Effects of different natural products in patients with non-alcoholic fatty liver disease-A network meta-analysis of randomized controlled trials.

Publisher: Wiley Country of Publication: England NLM ID: 8904486 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1099-1573 (Electronic) Linking ISSN: 0951418X NLM ISO Abbreviation: Phytother Res Subsets: MEDLINE

Publication: : Chichester : Wiley
Original Publication: London : Heyden & Son, c1987-

Non-alcoholic Fatty Liver Disease*/drug therapy ; Randomized Controlled Trials as Topic* ; Network Meta-Analysis* ; Plant Extracts*/pharmacology ; Plant Extracts*/therapeutic use; Humans ; Biological Products/therapeutic use ; Biological Products/pharmacology ; Aspartate Aminotransferases/blood ; Alanine Transaminase/blood ; Cynara scolymus/chemistry ; Cholesterol, LDL/blood ; Plant Leaves/chemistry

Due to a scarcity of appropriate therapeutic approaches capable of ameliorating or eliminating non-alcoholic fatty liver disease (NAFLD), many researchers have come to focus on natural products based on traditional medicine that can be utilized to successfully treat NAFLD. In this study, we aimed to evaluate the effects exerted by seven natural products (curcumin, silymarin, resveratrol, artichoke leaf extract, berberine, catechins, and naringenin) on patients with NAFLD. For this purpose, PubMed, Embase, Cochrane Library, and Web of Science, were searched for randomized controlled trials (RCTs) exclusively. The selected studies were evaluated for methodological quality via the Cochrane bias risk assessment tool, and data analysis software was used to analyze the data accordingly. The RCTs from the earliest available date until September 2022 were collected. This process resulted in 37 RCTs with a total sample size of 2509 patients being included. The results of the network meta-analysis showed that artichoke leaf extract confers a relative advantage in reducing the aspartate aminotransferase (AST) levels (SUCRA: 99.1%), alanine aminotransferase (ALT) levels (SUCRA: 88.2%) and low-density lipoprotein cholesterol (LDL-C) levels (SUCRA: 88.9%). Naringenin conferred an advantage in reducing triglyceride (TG) levels (SUCRA: 97.3%), total cholesterol (TC) levels (SUCRA: 73.9%), and improving high-density lipoprotein cholesterol (HDL-C) levels (SUCRA: 74.9%). High-density catechins significantly reduced body mass index (BMI) levels (SUCRA: 98.5%) compared with the placebo. The Ranking Plot of the Network indicated that artichoke leaf extract and naringenin performed better than the other natural products in facilitating patient recovery. Therefore, we propose that artichoke leaf extract and naringenin may exert a better therapeutic effect on NAFLD. This study may help guide clinicians and lead to further detailed studies.
(© 2024 John Wiley & Sons Ltd.)

Anushiravani, A., Haddadi, N., Pourfarmanbar, M., & Mohammadkarimi, V. (2019). Treatment options for nonalcoholic fatty liver disease: A double‐blinded randomized placebo‐controlled trial. European Journal of Gastroenterology & Hepatology, 31(5), 613–617. https://doi.org/10.1097/MEG.0000000000001369.
Asghari, S., Asghari‐Jafarabadi, M., Somi, M. H., Ghavami, S. M., & Rafraf, M. (2018). Comparison of calorie‐restricted diet and resveratrol supplementation on anthropometric indices, metabolic parameters, and serum Sirtuin‐1 levels in patients with nonalcoholic fatty liver disease: A randomized controlled clinical trial. Journal of the American College of Nutrition, 37(3), 223–233. https://doi.org/10.1080/07315724.2017.1392264.
Assini, J. M., Mulvihill, E. E., Burke, A. C., Sutherland, B. G., Telford, D. E., Chhoker, S. S., Sawyez, C. G., Drangova, M., Adams, A. C., Kharitonenkov, A., Pin, C. L., & Huff, M. W. (2015). Naringenin prevents obesity, hepatic steatosis, and glucose intolerance in male mice independent of fibroblast growth factor 21. Endocrinology, 156(6), 2087–2102. https://doi.org/10.1210/en.2014-2003.
Azzini, E., Bugianesi, R., Romano, F., di Venere, D., Miccadei, S., Durazzo, A., Foddai, M. S., Catasta, G., Linsalata, V., & Maiani, G. (2007). Absorption and metabolism of bioactive molecules after oral consumption of cooked edible heads of Cynara scolymus L. (cultivar Violetto di Provenza) in human subjects: A pilot study. The British Journal of Nutrition, 97(5), 963–969. https://doi.org/10.1017/S0007114507617218.
