Generic placeholder image

Recent Advances in Food, Nutrition & Agriculture

Editor-in-Chief

ISSN (Print): 2772-574X
ISSN (Online): 2772-5758

Research Article

Cynara Cardunculus Flavonoids-rich Fraction Alleviates Liver Injury in Mice Overconsumed Fructose Model

Author(s): Nacera Baali*, Zahia Belloum, Fadila Benayache and Samir Benayache

Volume 15, Issue 1, 2024

Published on: 24 January, 2024

Page: [74 - 82] Pages: 9

DOI: 10.2174/012772574X275103231206050222

Price: $65

Abstract

Background: Non-alcoholic Fatty liver disease (NAFLD) is becoming a major global health burden in the world. Cynara cardunculus is an edible plant growing wild in the North of Algeria. Its potential as a source of health-promoting compounds is still underexplored.

Objectives: This study aimed to explore the preventive effect of Cynara cardunculus (C. cardunculus) on the NAFLD model.

Methods: Total flavonoid contents (TFC) and in vitro antioxidant effects of butanolic (n- BuTOH) and ethyl acetate (EtOAc) fractions on scavenging the ABTS+ radical, inhibition of lipid peroxidation and reducing power proprieties were assessed. The n-ButOH fraction showed the highest TFC and antioxidant capacity in all realized assays. This fraction is used for anti- NAFLD experiments. Adult male Albinos mice were divided into four groups. Group 1 was normal control. Group 2 was watered with 30% of fructose for three weeks to induce the NAFLD model. Group 3 and Group 4 were co-treated with C. cardunculus n-ButOH fractions and Atorvastatin, respectively for three weeks. Blood and livers were collected for biochemical and histological analysis.

Results: The C. cardunculus n-ButOH fractions significantly restored levels of transaminases, triglycerides, cholesterol, LDL, glucose and uric acid. The n-ButOH fraction exerted an improving effect on the body and liver weight and liver index. It also significantly corrected the imbalance in liver MDA and GSH levels. The n-ButOH fractions further ameliorated abnormalities in liver histology through suppression of lipid droplets accumulation.

Conclusion: This research proves that the flavonoid-rich fraction of C. cardunculus has protective activity against high fructose intake in mice via reversing hyperlipidemia and boosting liver antioxidant capacity.

