hashemi SMH, Habibi E. Anti-microbial potential of nano-emulsion form of essential oil obtained from aerial parts of Origanum vulgare L. as food additive. Adv Pharm Bull. 2020;11(2):327,1-8.DOI: 10.34172/apb.2021.028.
Habibi E, Hemmati P, Arabnozari H, Khalili HA, Sharifianjazi F, Enderami SE, et al. Phytochemical analysis and immune-modulatory potential of Trichaptum biforme polysaccharides: implications for cancer. Int J Biol Macromol. 2024;280:135691.DOI: 10.1016/j.ijbiomac.2024.135691.
Balogun FO, Ashafa AOT. Cytotoxic, kinetics of inhibition of carbohydrate-hydrolysing enzymes and oxidative stress mitigation by flavonoids roots extract of Dicoma anomala (Sond.). Asian Pac J Trop Med. 2018;11(1):24-31.DOI: 10.4103/1995-7645.223530.
Wanyo P, So-In C. The protective effect of Thai rice bran on N-acetyl-ρ-aminophen-induced hepatotoxicity in mice. Res Pharm Sci. 2024;19(2):188-202.DOI: 10.4103/RPS.RPS_210_23.
Arabnozari H, Shaki F, Saberi Najjar A, Sharifianjazi F, Sarker SD, Habibi E, et al. The effect of Polygonum hyrcanicum Rech. f. hydroalcoholic extract on oxidative stress and nephropathy in alloxan-induced diabetic mice. Sci Rep. 2024;14(1):18117,1-11.DOI: 10.1038/s41598-024-69220-x.
Wilson CG, Tran JL, Erion DM, Vera NB, Febbraio M, Weiss EJ. Hepatocyte-specific disruption of CD36 attenuates fatty liver and improves insulin sensitivity in HFD-fed mice. Endocrinology. 2016;157(2):570-585.DOI: 10.1210/en.2015-1866.
Velázquez AM, Bentanachs R, Sala‐Vila A, Lázaro I, Rodríguez‐Morató J, Sánchez RM, et al. ChREBP‐driven DNL and PNPLA3 expression induced by liquid fructose are essential in the production of fatty liver and hypertriglyceridemia in a high‐fat diet‐fed rat model. Mol Nutr Food Res. 2022;66(7):2101115,1-11.DOI: 10.1002/mnfr.202101115.
Shariatzadeh SMA, Miri SA, Cheraghi E. The protective effect of Kombucha against silver nanoparticle-induced toxicity on testicular tissue in NMRI mice. Andrologia. 2021;53(3):e13982,1-10.DOI: 10.1111/and.13982.
Alaei Z, Doudi M, Setorki M. The protective role of Kombucha extract on the normal intestinal microflora, high-cholesterol diet caused hypercholesterolemia, and histological structure changes in New Zealand white rabbits. Avicenna J Phytomed. 2020;10(6):604-614.PMCID: PMC7711297.
Hyun J, Lee Y, Wang S, Kim J, Kim J, Cha J, et al. Kombucha tea prevents obese mice from developing hepatic steatosis and liver damage. Food Sci Biotechnol. 2016;25(3):861-866.DOI: 10.1007/s10068-016-0142-3.
Karimian G, Kirschbaum M, Veldhuis ZJ, Bomfati F, Porte RJ, Lisman T. Vitamin E attenuates the progression of non-alcoholic fatty liver disease caused by partial hepatectomy in mice. PLoS One. 2015;10(11):e0143121,1-12.DOI: 10.1371/journal.pone.0143121.
Ni Y, Nagashimada M, Zhuge F, Zhan L, Nagata N, Tsutsui A, et al. Astaxanthin prevents and reverses diet-induced insulin resistance and steatohepatitis in mice: a comparison with vitamin E. Sci Rep. 2015;5(1):17192,1-15.DOI: 10.1038/srep17192.
He W, Xu Y, Ren X, Xiang D, Lei K, Zhang C, et al. Vitamin E ameliorates lipid metabolism in mice with nonalcoholic fatty liver disease via Nrf2/CES1 signaling pathway. Dig Dis Sci. 2019;64(11):3182-3191.DOI: 10.1007/s10620-019-05657-9.