Burke, A. C., Telford, D. E., Edwards, J. Y., Sutherland, B. G., Sawyez, C. G., & Huff, M. W. (2019). Naringenin supplementation to a chow diet enhances energy expenditure and fatty acid oxidation, and reduces adiposity in lean, pair‐fed Ldlr−/− mice. Molecular Nutrition & Food Research, 63(6), e1800833. https://doi.org/10.1002/mnfr.201800833.
Chachay, V. S., Macdonald, G. A., Martin, J. H., Whitehead, J. P., O'Moore‐Sullivan, T. M., Lee, P., Franklin, M., Klein, K., Taylor, P. J., Ferguson, M., Coombes, J. S., Thomas, G. P., Cowin, G. J., Kirkpatrick, C. M., Prins, J. B., & Hickman, I. J. (2014). Resveratrol does not benefit patients with nonalcoholic fatty liver disease. Clinical Gastroenterology and Hepatology, 12(12), 2092–103.e1036. https://doi.org/10.1016/j.cgh.2014.02.024.
Chaimani, A., Higgins, J. P., Mavridis, D., Spyridonos, P., & Salanti, G. (2013). Graphical tools for network meta‐analysis in STATA. PLoS One, 8(10), e76654. https://doi.org/10.1371/journal.pone.0076654.
Chan, C. Y., Wei, L., Castro‐Muñozledo, F., & Koo, W. L. (2011). (−)‐Epigallocatechin‐3‐gallate blocks 3T3‐L1 adipose conversion by inhibition of cell proliferation and suppression of adipose phenotype expression. Life Sciences, 89(21–22), 779–785. https://doi.org/10.1016/j.lfs.2011.09.006.
Chang, W. C., Jia, H., Aw, W., Saito, K., Hasegawa, S., & Kato, H. (2014). Beneficial effects of soluble dietary Jerusalem artichoke (Helianthus tuberosus) in the prevention of the onset of type 2 diabetes and non‐alcoholic fatty liver disease in high‐fructose diet‐fed rats. The British Journal of Nutrition, 112(5), 709–717. https://doi.org/10.1017/S0007114514001421.
Chashmniam, S., Mirhafez, S. R., Dehabeh, M., Hariri, M., Azimi Nezhad, M., & Gh, B. F. N. M. (2019). A pilot study of the effect of phospholipid curcumin on serum metabolomic profile in patients with non‐alcoholic fatty liver disease: A randomized, double‐blind, placebo‐controlled trial. European Journal of Clinical Nutrition, 73(9), 1224–1235. https://doi.org/10.1038/s41430-018-0386-5.
Chatrath, H., Vuppalanchi, R., & Chalasani, N. (2012). Dyslipidemia in patients with nonalcoholic fatty liver disease. Seminars in Liver Disease, 32(1), 22–29. https://doi.org/10.1055/s-0032-1306423.
Chen, S., Zhao, X., Ran, L., Wan, J., Wang, X., Qin, Y., Shu, F., Gao, Y., Yuan, L., Zhang, Q., & Mi, M. (2015). Resveratrol improves insulin resistance, glucose and lipid metabolism in patients with non‐alcoholic fatty liver disease: A randomized controlled trial. Digestive and Liver Disease, 47(3), 226–232. https://doi.org/10.1016/j.dld.2014.11.015.
Chinetti, G., Lestavel, S., Bocher, V., Remaley, A. T., Neve, B., Torra, I. P., Teissier, E., Minnich, A., Jaye, M., Duverger, N., Brewer, H. B., Fruchart, J. C., Clavey, V., & Staels, B. (2001). PPAR‐alpha and PPAR‐gamma activators induce cholesterol removal from human macrophage foam cells through stimulation of the ABCA1 pathway. Nature Medicine, 7(1), 53–58. https://doi.org/10.1038/83348.
Cho, K. W., Kim, Y. O., Andrade, J. E., Burgess, J. R., & Kim, Y. C. (2011). Dietary naringenin increases hepatic peroxisome proliferators‐activated receptor α protein expression and decreases plasma triglyceride and adiposity in rats. European Journal of Nutrition, 50(2), 81–88. https://doi.org/10.1007/s00394-010-0117-8.
Cicero, A. F. G., Sahebkar, A., Fogacci, F., Bove, M., Giovannini, M., & Borghi, C. (2020). Effects of phytosomal curcumin on anthropometric parameters, insulin resistance, cortisolemia and non‐alcoholic fatty liver disease indices: A double‐blind, placebo‐controlled clinical trial. European Journal of Nutrition, 59(2), 477–483. https://doi.org/10.1007/s00394-019-01916-7.
Colletta, C., Colletta, A., & Placentino, G. (2020). Lifestyle and silymarin: A fight against liver damage in NAFLD associated‐prediabetic disease. Journal of Diabetes and Metabolic Disorders, 19(2), 883–894. https://doi.org/10.1007/s40200-020-00576-3.