« Previous
Graphical Abstract

[1]
Coronati, M.; Baratta, F.; Pastori, D.; Ferro, D.; Angelico, F.; Del Ben, M. Added fructose in non-alcoholic fatty liver disease and in metabolic syndrome: A narrative Review. Nutrients, 2022, 14(6), 1127.
[http://dx.doi.org/10.3390/nu14061127] [PMID: 35334784]
[2]
Todoric, J.; Di Caro, G.; Reibe, S.; Henstridge, D.C.; Green, C.R.; Vrbanac, A.; Ceteci, F.; Conche, C.; McNulty, R.; Shalapour, S.; Taniguchi, K.; Meikle, P.J.; Watrous, J.D.; Moranchel, R.; Najhawan, M.; Jain, M.; Liu, X.; Kisseleva, T.; Diaz-Meco, M.T.; Moscat, J.; Knight, R.; Greten, F.R.; Lau, L.F.; Metallo, C.M.; Febbraio, M.A.; Karin, M. Fructose stimulated de novo lipogenesis is promoted by inflammation. Nat. Metab., 2020, 2(10), 1034-1045.
[http://dx.doi.org/10.1038/s42255-020-0261-2] [PMID: 32839596]
[3]
Muriel, P.; López-Sánchez, P.; Ramos-Tovar, E. Fructose and the liver. Int. J. Mol. Sci., 2021, 22(13), 6969.
[http://dx.doi.org/10.3390/ijms22136969] [PMID: 34203484]
[4]
Federico, A.; Rosato, V.; Masarone, M.; Torre, P.; Dallio, M.; Romeo, M.; Persico, M. The role of fructose in non-alcoholic steatohepatitis: Old relationship and new insights. Nutrients, 2021, 13(4), 1314.
[http://dx.doi.org/10.3390/nu13041314] [PMID: 33923525]
[5]
Kanuri, G.; Spruss, A.; Wagnerberger, S.; Bischoff, S.C.; Bergheim, I.; Bergheim, L. Fructose-induced steatosis in mice: role of plasminogen activator inhibitor-1, microsomal triglyceride transfer protein and NKT cells. Lab. Invest., 2011, 91(6), 885-895.
[http://dx.doi.org/10.1038/labinvest.2011.44] [PMID: 21423135]
[6]
Oppedisano, F.; Muscoli, C.; Musolino, V.; Carresi, C.; Macrì, R.; Giancotta, C.; Bosco, F.; Maiuolo, J.; Scarano, F.; Paone, S.; Nucera, S.; Zito, M.C.; Scicchitano, M.; Ruga, S.; Ragusa, M.; Palma, E.; Tavernese, A.; Mollace, R.; Bombardelli, E.; Mollace, V. The protective effect of Cynara cardunculus extract in dietinduced NAFLD: involvement of OCTN1 and OCTN2 transporter subfamily. Nutrients, 2020, 12(5), 1435.
[http://dx.doi.org/10.3390/nu12051435] [PMID: 32429274]
[7]
Acquaviva, R.; Malfa, G.A.; Santangelo, R.; Bianchi, S.; Pappalardo, F.; Taviano, M.F.; Miceli, N.; Di Giacomo, C.; Tomasello, B. Wild Artichoke (Cynara cardunculus subsp. sylvestris, Asteraceae) leaf extract: Phenolic profile and oxidative stress inhibitory effects on HepG2 cells. Molecules, 2023, 28(6), 2475.
[http://dx.doi.org/10.3390/molecules28062475] [PMID: 36985448]
[8]
Ferro, Y.; Maurotti, S.; Mazza, E.; Pujia, R.; Sciacqua, A.; Musolino, V.; Mollace, V.; Pujia, A.; Montalcini, T. Citrus Bergamia and Cynara Cardunculus reduce serum uric acid in individuals with non-alcoholic fatty liver disease. Medicina, 2022, 58(12), 1728.
[http://dx.doi.org/10.3390/medicina58121728] [PMID: 36556930]
[9]
Erikel, E.; Yuzbasioglu, D.; Unal, F. In vitro genotoxic and antigenotoxic effects of cynarin. J. Ethnopharmacol., 2019, 237, 171-181.
[http://dx.doi.org/10.1016/j.jep.2019.03.036] [PMID: 30890359]
[10]
de Sá, F.V.; Barbosa, M. Cheese-making with a vegetable rennet from Cardo (Cynara cardunculus). J. Dairy Res., 1972, 39(3), 335-343.
[http://dx.doi.org/10.1017/S0022029900014163]
[11]
