1. Introduction

Fatty liver is one of the most important causes of chronic liver disease in humans. Non-alcoholic fatty liver disease is a disease that has a wide range of clinical symptoms and, if left untreated, can eventually lead to liver cell cancer and death [1, 2]. Many serum enzymes have been suggested for detecting liver cell degradation, of which Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) are of particular importance [9].

Therapeutic effects of the artichoke plant (Cynara scolymus L.) include liver supportive, antimicrobial, cholesterol-lowering and lipid-lowering effects, stimulation of nitric oxide synthetase gene expression, and stimulation and improvement of endothelial cells in atherosclerosis healing [16]. In this study, the use of Artichoke as a suitable treatment for fatty liver disease without the mentioned complications was investigated.

2. Materials and Methods

This study is a randomized non-blind clinical trial based on informed consent and no placebo. The statistical population in this study was the patients referred to Imam Khomeini Hospital in Hamadan. Artichoke plant was prepared from the garden of medicinal plants of Bu-Ali Sina in Hamedan. The parts used in this plant were dried, in the shade, ground, and powdered. Then, the required number was packaged and they were asked to brew and drink a tablespoon of plant leaves with a glass of boiling water twice a day for 20 minutes on indirect heat for 20 minutes, 45 days.

At the end of this study, the results of ultrasound and blood tests of 70 people were finally analyzed. Data collection tools included a questionnaire and ultrasound and personal and demographic information of the samples, condition, and severity of fatty liver and symptoms and comorbidities were completed by the subjects. Finally, the collected data were analyzed by SPSS V. 22 software. Paired t-test was also used to compare the means.

3. Results

The results showed that the Mean±SD age of the subjects was 47.46±12.10 and patients between the ages of 46-60 had the highest frequency (45.7%) (Table 1).



The Mean±SD of weight and height of the subjects were 76.83±16.70 and 166.56±24.65, respectively. Most of the subjects were female (47=67.1%), with primary literacy (n=28; 40%), and with housekeeping as occupation (n=44; 62.9%) were. The results showed that the Mean±SD of the patients’ enzymes measured before and after using the Artichoke plant for ALT enzyme was 52.49±26.76 and 36.96±13.01 (P≤0.005). These values for AST enzyme were: 41.20±14.46 and 31.76±14.46 (P≤0.005), respectively (Table 1).

Based on the results of sonography, 51 patients (72.86%) showed a decrease in the degree or grade of fatty liver (P≤0.01). The mean total grade of fatty liver decreased from 1.67 to 1.0 (Figure 1).



Also, the amount of sugar decreased from 111.58 (before treatment) to 103.58 (after treatment) and cholesterol decreased from 209.28 (before treatment) to 151.23 (after treatment), which as a result of consumption of this plant during 45 days showed a significant decrease (P≤0.045 and P≤0.007, respectively). Triglyceride also decreased from 185.81 to 164.81 which showed no significant changes (Table 1). The results showed that with increasing the amount of blood cholesterol, the Grade of fatty liver also increased (Figure 2).

 4. Discussion

The results of the study showed that the drinking of Artichoke tea can be effective in reducing the grade of fatty liver. Many studies have shown that the compounds in plants’ extracts can prevent toxic effects on the liver and reduce liver enzymes, which is consistent with the results of the present study. 

The prevalence of fatty liver in women (67.1%) in this study was about twice that of men (32.9%). Also, Savadkoohi et al. reported that the rate of fatty liver among women is 3.5 times higher than men, which is consistent with the results of this study [26]. The results also showed that the rate of reduction of the grade of fatty liver and thus improving the effects of fatty liver in women was more than men, which is probably as a result of the subjects’ occupation (housewives, 67.3%), who usually on time in drinking herbal tea. According to traditional medicine experts, women are more prone to fatty liver than men due to their cold temper and phlegmatic temperament.

On the other hand, lowering blood sugar, triglyceride, and cholesterol levels showed the positive effects of this plant in reducing and improving liver function and treatment of hyperlipidemia [35]. Studies have shown that this plant reduces lipids and lipoproteins by interfering with the biosynthesis of cholesterol and also affects the production and secretion of bile in the liver. They have also indicated that this plant reduces lipids and lipoproteins by interfering with the biosynthesis of cholesterol and also affects the production and secretion of bile in the liver. It seems that the existence of flavonoid compounds in this plant is responsible for its effects, especially in improving liver’s function [40, 41].