Dabravolski, S. A., Bezsonov, E. E., Baig, M. S., Popkova, T. V., & Orekhov, A. N. (2021). Mitochondrial lipid homeostasis at the crossroads of liver and heart diseases. International Journal of Molecular Sciences, 22(13), 6949. https://doi.org/10.3390/ijms22136949.
Faghihzadeh, F., Adibi, P., & Hekmatdoost, A. (2015). The effects of resveratrol supplementation on cardiovascular risk factors in patients with non‐alcoholic fatty liver disease: A randomised, double‐blind, placebo‐controlled study. The British Journal of Nutrition, 114(5), 796–803. https://doi.org/10.1017/S0007114515002433.
Faghihzadeh, F., Adibi, P., Rafiei, R., & Hekmatdoost, A. (2014). Resveratrol supplementation improves inflammatory biomarkers in patients with nonalcoholic fatty liver disease. Nutrition Research (New York, N.Y.), 34(10), 837–843. https://doi.org/10.1016/j.nutres.2014.09.005.
Farzin, L., Asghari, S., Rafraf, M., Asghari‐Jafarabadi, M., & Shirmohammadi, M. (2020). No beneficial effects of resveratrol supplementation on atherogenic risk factors in patients with nonalcoholic fatty liver disease. International Journal for Vitamin and Nutrition Research. Internationale Zeitschrift Fur Vitamin‐ Und Ernahrungsforschung. Journal International de Vitaminologie et de Nutrition, 90(3–4), 279–289. https://doi.org/10.1024/0300-9831/a000528.
Ference, B. A., Ginsberg, H. N., Graham, I., Ray, K. K., Packard, C. J., Bruckert, E., Hegele, R. A., Krauss, R. M., Raal, F. J., Schunkert, H., Watts, G. F., Borén, J., Fazio, S., Horton, J. D., Masana, L., Nicholls, S. J., Nordestgaard, B. G., van de Sluis, B., Taskinen, M. R., … Catapano, A. L. (2017). Low‐density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European atherosclerosis society consensus panel. European Heart Journal, 38(32), 2459–2472. https://doi.org/10.1093/eurheartj/ehx144.
Friedman, S. L., Neuschwander‐Tetri, B. A., Rinella, M., & Sanyal, A. J. (2018). Mechanisms of NAFLD development and therapeutic strategies. Nature Medicine, 24(7), 908–922. https://doi.org/10.1038/s41591-018-0104-9.
Goldwasser, J., Cohen, P. Y., Yang, E., Balaguer, P., Yarmush, M. L., & Nahmias, Y. (2010). Transcriptional regulation of human and rat hepatic lipid metabolism by the grapefruit flavonoid naringenin: Role of PPARalpha, PPARgamma and LXRalpha. PLoS One, 5(8), e12399. https://doi.org/10.1371/journal.pone.0012399.
Grattagliano, I., Portincasa, P., Palmieri, V. O., & Palasciano, G. (2007). Managing nonalcoholic fatty liver disease: Recommendations for family physicians. Canadian family physician Medecin de famille canadien, 53(5), 857–863.
Guerre‐Millo, M., Gervois, P., Raspé, E., Madsen, L., Poulain, P., Derudas, B., Herbert, J. M., Winegar, D. A., Willson, T. M., Fruchart, J. C., Berge, R. K., & Staels, B. (2000). Peroxisome proliferator‐activated receptor alpha activators improve insulin sensitivity and reduce adiposity. The Journal of Biological Chemistry, 275(22), 16638–16642. https://doi.org/10.1074/jbc.275.22.16638.
Hajiaghamohammadi, A. A., Ziaee, A., Oveisi, S., & Masroor, H. (2012). Effects of metformin, pioglitazone, and silymarin treatment on non‐alcoholic fatty liver disease: A randomized controlled pilot study. Hepatitis Monthly, 12(8), e6099. https://doi.org/10.5812/hepatmon.6099.
Hariri, M., Gholami, A., Mirhafez, S. R., Bidkhori, M., & Sahebkar, A. (2020). A pilot study of the effect of curcumin on epigenetic changes and DNA damage among patients with non‐alcoholic fatty liver disease: A randomized, double‐blind, placebo‐controlled, clinical trial. Complementary Therapies in Medicine, 51, 102447. https://doi.org/10.1016/j.ctim.2020.102447.
Heebøll, S., Kreuzfeldt, M., Hamilton‐Dutoit, S., Kjær Poulsen, M., Stødkilde‐Jørgensen, H., Møller, H. J., Jessen, N., Thorsen, K., Kristina Hellberg, Y., Bønløkke Pedersen, S., & Grønbæk, H. (2016). Placebo‐controlled, randomised clinical trial: High‐dose resveratrol treatment for non‐alcoholic fatty liver disease. Scandinavian Journal of Gastroenterology, 51(4), 456–464. https://doi.org/10.3109/00365521.2015.1107620.