Adzet, T.; Camarasa, J.; Laguna, J.C. Hepatoprotective activity of polyphenolic compounds from Cynara scolymus against CCl4 toxicity in isolated rat hepatocytes. J. Nat. Prod., 1987, 50(4), 612-617.
[http://dx.doi.org/10.1021/np50052a004] [PMID: 3430163]
[12]
Baali, N.; Belloum, Z.; Menad, A.; Ameedah, S.; Benayache, F.; Benayache, S. Antioxidant and protective effect of Cynara cardunculus against paracetamol induced liver mitochondria oxidative stress. Int. J. Phytomed., 2014, 6(4), 601-607.
[13]
Fuhr, L.; Basti, A.; Brás, T.S.; Duarte, M.F.; Relógio, A. Antiproliferative effects of Cynara Cardunculus in colorectal cancer cells are modulated by the circadian clock. Int. J. Mol. Sci., 2022, 23(16), 9130.
[http://dx.doi.org/10.3390/ijms23169130] [PMID: 36012399]
[14]
Rondanelli, M.; Riva, A.; Petrangolini, G.; Allegrini, P.; Bernardinelli, L.; Fazia, T.; Peroni, G.; Gasparri, C.; Nichetti, M.; Faliva, M.A.; Naso, M.; Perna, S. The metabolic effects of Cynara supplementation in overweight and obese class i subjects with newly detected impaired fasting glycemia: A double-blind, placebocontrolled, randomized clinical trial. Nutrients, 2020, 12(11), 3298.
[http://dx.doi.org/10.3390/nu12113298] [PMID: 33126534]
[15]
Maiuolo, J.; Mollace, R.; Bosco, F.; Scarano, F.; Oppedisano, F.; Nucera, S.; Ruga, S.; Guarnieri, L.; Macri, R.; Bava, I.; Carresi, C.; Gliozzi, M.; Musolino, V.; Cardamone, A.; Coppoletta, A.R.; Barillaro, A.; Simari, V.; Salvemini, D.; Palma, E.; Mollace, V. The phytochemical synergistic properties of combination of bergamot polyphenolic fraction and Cynara cardunculus Extract in non-alcoholic fatty liver disease. Agriculture, 2023, 13(2), 249.
[http://dx.doi.org/10.3390/agriculture13020249]
[16]
Barbosa, C.H.; Andrade, M.A.; Vilarinho, F.; Castanheira, I.; Fernando, A.L.; Loizzo, M.R.; Sanches Silva, A. A New insight on Cardoon: Exploring new uses besides cheese making with a view to zero waste. Foods, 2020, 9(5), 564.
[http://dx.doi.org/10.3390/foods9050564] [PMID: 32370268]
[17]
Ben Salem, M.; Ben Abdallah Kolsi, R.; Dhouibi, R.; Ksouda, K.; Charfi, S.; Yaich, M.; Hammami, S.; Sahnoun, Z.; Zeghal, K.M.; Jamoussi, K.; Affes, H. Protective effects of Cynara scolymus leaves extract on metabolic disorders and oxidative stress in alloxan-diabetic rats. BMC Complement. Altern. Med., 2017, 17(1), 328.
[http://dx.doi.org/10.1186/s12906-017-1835-8] [PMID: 28629341]
[18]
Gebhardt, R.; Fausel, M. Antioxidant and hepatoprotective effects of artichoke extracts and constituents in cultured rat hepatocytes. Toxicol. In vitro, 1997, 11(5), 669-672.
[http://dx.doi.org/10.1016/S0887-2333(97)00078-7] [PMID: 20654368]
[19]
Deng, A.; Liu, F.; Tang, X.; Wang, Y.; Xie, P.; Yang, Q.; Xiao, B. Water extract from artichoke ameliorates high-fat diet-induced non-alcoholic fatty liver disease in rats. BMC Complementary Medicine and Therapies, 2022, 22(1), 308.
[http://dx.doi.org/10.1186/s12906-022-03794-9] [PMID: 36424606]
[20]
Llorach, R.; Espín, J.C.; Tomás-Barberán, F.A.; Ferreres, F. Artichoke (Cynara scolymus L.) byproducts as a potential source of health-promoting antioxidant phenolics. J. Agric. Food Chem., 2002, 50(12), 3458-3464.
[http://dx.doi.org/10.1021/jf0200570] [PMID: 12033811]