5. Conclusion

The results of this clinical trial study showed that it seems that this plant can be used to improve the laboratory symptoms of fatty liver; moreover, can be used as a herbal supplement, with no significant side effects, in reducing the complications of this disease.

Ethical Considerations

Compliance with ethical guidelines

This study approved by the Vice Chancellor for Education of Hamadan University of Medical Sciences (Code: No.4785/9/35/16/ and dated: 10/3/1493); and this research is a clinical trial conducted by the Iranian Clinical Trial website (Code: RCT20130126012278N3).

Funding

This study did not receive any specific assistance from funding agencies in the public, commercial, or private sectors.

Authors' contributions

Conceptualization, research method and sampling: Zohreh Kahramofar, Tahereh Chaleh Chaleh; Data analysis, article writing and review: Mohsen Rajabi; Project supervision and management: Ramadan Klondi. 

Conflicts of interest

The authors declared no conflict of interest.

Acknowledgements

We hereby thank the Deputy for Education of Hamadan University of Medical Sciences and the Ethics Committee, and also the officials of the Iranian Clinical Trial Site for registering this research.

 

References

1.Khan RS, Bril F, Cusi K, Newsome PN. Modulation of insulin resistance in Nonalcoholic Fatty Liver Disease. Hepatology. 2019; 70(2):711‐24. [DOI:10.1002/hep.30429] [PMID]

2.Lonardo A, Nascimbeni F, Maurantonio M, Marrazzo A, Rinaldi L, Adinolfi LE. Nonalcoholic fatty liver disease: Evolving paradigms. World Journal of Gastroenterology. 2017; 23(36):6571-92. [DOI:10.3748/wjg.v23.i36.6571] [PMID] [PMCID]

3.Bellentani S. The epidemiology of non-alcoholic fatty liver disease. Liver International. 2017; 37 Suppl 1:81-4. [DOI:10.1111/liv.13299] [PMID]

4.Barikani A, Pashaeypoor Sh. [Lifestyle in non-alcoholic fatty liver: A review (Persian)]. Iranian Journal of Nursing Research. 2019; 13(6):39-47. http://ijnr.ir/article-1-2215-en.html

5.Oliveira CP, de Lima Sanches P, de Abreu-Silva EO, Marcadenti A. Nutrition and physical activity in nonalcoholic fatty liver disease. Journal of Diabetes Research. 2016; 2016:4597246. [DOI:10.1155/2016/4597246] [PMID] [PMCID]

6.Contos MJ, Sanyal AJ. The clinicopathologic spectrum and management of nonalcoholic fatty liver disease. Advances in Anatomic Pathology. 2002; 9(1):37-51. [DOI:10.1097/00125480-200201000-00005] [PMID]

7.Angulo P. Nonalcoholic fatty liver disease. The New England Journal of Medicine. 2002; 346(16):1221-31. [DOI:10.1056/NEJMra011775] [PMID]

8.Neuschwander-Tetri BA, Caldwell SH. Nonalcoholic Steatohepatitis: Summary of an AASLD single topic conference. Hepatology. 2003; 37(5):1202-19. [DOI:10.1053/jhep.2003.50193] [PMID]

9.Foreston WC, Tedesco FJ, Starnes EC, Shaw CT. Marked elevation of serum transaminase activity associated with extrahepatic biliary tract disease. Journal of Clinical Gastroenterology. 1985; 7(6):502-5. [DOI:10.1097/00004836-198512000-00012] [PMID]

10.Dongiovanni P, Lanti C, Riso P, Valenti L. Nutritional therapy for nonalcoholic fatty liver disease. The Journal of Nutritional Biochemistry. 2016; 29:1-11. [DOI:10.1016/j.jnutbio.2015.08.024] [PMID]

11.Kobyliak N, Virchenko O, Falalyeyeva T, Kondro M, Beregova T, Bodnar P, et al. Cerium dioxide nanoparticles possess anti-inflammatory properties in the conditions of the obesity-associated NAFLD in rats. Biomedicine & Pharmacotherapy. 2017; 90:608-14. [DOI:10.1016/j.biopha.2017.03.099] [PMID]

12.Ahmed IA, Mikail MA. Paradigm shift: Focusing on plant-based natural antimicrobials. Journal of Microbiology & Experimentation. 2017; 5(2):00145. [DOI:10.15406/ jmen.2017.05.00145.]