Liang M, Huo M, Guo Y, Zhang Y, Xiao X, Xv J, et al. Aqueous extract of Artemisia capillaris improves non-alcoholic fatty liver and obesity in mice induced by high-fat diet. Front Pharmacol. 2022;13:1084435,1-16.DOI: 10.3389/fphar.2022.1084435.
Zare Gashti R, Mohammadi H. Sodium dithionate (Na2S2O4) induces oxidative damage in mice mitochondria heart tissue. Toxicol Rep. 2022;9: 1391-1397.DOI: 10.1016/j.toxrep.2022.06.016.
Fathi H, Ebrahimzadeh MA, Ziar A, Mohammadi H. Oxidative damage induced by retching; antiemetic and neuroprotective role of Sambucus ebulus L. Cell Biol Toxicol. 2015;31(4-5):231-239.DOI: 10.1007/s10565-015-9307-8.
Akbari G, Abasi MR, Gharaghani M, Nouripoor S, Shakerinasab N, Azizi M, et al. Antioxidant and hepatoprotective activities of Juniperus excelsa M. Bieb against bile duct ligation-induced cholestasis. Res Pharm Sci. 2024;19(2):217-227.DOI: 10.4103/RPS.RPS_52_23.
Ou X, Chen J, Li B, Yang Y, Liu X, Xu Z, et al. Multiomics reveals the ameliorating effect and underlying mechanism of aqueous extracts of Polygonatum sibiricum rhizome on obesity and liver fat accumulation in high-fat diet-fed mice. Phytomedicine. 2024;132:155843,1-18.DOI: 10.1016/j.phymed.2024.155843.
Luo X, Zhang B, Pan Y, Gu J, Tan R, Gong P. Phyllanthus emblica aqueous extract retards hepatic steatosis and fibrosis in NAFLD mice in association with the reshaping of intestinal microecology. Front Pharmacol. 2022;13:893561,1-19.DOI: 10.3389/fphar.2022.893561.
Lee C, Kim J, Wang S, Sung S, Kim N, Lee HH, et al. Hepatoprotective effect of kombucha tea in rodent model of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. Int J Mol Sci. 2019;20(9):2369,1-18.DOI: 10.3390/ijms20092369.
Majumder S, Ghosh A, Chakraborty S, Bhattacharya M. Withdrawal of stimulants from tea infusion by SCOBY during kombucha fermentation: a biochemical investigation. Int J Food Ferment Tech. 2020;10(1):21-26.DOI: 2277-9396.01.2020.5.
Wang Z, Ahmad W, Zhu A, Geng W, Kang W, Ouyang Q, et al. Identification of volatile compounds and metabolic pathway during ultrasound-assisted kombucha fermentation by HS-SPME-GC/MS combined with metabolomic analysis. Ultrason Sonochem. 2023;94:106339,1-16.DOI: 10.1016/j.ultsonch.2023.106339.
Cardoso RR, Neto RO, dos Santos D'Almeida CT, do Nascimento TP, Pressete CG, Azevedo L, et al. Kombuchas from green and black teas have different phenolic profile, which impacts their antioxidant capacities, antibacterial and antiproliferative activities. Food Res Int. J. 2020;128:108782,1-10.DOI: 10.1016/j.foodres.2019.108782.
Jakubczyk K, Kałduńska J, Kochman J, Janda K. Chemical profile and antioxidant activity of the kombucha beverage derived from white, green, black and red tea. Antioxidants. 2020;9(5):447,1-15.DOI: 10.3390/antiox9050447.
La Torre C, Fazio A, Caputo P, Plastina P, Caroleo MC, Cannataro R, et al. Effects of long-term storage on radical scavenging properties and phenolic content of kombucha from black tea. Molecules. 2021;26(18):5474,1-14.DOI: 10.3390/molecules26185474.
Oliveira JT, da Costa FM, da Silva TG, Simões GD, dos Santos Pereira E, da Costa PQ, et al. Green tea and kombucha characterization: phenolic composition, antioxidant capacity and enzymatic inhibition potential. Food Chem. 2023;408:135206,1-7.DOI: 10.1016/j.foodchem.2022.135206.
Zhou DD, Saimaiti A, Luo M, Huang SY, Xiong RG, Shang A, et al. Fermentation with tea residues enhances antioxidant activities and polyphenol contents in kombucha beverages. Antioxidants. 2022;11(1):155,1-17.DOI: 10.3390/antiox11010155.