[21]
Poor, R.Y.; Abdollahi, M.; Malekirad, A.A.; Movahednia, E.; Mostafalou, S.; Sheybani Asl, Z. Effects of the mixture of Cynara cardunculus var scolymus and Cinnamomum zeylanicum on hepatic enzymes activity and lipid profiles in patients with nonalcoholic fatty liver disease. J. Adv. Med. Med. Res., 2019, 29(6), 1-5.
[http://dx.doi.org/10.9734/jammr/2019/v29i630096]
[22]
Alkushi, A. Biological effect of Cynara cardunculus on kidney status of hypercholesterolemic rats. Pharmacogn. Mag., 2017, 13(51), 430.
[http://dx.doi.org/10.4103/pm.pm_14_17] [PMID: 29142395]
[23]
Rangboo, V.; Noroozi, M.; Zavoshy, R.; Rezadoost, S.A.; Mohammadpoorasl, A. The effect of Artichoke leaf extract on alanine Aminotransferase and aspartate aminotransferase in the patients with nonalcoholic steatohepatitis. Int. J. Hepatol., 2016, 2016, 1-6.
[http://dx.doi.org/10.1155/2016/4030476] [PMID: 27293900]
[24]
Bao, J.; Cai, Y.; Sun, M.; Wang, G.; Corke, H. Anthocyanins, flavonols, and free radical scavenging activity of Chinese bayberry (Myrica rubra) extracts and their color properties and stability. J. Agric. Food Chem., 2005, 53(6), 2327-2332.
[http://dx.doi.org/10.1021/jf048312z] [PMID: 15769176]
[25]
Khan, R.A.; Khan, M.R.; Sahreen, S.; Ahmed, M. Evaluation of phenolic contents and antioxidant activity of various solvent extracts of Sonchus asper (L.) Hill. Chem. Cent. J., 2012, 6(1), 12-18.
[http://dx.doi.org/10.1186/1752-153X-6-12] [PMID: 22305477]
[26]
Hattori, M.; Yang, X.W.; Miyashiro, H.; Namba, T. Inhibitory effects of monomeric and dimeric phenylpropanoids from mace on lipid peroxidation in vivo and in vitro. Phytother. Res., 1993, 7(6), 395-401.
[http://dx.doi.org/10.1002/ptr.2650070603]
[27]
Morales, G.; Paredes, A. Antioxidant activities of Lampaya medicinalis extracts and their main chemical constituents. BMC Complement. Altern. Med., 2014, 14(1), 259.
[http://dx.doi.org/10.1186/1472-6882-14-259] [PMID: 25047047]
[28]
Ojha, P.S.; Biradar, P.R.; Tubachi, S.; Patil, V.S. Evaluation of neuroprotective effects of Canna indica L against aluminium chloride induced memory impairment in rats. ADTM, 2023, 23(2), 539-556.
[http://dx.doi.org/10.1007/s13596-021-00627-x]
[29]
Lastuvkova, H.; Faradonbeh, F.A.; Schreiberova, J.; Hroch, M.; Mokry, J.; Faistova, H.; Nova, Z.; Hyspler, R.; Igreja Sa, I.C.; Nachtigal, P.; Stefela, A.; Pavek, P.; Micuda, S. A statin modulates bile acid homeostasis in mice with diet-induced nonalcoholic steatohepatitis. Int. J. Mol. Sci., 2021, 22(12), 6468.
[http://dx.doi.org/10.3390/ijms22126468] [PMID: 34208774]
[30]
Choi, Y.; Abdelmegeed, M.A.; Song, B.J. Diet high in fructose promotes liver steatosis and hepatocyte apoptosis in C57BL/6J female mice: Role of disturbed lipid homeostasis and increased oxidative stress. Food Chem. Toxicol., 2017, 103, 111-121.
[http://dx.doi.org/10.1016/j.fct.2017.02.039] [PMID: 28257781]
[31]
Kouam, A.F.; Yuan, F.; Njayou, F.N.; He, H.; Tsayem, R.F.; Oladejo, B.O.; Song, F.; Moundipa, P.F.; Gao, G.F. Induction of mkp-1 and nuclear translocation of Nrf2 by limonoids from Khaya grandifoliola protect L-02 hepatocytes against acetaminopheninduced hepatotoxicity. Front. Pharmacol., 2017, 8, 653.