13.Sanyal AJ, Chalasani N, Kowdley KV, McCullough A, Diehl AM, Bass NM, et al. Pioglitazone, vitamin E, or placebo for nonalcoholic Steatohepatitis. The New England Journal of Medicine. 2010; 362(18):1675-85. [DOI:10.1056/NEJMoa0907929] [PMID] [PMCID]

14.Zhu X, Zhang H, Lo R. Phenolic compounds from the leaf extract of artichoke (Cynara scolymus L.) and their antimicrobial activities. Journal of Agricultural and Food Chemistry. 2004; 52(24):7272-8. [DOI:10.1021/jf0490192] [PMID]

15.Li H, Xia N, Brausch I, Yao Y, Forstermann U. Flavonoids from artichoke (Cynara scolymus L.) up-regulate endothelial-type nitric-oxide synthase gene expression in human endothelial cells. Journal of Pharmacology and Experimental Therapeutics. 2004; 310(3):926-32. [DOI:10.1124/jpet.104.066639] [PMID]

16.Lupattelli G, Marchesi S, Lombardini R, Roscini AR, Trinca F, Gemelli F, et al. Artichoke juice improves endothelial function in hyperlipemia. Life Sciences. 2004; 76(7):775-82. [DOI:10.1016/j.lfs.2004.07.018] [PMID]

17.Wittemer SM, Ploch M, Windeck T, Müller SC, Drewelow B, Derendorf H, et al. Bioavilability and pharmacokinetics of caffeoylquinic acids and flavonoids after oral administration of artichoke leaf extracts in humans. Phytomedicine. 2005; 12(1-2):28-38. [DOI:10.1016/j.phymed.2003.11.002] [PMID]

18.Yan H, Gao YQ, Zhang Y, Wang H, Liu GS, Lei JY. Chlorogenic acid alleviates autophagy and insulin resistance by suppressing JNK pathway in a rat model of nonalcoholic fatty liver disease. Journal of Biosciences. 2018; 43(2):287-94. [DOI:10.1007/s12038-018-9746-5] [PMID]

19.Blumenthal M, Goldberg A, Brinckmann J. Herbal medicine: Expanded commission E monographs. Newton, MA: Integrative Medicine Communications; 2000. 

20.Sambaiah K, Srinivasan K. Influence of spices and spice principles on hepatic mixed function oxygenase system in rats. Indian Journal of Biochemistry & Biophysics. 1989; 26(4):254-8. [PMID]

21.Aggarwal R, Nagi M, Kochhar A. Effect of nutrition education on blood glucose and lipid profile of non insulin dependent female diabetics. Journal of Human Ecology. 2007; 22(4):323-6. [DOI:10.1080/09709274.2007.11906042]

22.Thomas CMG, Bastiaans LA, Rolland R. Effects of prostaglandin F2α, lndomethacin, and estradiol on ovum transport and pregnancy in the golden hamster. Biology of Reproduction. 1980; 23(4):687-98. [DOI:10.1095/biolreprod23.4.687] [PMID]

23.Schütz K, Kammerer D, Carle R, Schieber A. Identification and quantification of caffeoylquinic acids and flavonoids from artichoke (Cynara scolymus L.) heads, juice, and pomace by HPLC-DAD-ESI/MSn. Journal of Agricultural and Food Chemistry. 2004; 52(13):4090-6. [DOI:10.1021/jf049625x] [PMID]

24.Iranikhah A, Shapouri J, Heidari A, Aghaali M, Hajian H. [Effects of silymarin on nonalcoholic fatty liver disease in children: A crossover clinical trial (Persian)]. Journal of Mazandaran University of Medical Sciences. 2017; 26(144):119-26. http://jmums.mazums.ac.ir/article-1-9244-en.html

25.Khalili M, Sahraee H, Hassanpour Ezati M. [Anti-inflammatory effect of alcoholic stinging nettle extract in male NMRI rats (Persian)]. Journal of Medicinal Plants. 2007; 6(22):46-53. http://jmp.ir/article-1-615-en.html

26.Savadkoohi F, Hosseini Tabatabaei SMT, Shahabi Nezhad S. [The frequency of fatty liver in sonography of patients without liver diseases background and its correlation with blood cholesterol and triglyceride (Persian)]. Zahedan Journal of Research in Medical Sciences. 2003; 5(3):177-83. https://www.sid.ir/fa/journal/ViewPaper.aspx?ID=15476

27.Romero-Gómez M, Zelber-Sagi Sh, Trenell M. Treatment of NAFLD with diet, physical activity and exercise. Journal of Hepatology. 2017; 67(4):829-46. [DOI:10.1016/j.jhep.2017.05.016] [PMID]