Hermenean, A., Ardelean, A., Stan, M., Hadaruga, N., Mihali, C. V., Costache, M., & Dinischiotu, A. (2014). Antioxidant and hepatoprotective effects of naringenin and its β‐cyclodextrin formulation in mice intoxicated with carbon tetrachloride: A comparative study. Journal of Medicinal Food, 17(6), 670–677. https://doi.org/10.1089/jmf.2013.0007.
Hernández‐Aquino, E., & Muriel, P. (2018). Beneficial effects of naringenin in liver diseases: Molecular mechanisms. World Journal of Gastroenterology, 24(16), 1679–1707. https://doi.org/10.3748/wjg.v24.i16.1679.
Hernández‐Aquino, E., Zarco, N., Casas‐Grajales, S., Ramos‐Tovar, E., Flores‐Beltrán, R. E., Arauz, J., Shibayama, M., Favari, L., Tsutsumi, V., Segovia, J., & Muriel, P. (2017). Naringenin prevents experimental liver fibrosis by blocking TGFβ‐Smad3 and JNK‐Smad3 pathways. World Journal of Gastroenterology, 23(24), 4354–4368. https://doi.org/10.3748/wjg.v23.i24.4354.
Higgins, J. P., Altman, D. G., Gøtzsche, P. C., Jüni, P., Moher, D., Oxman, A. D., Savovic, J., Schulz, K. F., Weeks, L., Sterne, J. A., & Cochrane Bias Methods Group, & Cochrane Statistical Methods Group. (2011). The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ (Clinical Research Ed.), 343, d5928. https://doi.org/10.1136/bmj.d5928.
Jackson, D., Riley, R., & White, I. R. (2011). Multivariate meta‐analysis: Potential and promise. Statistics in Medicine, 30(20), 2481–2498. https://doi.org/10.1002/sim.4172.
Jarhahzadeh, M., Alavinejad, P., Farsi, F., Husain, D., & Rezazadeh, A. (2021). The effect of turmeric on lipid profile, malondialdehyde, liver echogenicity and enzymes among patients with nonalcoholic fatty liver disease: A randomized double blind clinical trial. Diabetology & Metabolic Syndrome, 13(1), 112. https://doi.org/10.1186/s13098-021-00731-7.
Jazayeri‐Tehrani, S. A., Rezayat, S. M., Mansouri, S., Qorbani, M., Alavian, S. M., Daneshi‐Maskooni, M., & Hosseinzadeh‐Attar, M. J. (2019). Nano‐curcumin improves glucose indices, lipids, inflammation, and Nesfatin in overweight and obese patients with non‐alcoholic fatty liver disease (NAFLD): A double‐blind randomized placebo‐controlled clinical trial. Nutrition and Metabolism, 16, 8. https://doi.org/10.1186/s12986-019-0331-1.
Kantartzis, K., Fritsche, L., Bombrich, M., Machann, J., Schick, F., Staiger, H., Kunz, I., Schoop, R., Lehn‐Stefan, A., Heni, M., Peter, A., Fritsche, A., Häring, H. U., & Stefan, N. (2018). Effects of resveratrol supplementation on liver fat content in overweight and insulin‐resistant subjects: A randomized, double‐blind, placebo‐controlled clinical trial. Diabetes, Obesity & Metabolism, 20(7), 1793–1797. https://doi.org/10.1111/dom.13268.
Karamfilova, V., Gateva, A., Assyov, Y., Alexiev, A., Savov, A., Yaneva, N., Ivanova, I., Ivanova‐Boyanova, R., Ivanova, R., Vlahova, Z., Mateva, L., & Kamenov, Z. (2019). PNPLA3 I148M polymorphism in patients with nonalcoholic fatty liver disease, obesity and prediabetes. Journal of Gastrointestinal and Liver Diseases: JGLD, 28(4), 433–438. https://doi.org/10.15403/jgld-506.
Khera, R., Murad, M. H., Chandar, A. K., Dulai, P. S., Wang, Z., Prokop, L. J., Loomba, R., Camilleri, M., & Singh, S. (2016). Association of pharmacological treatments for obesity with weight loss and adverse events: A systematic review and meta‐analysis. JAMA, 315(22), 2424–2434. https://doi.org/10.1001/jama.2016.7602.
Kim, H., Hiraishi, A., Tsuchiya, K., & Sakamoto, K. (2010). (−) Epigallocatechin gallate suppresses the differentiation of 3T3‐L1 preadipocytes through transcription factors FoxO1 and SREBP1c. Cytotechnology, 62(3), 245–255. https://doi.org/10.1007/s10616-010-9285-x.
Lee, M., Kim, D., Park, S. J., Kim, K. S., Park, G. D., Kim, O. K., & Lee, J. (2021). Artichoke extract directly suppresses inflammation and apoptosis in hepatocytes during the development of non‐alcoholic fatty liver disease. Journal of Medicinal Food, 24(10), 1058–1067. https://doi.org/10.1089/jmf.2021.K.0069.
Li, D., & Chen, P. (2021). Effects of aquatic exercise and land‐based exercise on cardiorespiratory fitness, motor function, balance, and functional Independence in stroke patients‐a meta‐analysis of randomized controlled trials. Brain Sciences, 11(8), 1097. https://doi.org/10.3390/brainsci11081097.
Lin, H. J., Ku, K. L., Lin, I. H., & Yeh, C. C. (2017). Naringenin attenuates hepatitis B virus X protein‐induced hepatic steatosis. BMC Complementary and Alternative Medicine, 17(1), 505. https://doi.org/10.1186/s12906-017-2019-2.
Marotta, N., Demeco, A., Moggio, L., Marinaro, C., Pino, I., Barletta, M., Petraroli, A., Pepe, D., Lavano, F., & Ammendolia, A. (2020). Comparative effectiveness of breathing exercises in patients with chronic obstructive pulmonary disease. Complementary Therapies in Clinical Practice, 41, 101260. https://doi.org/10.1016/j.ctcp.2020.101260.
Matsui, T., Yoshimoto, C., Osajima, K., Oki, T., & Osajima, Y. (1996). In vitro survey of alpha‐glucosidase inhibitory food components. Bioscience, Biotechnology, and Biochemistry, 60(12), 2019–2022. https://doi.org/10.1271/bbb.60.2019.
Mirhafez, S. R., Azimi‐Nezhad, M., Dehabeh, M., Hariri, M., Naderan, R. D., Movahedi, A., Abdalla, M., Sathyapalan, T., & Sahebkar, A. (2021). The effect of curcumin Phytosome on the treatment of patients with non‐alcoholic fatty liver disease: A double‐blind, randomized, placebo‐controlled trial. Advances in Experimental Medicine and Biology, 1308, 25–35. https://doi.org/10.1007/978-3-030-64872-5_3.
Mirhafez, S. R., Dehabeh, M., Hariri, M., Farimani, A. R., Movahedi, A., Naderan, R. D., Jamialahmadi, T., Simental‐Mendía, L. E., & Sahebkar, A. (2021). Curcumin and piperine combination for the treatment of patients with non‐alcoholic fatty liver disease: A double‐blind randomized placebo‐controlled trial. Advances in Experimental Medicine and Biology, 1328, 11–19. https://doi.org/10.1007/978-3-030-73234-9_2.
Mirhafez, S. R., Farimani, A. R., Dehhabe, M., Bidkhori, M., Hariri, M., Ghouchani, B. F., & Abdollahi, F. (2019). Effect of Phytosomal curcumin on circulating levels of adiponectin and leptin in patients with non‐alcoholic fatty liver disease: A randomized, double‐blind, placebo‐controlled clinical trial. Journal of Gastrointestinal and Liver Diseases: JGLD, 28, 183–189. https://doi.org/10.15403/jgld-179.
Mirhafez, S. R., Rezai, A., Dehabeh, M., Gh, B. F. N. M., Bidkhori, M., Sahebkar, A., & Hariri, M. (2021). Efficacy of phytosomal curcumin among patients with non‐alcoholic fatty liver disease. International Journal for Vitamin and Nutrition Research. Internationale Zeitschrift Fur Vitamin‐ Und Ernahrungsforschung. Journal International de Vitaminologie et de Nutrition, 91(3–4), 278–286. https://doi.org/10.1024/0300-9831/a000629.
Mirhashemi, S. H., Hakakzadeh, A., Yeganeh, F. E., Oshidari, B., & Rezaee, S. P. (2022). Effect of 8 Weeks milk thistle powder (silymarin extract) supplementation on fatty liver disease in patients candidates for bariatric surgery. Metabolism Open, 14, 100190. https://doi.org/10.1016/j.metop.2022.100190.
Moher, D., Shamseer, L., Clarke, M., Ghersi, D., Liberati, A., Petticrew, M., Shekelle, P., Stewart, L. A., & PRISMA‐P Group. (2015). Preferred reporting items for systematic review and meta‐analysis protocols (PRISMA‐P) 2015 statement. Systematic Reviews, 4(1), 1. https://doi.org/10.1186/2046-4053-4-1.
Moon, H. S., Chung, C. S., Lee, H. G., Kim, T. G., Choi, Y. J., & Cho, C. S. (2007). Inhibitory effect of (−)‐epigallocatechin‐3‐gallate on lipid accumulation of 3T3‐L1 cells. Obesity (Silver Spring, Md.), 15(11), 2571–2582. https://doi.org/10.1038/oby.2007.309.
Murase, T., Nagasawa, A., Suzuki, J., Hase, T., & Tokimitsu, I. (2002). Beneficial effects of tea catechins on diet‐induced obesity: Stimulation of lipid catabolism in the liver. International Journal of Obesity and Related Metabolic Disorders, 26(11), 1459–1464. https://doi.org/10.1038/sj.ijo.0802141.
Nakai, M., Fukui, Y., Asami, S., Toyoda‐Ono, Y., Iwashita, T., Shibata, H., Mitsunaga, T., Hashimoto, F., & Kiso, Y. (2005). Inhibitory effects of oolong tea polyphenols on pancreatic lipase in vitro. Journal of Agricultural and Food Chemistry, 53(11), 4593–4598. https://doi.org/10.1021/jf047814+.
Namkhah, Z., Naeini, F., Mahdi Rezayat, S., Yaseri, M., Mansouri, S., & Javad Hosseinzadeh‐Attar, M. (2021). Does naringenin supplementation improve lipid profile, severity of hepatic steatosis and probability of liver fibrosis in overweight/obese patients with NAFLD? A randomised, double‐blind, placebo‐controlled, clinical trial. International Journal of Clinical Practice, 75(11), e14852. https://doi.org/10.1111/ijcp.14852.
Navekar, R., Rafraf, M., Ghaffari, A., Asghari‐Jafarabadi, M., & Khoshbaten, M. (2017). Turmeric supplementation improves serum glucose indices and leptin levels in patients with nonalcoholic fatty liver diseases. Journal of the American College of Nutrition, 36(4), 261–267. https://doi.org/10.1080/07315724.2016.1267597.
Orhan, I. E., Nabavi, S. F., Daglia, M., Tenore, G. C., Mansouri, K., & Nabavi, S. M. (2015). Naringenin and atherosclerosis: A review of literature. Current Pharmaceutical Biotechnology, 16(3), 245–251. https://doi.org/10.2174/1389201015666141202110216.
Panahi, Y., Kianpour, P., Mohtashami, R., Atkin, S. L., Butler, A. E., Jafari, R., Badeli, R., & Sahebkar, A. (2018). Efficacy of artichoke leaf extract in non‐alcoholic fatty liver disease: A pilot double‐blind randomized controlled trial. Phytotherapy Research: PTR, 32(7), 1382–1387. https://doi.org/10.1002/ptr.6073.
Panahi, Y., Kianpour, P., Mohtashami, R., Jafari, R., Simental‐Mendía, L. E., & Sahebkar, A. (2016). Curcumin lowers serum lipids and uric acid in subjects with nonalcoholic fatty liver disease: A randomized controlled trial. Journal of Cardiovascular Pharmacology, 68(3), 223–229. https://doi.org/10.1097/FJC.0000000000000406.
Panahi, Y., Kianpour, P., Mohtashami, R., Jafari, R., Simental‐Mendía, L. E., & Sahebkar, A. (2017). Efficacy and safety of Phytosomal curcumin in non‐alcoholic fatty liver disease: A randomized controlled trial. Drug Research, 67(4), 244–251. https://doi.org/10.1055/s-0043-100019.
Panahi, Y., Valizadegan, G., Ahamdi, N., Ganjali, S., Majeed, M., & Sahebkar, A. (2019). Curcuminoids plus piperine improve nonalcoholic fatty liver disease: A clinical trial. Journal of Cellular Biochemistry, 120(9), 15989–15996. https://doi.org/10.1002/jcb.28877.
Rahmani, S., Asgary, S., Askari, G., Keshvari, M., Hatamipour, M., Feizi, A., & Sahebkar, A. (2016). Treatment of non‐alcoholic fatty liver disease with curcumin: A randomized placebo‐controlled trial. Phytotherapy Research: PTR, 30(9), 1540–1548. https://doi.org/10.1002/ptr.5659.
Rangboo, V., Noroozi, M., Zavoshy, R., Rezadoost, S. A., & Mohammadpoorasl, A. (2016). The effect of artichoke leaf extract on alanine aminotransferase and aspartate aminotransferase in the patients with nonalcoholic Steatohepatitis. International Journal of Hepatology, 2016, 4030476. https://doi.org/10.1155/2016/4030476.
Ren, B., Qin, W., Wu, F., Wang, S., Pan, C., Wang, L., Zeng, B., Ma, S., & Liang, J. (2016). Apigenin and naringenin regulate glucose and lipid metabolism, and ameliorate vascular dysfunction in type 2 diabetic rats. European Journal of Pharmacology, 773, 13–23. https://doi.org/10.1016/j.ejphar.2016.01.002.
Rouse, B., Chaimani, A., & Li, T. (2017). Network meta‐analysis: An introduction for clinicians. Internal and Emergency Medicine, 12(1), 103–111. https://doi.org/10.1007/s11739-016-1583-7.
Saadati, S., Hatami, B., Yari, Z., Shahrbaf, M. A., Eghtesad, S., Mansour, A., Poustchi, H., Hedayati, M., Aghajanpoor‐Pasha, M., Sadeghi, A., & Hekmatdoost, A. (2019). The effects of curcumin supplementation on liver enzymes, lipid profile, glucose homeostasis, and hepatic steatosis and fibrosis in patients with non‐alcoholic fatty liver disease. European Journal of Clinical Nutrition, 73(3), 441–449. https://doi.org/10.1038/s41430-018-0382-9.
Saadati, S., Sadeghi, A., Mansour, A., Yari, Z., Poustchi, H., Hedayati, M., Hatami, B., & Hekmatdoost, A. (2019). Curcumin and inflammation in non‐alcoholic fatty liver disease: A randomized, placebo controlled clinical trial. BMC Gastroenterology, 19(1), 133. https://doi.org/10.1186/s12876-019-1055-4.
Saberi‐Karimian, M., Keshvari, M., Ghayour‐Mobarhan, M., Salehizadeh, L., Rahmani, S., Behnam, B., Jamialahmadi, T., Asgary, S., & Sahebkar, A. (2020). Effects of curcuminoids on inflammatory status in patients with non‐alcoholic fatty liver disease: A randomized controlled trial. Complementary Therapies in Medicine, 49, 102322. https://doi.org/10.1016/j.ctim.2020.102322.
Sahebkar, A., Pirro, M., Banach, M., Mikhailidis, D. P., Atkin, S. L., & Cicero, A. F. G. (2018). Lipid‐lowering activity of artichoke extracts: A systematic review and meta‐analysis. Critical Reviews in Food Science and Nutrition, 58(15), 2549–2556. https://doi.org/10.1080/10408398.2017.1332572.
Sakata, R., Nakamura, T., Torimura, T., Ueno, T., & Sata, M. (2013). Green tea with high‐density catechins improves liver function and fat infiltration in non‐alcoholic fatty liver disease (NAFLD) patients: A double‐blind placebo‐controlled study. International Journal of Molecular Medicine, 32(5), 989–994. https://doi.org/10.3892/ijmm.2013.1503.
Salanti, G., Ades, A. E., & Ioannidis, J. P. (2011). Graphical methods and numerical summaries for presenting results from multiple‐treatment meta‐analysis: An overview and tutorial. Journal of Clinical Epidemiology, 64(2), 163–171. https://doi.org/10.1016/j.jclinepi.2010.03.016.
Salehi, B., Fokou, P. V. T., Sharifi‐Rad, M., Zucca, P., Pezzani, R., Martins, N., & Sharifi‐Rad, J. (2019). The therapeutic potential of Naringenin: A review of clinical trials. Pharmaceuticals (Basel, Switzerland), 12(1), 11. https://doi.org/10.3390/ph12010011.
Santos, H. O., Bueno, A. A., & Mota, J. F. (2018). The effect of artichoke on lipid profile: A review of possible mechanisms of action. Pharmacological Research, 137, 170–178. https://doi.org/10.1016/j.phrs.2018.10.007.
Schütz, K., Kammerer, D., Carle, R., & Schieber, A. (2004). Identification and quantification of caffeoylquinic acids and flavonoids from artichoke (Cynara scolymus L.) heads, juice, and pomace by HPLC‐DAD‐ESI/MS(n). Journal of Agricultural and Food Chemistry, 52(13), 4090–4096. https://doi.org/10.1021/jf049625x.
Solhi, H., Ghahremani, R., Kazemifar, A. M., & Hoseini Yazdi, Z. (2014). Silymarin in treatment of non‐alcoholic steatohepatitis: A randomized clinical trial. Caspian Journal of Internal Medicine, 5(1), 9–12.
Unno, T., Tago, M., Suzuki, Y., Nozawa, A., Sagesaka, Y. M., Kakuda, T., Egawa, K., & Kondo, K. (2005). Effect of tea catechins on postprandial plasma lipid responses in human subjects. The British Journal of Nutrition, 93(4), 543–547. https://doi.org/10.1079/bjn20041379.
van Beek, J. H., de Moor, M. H., de Geus, E. J., Lubke, G. H., Vink, J. M., Willemsen, G., & Boomsma, D. I. (2013). The genetic architecture of liver enzyme levels: GGT, ALT and AST. Behavior Genetics, 43(4), 329–339. https://doi.org/10.1007/s10519-013-9593-y.
Vats, D., Flegal, J. M., & Jones, G. L. (2019). Multivariate output analysis for Markov chain Monte Carlo. Biometrika, 106, 321–337. https://doi.org/10.1093/biomet/asz002.
Wah Kheong, C., Nik Mustapha, N. R., & Mahadeva, S. (2017). A randomized trial of Silymarin for the treatment of nonalcoholic Steatohepatitis. Clinical Gastroenterology and Hepatology, 15(12), 1940–1949.e8. https://doi.org/10.1016/j.cgh.2017.04.016.
Wali, A. F., Rashid, S., Rashid, S. M., Ansari, M. A., Khan, M. R., Haq, N., Alhareth, D. Y., Ahmad, A., & Rehman, M. U. (2020). Naringenin regulates doxorubicin‐induced liver dysfunction: Impact on oxidative stress and inflammation. Plants (Basel, Switzerland), 9(4), 550. https://doi.org/10.3390/plants9040550.
Wallace, B. C., Schmid, C. H., Lau, J., & Trikalinos, T. A. (2009). Meta‐analyst: Software for meta‐analysis of binary, continuous and diagnostic data. BMC Medical Research Methodology, 9, 80. https://doi.org/10.1186/1471-2288-9-80.
Wang, J., Yang, Z., Lin, L., Zhao, Z., Liu, Z., & Liu, X. (2012). Protective effect of naringenin against lead‐induced oxidative stress in rats. Biological Trace Element Research, 146(3), 354–359. https://doi.org/10.1007/s12011-011-9268-6.
Wang, S., Moustaid‐Moussa, N., Chen, L., Mo, H., Shastri, A., Su, R., Bapat, P., Kwun, I., & Shen, C. L. (2014). Novel insights of dietary polyphenols and obesity. The Journal of Nutritional Biochemistry, 25(1), 1–18. https://doi.org/10.1016/j.jnutbio.2013.09.001.
Wittemer, S. M., Ploch, M., Windeck, T., Müller, S. C., Drewelow, B., Derendorf, H., & Veit, M. (2005). Bioavailability and pharmacokinetics of caffeoylquinic acids and flavonoids after oral administration of artichoke leaf extracts in humans. Phytomedicine: International Journal of Phytotherapy and Phytopharmacology, 12(1–2), 28–38. https://doi.org/10.1016/j.phymed.2003.11.002.
Yan, H. M., Xia, M. F., Wang, Y., Chang, X. X., Yao, X. Z., Rao, S. X., Zeng, M. S., Tu, Y. F., Feng, R., Jia, W. P., Liu, J., Deng, W., Jiang, J. D., & Gao, X. (2015). Efficacy of Berberine in patients with non‐alcoholic fatty liver disease. PLoS One, 10(8), e0134172. https://doi.org/10.1371/journal.pone.0134172.
Zhou, F., Zhou, J., Wang, W., Zhang, X. J., Ji, Y. X., Zhang, P., She, Z. G., Zhu, L., Cai, J., & Li, H. (2019). Unexpected rapid increase in the burden of NAFLD in China from 2008 to 2018: A systematic review and meta‐analysis. Hepatology (Baltimore, Md.), 70(4), 1119–1133. https://doi.org/10.1002/hep.30702.
Zusi, C., Mantovani, A., Olivieri, F., Morandi, A., Corradi, M., Miraglia Del Giudice, E., Dauriz, M., Valenti, L., Byrne, C. D., Targher, G., & Maffeis, C. (2019). Contribution of a genetic risk score to clinical prediction of hepatic steatosis in obese children and adolescents. Digestive and Liver Disease, 51(11), 1586–1592. https://doi.org/10.1016/j.dld.2019.05.029.

2013-081 The Science and Technology Development Project of Traditional Chinese Medicine in Shandong Province; 2019-0093 The Science and Technology Development Project of Traditional Chinese Medicine in Shandong Province; (2016)47 National Prestigious Chinese Medicine Doctor Studio of Xinlu Wang Project; 81573945 National Natural Science Foundation of China; 2013GSF11902 the Science and Technology Development Project of Shandong Province; ZR2021MH054 National Natural Science Foundation of Shandong Province

Keywords: NAFLD; RCTs; natural products; network meta‐analysis; patients with non‐alcoholic fatty liver disease

0 (Plant Extracts)
0 (Biological Products)
EC 2.6.1.1 (Aspartate Aminotransferases)
EC 2.6.1.2 (Alanine Transaminase)
0 (Cholesterol, LDL)

Date Created: 20240617 Date Completed: 20240711 Latest Revision: 20240715

20240715

10.1002/ptr.8182

38886838