[http://dx.doi.org/10.3389/fphar.2017.00653] [PMID: 28974930]
[32]
Ellman, G.L. Tissue sulfhydryl groups. Arch. Biochem. Biophys., 1959, 82(1), 70-77.
[http://dx.doi.org/10.1016/0003-9861(59)90090-6] [PMID: 13650640]
[33]
Thiruvengadam, M.; Venkidasamy, B.; Subramanian, U.; Samynathan, R.; Ali Shariati, M.; Rebezov, M.; Girish, S.; Thangavel, S.; Dhanapal, A.R.; Fedoseeva, N.; Lee, J.; Chung, I.M. Bioactive compounds in oxidative stress-mediated diseases: Targeting the NRF2/ARE signaling pathway and epigenetic regulation. Antioxidants, 2021, 10(12), 1859.
[http://dx.doi.org/10.3390/antiox10121859] [PMID: 34942962]
[34]
Nguyen, Q.T.; Vo Thi, K.H.; Le Van, T.; Nguyen, T.M.T.; Tran Quang, H. Extraction of cynarine and chlorogenic acid from Artichoke leaves (Cynara scolymus L.) and evaluation of antioxidant activity, antibacterial activity of extract. Vietnam J. Chem., 2022, 60(5), 571-577.
[35]
Brown, J.E.; Rice-Evans, C.A. Luteolin-rich artichoke extract protects low density lipoprotein from oxidation In vitro. Free Radic. Res., 1998, 29(3), 247-255.
[http://dx.doi.org/10.1080/10715769800300281] [PMID: 9802556]
[36]
Hernández-Díazcouder, A.; Romero-Nava, R.; Carbó, R.; Sánchez-Lozada, L.G.; Sánchez-Muñoz, F. High fructose intake and adipogenesis. Int. J. Mol. Sci., 2019, 20(11), 2787.
[http://dx.doi.org/10.3390/ijms20112787] [PMID: 31181590]
[37]
Baali, N.; Belloum, Z.; Baali, S.; Chabi, B.; Pessemesse, L.; Fouret, G.; Ameddah, S.; Benayache, F.; Benayache, S.; Feillet-Coudray, C.; Cabello, G.; Wrutniak-Cabello, C. protective activity of total polyphenols from Genista quadriflora Munby and Teucrium polium geyrii Maire in acetaminophen-induced hepatotoxicity in rats. Nutrients, 2016, 8(4), 193.
[http://dx.doi.org/10.3390/nu8040193] [PMID: 27043622]
[38]
Geidl-Flueck, B.; Gerber, P.A. Fructose drives de novo lipogenesis affecting metabolic health. J. Endocrinol., 2023, 257(2), e220270.
[http://dx.doi.org/10.1530/JOE-22-0270] [PMID: 36753292]
[39]
Hassan, M.D.; Abdulkarim, Z.I.; Mary, M. Effect of Balanites aegyptiaca fruit-pericarp extract on fructose induced hyperglycemia and hyperlipidemia in rats. Asian. J. Biotechnol., 2020, 12, 87-96.
[40]
Turkiewicz, I.; Wojdyło, A.; Tkacz, K.; Nowicka, P.; Hernández, F. Antidiabetic, anticholinesterase and antioxidant activity vs. terpenoids and phenolic compounds in selected new cultivars and hybrids of Artichoke Cynara scolymus L. Molecules, 2019, 24(7), 1222.
[http://dx.doi.org/10.3390/molecules24071222] [PMID: 30925771]
[41]
Kuczmannová, A.; Balažová, A.; Račanská, E.; Kameníková, M.; Fialová, S.; Majerník, J.; Nagy, M.; Gál, P.; Mučaji, P. Agrimonia eupatoria L. and Cynara cardunculus L. water infusions: Comparison of anti-diabetic activities. Molecules, 2016, 21(5), 564.
[http://dx.doi.org/10.3390/molecules21050564] [PMID: 27136516]
[42]
Kalvandi, R.; Rajabi, M.; Kahramfar, Z.; Chaleh Cheleh, T. Investigation of the effect of Artichoke (cynara scolymus L.) on characteristics of the fatty liver. Complementary Medicine Journal, 2020, 10(2), 134-147.
[http://dx.doi.org/10.32598/cmja.10.2.891.1]
[43]