28.Pourshams A, Malekzadeh R, Monavvari A, Akbari MR, Mohamadkhani A, Yarahmadi Sh, et al. Prevalence and etiology of persistently elevated alanine aminotransferase levels in healthy Iranian blood donors. Journal of Gastroenterology & Hepatology. 2005; 20(2):229-33. [DOI:10.1111/j.1440-1746.2004.03511.x] [PMID]

29.Moradi Kelardeh B, Azarbayjani MA, Peeri M, Matin Homaee H. [Effect of curcumin supplementation and resistance training in patients with nonalcoholic fatty liver disease (Persian)]. Journal of Medicinal Plants. 2016; 15(60):161-72. http://jmp.ir/article-1-1511-en.html

30.Moradi Kohnaki Z, Asadollahi Kh, Abangah Gh, Sayehmiri K. [Risk factors of nonalcoholic fatty liver disease: A case-control study (Persian)]. Tehran University Medical Journal. 2016; 74(9):645-56. http://tumj.tums.ac.ir/article-1-7808-en.html

31.Eslahi M, Mohammadifar M, Taghizadeh M, Khamechian T, Mehran M, Talaei SAR. [Effects of Ziziphus jujube Mill., Cynara scolymus L. and Cichorium intybus L. combination extract on non-alcoholic fatty liver disease in rats (Persian)]. Koomesh. 2018; 20(4):741-7. http://koomeshjournal.semums.ac.ir/article-1-4312-en.html

32.Rahimlou M, Yari Z, Hekmatdoost A, Alavian SA, Keshavarz SA. [Effect of ginger supplementation on liver enzymes, hepatic fibrosis and steatosis in nonalcoholic fatty liver disease: A double blind randomized-controlled clinical trial (Persian)]. Iranian Journal of Nutrition Sciences & Food Technology. 2016; 11(2):1-8. http://nsft.sbmu.ac.ir/article-1-2008-en.html

33.Jun DW. [The role of diet in non-alcoholic fatty liver disease (Korean)]. The Korean Journal of Gastroenterology. 2013; 61(5):243-51. [DOI:10.4166/kjg.2013.61.5.243] [PMID]

34.Da Silva HE, Arendt BM, Noureldin SA, Therapondos G, Guindi M, Allard JP. A cross-sectional study assessing dietary intake and physical activity in Canadian patients with nonalcoholic fatty liver disease vs healthy controls. Journal of the Academy of Nutrition and Dietetics. 2014; 114(8):1181-94. [DOI:10.1016/j.jand.2014.01.009] [PMID]

35.Heidarian E, Soofiniya Y, Hajihosseini R. [The effect of aerial part of Cynara scolymus extract on the hyperlipidemia, plasma antioxidant capacity, and superoxide dismutase activity in diabetic rats (Persian)]. Journal of Shahrekord University of Medical Sciences. 2011; 13(5):1-9. http://journal.skums.ac.ir/article-1-912-en.html

36.Sahbayi Ejlali E. [Comparing the effect of combined extract of Fumaria parviflora, Salix aegyptiaca, Taraxacum officinale ,Coriandrum sativum L versus Vit E on liver enzymes level in patients with fatty liver disease (Persian)] [MD. thesis]. Sabzevar: Sabzevar University of Medical Sciences; 2017. https://fa.irct.ir/trial/27025

37.Wider B, Pittler MH, Thompson-Coon J, Ernst E. Artichoke leaf extract for treating hypercholesterolemia. The Cochrane Database of Systematic Reviews. 2009; (4):CD003335. [DOI:10.1002/14651858.CD003335.pub2] [PMID]

38.Bonyadi F, Tukmechi A, Mohebalian H. [An overview of probiotics and their role in cancer management (Persian)]. Journal of Mazandaran University of Medical Sciences. 2014; 24(112):128-40. http://jmums.mazums.ac.ir/article-1-3122-en.html

39.Dehghan P, Miwechi M, Izadi E, Mohammadi F, Sohrabi MR. [Comparison of nutritional behaviors and body mass index in patients with and without non-alcoholic fatty liver disease (Persian)]. Commun Health. 2015; 1(2):81-8. https://www.sid.ir/fa/Journal/ViewPaper.aspx?id=248716

40.Salehisahlabadi A, Khoshgoftar M, Asadi E, Jadidi H. [The prevalence of non-alcoholic fatty liver disease in Iranian children and adolescents: A systematic review and meta-analysis (Persian)]. Journal of Sabzevar University of Medical Sciences. 2018; 25(4):486-94. http://jsums.medsab.ac.ir/article_1094_en.html