Lou D, Fang Q, He Y, Ma R, Wang X, Li H, et al. Oxymatrine alleviates high-fat diet/streptozotocin-induced non-alcoholic fatty liver disease in C57BL/6 J mice by modulating oxidative stress, inflammation and fibrosis. Biomed Pharmacother. 2024;174:116491,1-10.DOI: 10.1016/j.biopha.2024.116491.
Yang Z, Zhang L, Liu J, Chan ASC, Li D. Saponins of tomato extract improve non-alcoholic fatty liver disease by regulating oxidative stress and lipid homeostasis. Antioxidants (Basel). 2023;12(10):1848,1-16.DOI: 10.3390/antiox12101848.
Engin AB, Engin A. Obesity and lipotoxicity. Springer; 2017. pp. 443. DOI: 10.1007/978-3-319-48382-5.
Li Z, Berk M, McIntyre TM, Gores GJ, Feldstein AE. The lysosomal‐mitochondrial axis in free fatty acid-induced hepatic lipotoxicity. Hepatology. 2008;47(5):1495-1503.DOI: 10.1002/hep.22183.
Yu D, Chen G, Pan M, Zhang J, He W, Liu Y, et al. High-fat diet‐induced oxidative stress blocks hepatocyte nuclear factor 4α and leads to hepatic steatosis in mice. J Cell Physiol. 2018;233(6): 4770-4782.DOI: 10.1002/jcp.26270.
Cole BK, Feaver RE, Wamhoff BR, Dash A. Non-alcoholic fatty liver disease (NAFLD) models in drug discovery. Expert Opin Drug Discov. 2018;13(2):193-205.DOI: 10.1080/17460441.2018.1410135.
Wong CM, Marcocci L, Liu L, Suzuki YJ. Cell signaling by protein carbonylation and decarbonylation. Antioxid Redox Signal. 2010;12(3):393-404.DOI: 10.1089/ars.2009.2805.
Wong CM, Zhang Y, Huang Y. Bone morphogenic protein-4-induced oxidant signaling via protein carbonylation for endothelial dysfunction. Free Radic Biol Med. 2014;75:178-190.DOI: 10.1016/j.freeradbiomed.2014.07.035.
Weismann D, Hartvigsen K, Lauer N, Bennett KL, Scholl HP, Issa PC, et al. Complement factor H binds malondialdehyde epitopes and protects from oxidative stress. Nature. 2011;478(7367):76-81.DOI: 10.1038/nature10449.
Kowalska M, Piekut T, Prendecki M, Sodel A, Kozubski W, Dorszewska J. Mitochondrial and nuclear DNA oxidative damage in physiological and pathological
aging. DNA Cell Biol. 2020;39(8):1410-1420.DOI: 10.1089/dna.2019.5347.
Martín-Fernández M, Arroyo V, Carnicero C, Sigüenza R, Busta R, Mora N, et al. Role of oxidative stress and lipid peroxidation in the pathophysiology of NAFLD. Antioxidants. 2022;11(11):2217,1-10.DOI: 10.3390/antiox11112217.
Luo H, Chiang HH, Louw M, Susanto A, Chen D. Nutrient sensing and the oxidative stress response. Trends Endocrinol Metab. 2017;28(6):449-460.DOI: 10.1016/j.tem.2017.02.008.
Meng Y, Liu Y, Fang N, Guo Y. Hepatoprotective effects of Cassia semen ethanol extract on non-alcoholic fatty liver disease in experimental rat. Pharm Biol. 2019;57(1):98-104.DOI: 10.1080/13880209.2019.1568509.
de Freitas Carvalho MM, Lage NN, de Souza Paulino AH, Pereira RR, de Almeida LT, da Silva TF, et al. Effects of açai on oxidative stress, ER stress, and inflammation-related parameters in mice with high-fat diet-fed induced NAFLD. Sci Rep. 2019;9(1):8107,1-11.DOI: 10.1038/s41598-019-44563-y.
Gündüz AM, Demir H, Toprak N, Akdeniz H, Demir C, Arslan A, et al. The effect of computed tomography on oxidative stress level and some antioxidant parameters. Acta Radiol. 2021;62(2): 260-265.DOI: 10.1177/0284185120922135.
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