Pérez-García, F.; Adzet, T.; Cañigueral, S. Activity of artichoke leaf extract on reactive oxygen species in human leukocytes. Free Radic. Res., 2000, 33(5), 661-665.
[http://dx.doi.org/10.1080/10715760000301171] [PMID: 11200096]
[44]
Jiménez-Moreno, N.; Cimminelli, M.J.; Volpe, F.; Ansó, R.; Esparza, I.; Mármol, I.; Rodríguez-Yoldi, M.J.; Ancín-Azpilicueta, C. phenolic composition of artichoke waste and its antioxidant capacity on differentiated Caco-2 cells. Nutrients, 2019, 11(8), 1723.
[http://dx.doi.org/10.3390/nu11081723] [PMID: 31349733]
[45]
Cicero, A.F.G.; Colletti, A.; Bajraktari, G.; Descamps, O.; Djuric, D.M.; Ezhov, M.; Fras, Z.; Katsiki, N.; Langlois, M.; Latkovskis, G.; Panagiotakos, D.B.; Paragh, G.; Mikhailidis, D.P.; Mitchenko, O.; Paulweber, B.; Pella, D.; Pitsavos, C.; Reiner, Ž.; Ray, K.K.; Rizzo, M.; Sahebkar, A.; Serban, M.C.; Sperling, L.S.; Toth, P.P.; Vinereanu, D.; Vrablík, M.; Wong, N.D.; Banach, M. Lipid lowering nutraceuticals in clinical practice: Position paper from an International Lipid Expert Panel. Arch. Med. Sci., 2017, 5(5), 965-1005.
[http://dx.doi.org/10.5114/aoms.2017.69326] [PMID: 28883839]
[46]
Mass, B.; Nance, B.; Voruganti, S. Fructose increases the expression of uric acid-induced oxidative stress genes, nox4 and foxo3, in cultured HepG2 cells. Curr. Dev. Nutr., 2020, 4(Suppl. 2)
[http://dx.doi.org/10.1093/cdn/nzaa058_024]
[47]
Madlala, H.P.; Maarman, G.J.; Ojuka, E. Uric acid and transforming growth factor in fructose-induced production of reactive oxygen species in skeletal muscle. Nutr. Rev., 2016, 74(4), 259-266.
[http://dx.doi.org/10.1093/nutrit/nuv111] [PMID: 26946251]
[48]
Roškarić, P.; Šperanda, M.; Mašek, T.; Verbanac, D.; Starčević, K. Low dietary n6/n3 ratio attenuates changes in the NRF 2 gene expression, lipid peroxidation, and inflammatory markers induced by fructose overconsumption in the rat abdominal adipose tissue. Antioxidants, 2021, 10(12), 2005.
[http://dx.doi.org/10.3390/antiox10122005] [PMID: 34943108]
[49]
Lee, M.; Kim, D.; Park, S.J.; Kim, K.S.; Park, G.D.; Kim, O.K.; Lee, J. lee, J. Artichoke extract directly suppresses inflammation and apoptosis in hepatocytes during the development of nonalcoholic fatty liver disease. J. Med. Food, 2021, 24(10), 1083-1091.
[http://dx.doi.org/10.1089/jmf.2021.K.0069] [PMID: 34591699]
[50]
Musolino, V.; Gliozzi, M.; Bombardelli, E.; Nucera, S.; Carresi, C.; Maiuolo, J.; Mollace, R.; Paone, S.; Bosco, F.; Scarano, F.; Scicchitano, M.; Macrì, R.; Ruga, S.; Zito, M.C.; Palma, E.; Gratteri, S.; Ragusa, M.; Volterrani, M.; Fini, M.; Mollace, V. The synergistic effect of Citrus bergamia and Cynara cardunculus extracts on vascular inflammation and oxidative stress in nonalcoholic fatty liver disease. J. Tradit. Complement. Med., 2020, 10(3), 268-274.
[http://dx.doi.org/10.1016/j.jtcme.2020.02.004] [PMID: 32670822]
[51]
Liao, G.C.; Jhuang, J.H.; Yao, H.T. Artichoke leaf extract supplementation lowers hepatic oxidative stress and inflammation and increases multidrug resistance-associated protein 2 in mice fed a high-fat and high-cholesterol diet. Food Funct., 2021, 12(16), 7239-7249.
[http://dx.doi.org/10.1039/D1FO00861G] [PMID: 34165128]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy