The therapeutic effect of silymarin in the treatment of nonalcoholic fatty disease: A meta-analysis (PRISMA) of randomized control trials

Sheng Zhong, Yuxiang Fan, Qi Yan, Xingyu Fan, Bo Wu, Yujuan Han, Ying Zhang, Yong Chen, Huimao Zhang, Junqi Niu, Sheng Zhong, Yuxiang Fan, Qi Yan, Xingyu Fan, Bo Wu, Yujuan Han, Ying Zhang, Yong Chen, Huimao Zhang, Junqi Niu

Abstract

Background: Silymarin (SIL) is an active extraction of the silybum marianum, milk thistle, which is an ancient medicinal plant for treatment of various liver diseases for centuries. This study is to assess the therapeutic effect of SIL in the treatment of nonalcoholic fatty liver disease through meta-analysis.

Methods: Published randomized controlled trials (RCTs) were included from electronic databases (PubMed, Embase, Cochrane library, Web of Science, and so forth). Cochrane handbook was applied to evaluate the methodological quality. All statistical analyses were directed by Revman 5.3 software, and statistical significance was defined as P < .05.

Results: Eight RCTs involved 587 patients were included in this study. The results showed that SIL reduced the AST and ALT levels more significantly than the control group (AST UI/L: MD = -6.57; 95% CI, -10.03 to -3.12; P = .0002; ALT UI/L: MD = -9.16; 95% CI, -16.24 to -2.08; P = .01). Compared with other interventions, there were significant differences decreasing AST and ALT levels when SIL was used alone (AST UI/L: MD = -5.44; 95% CI, -8.80 to -2.08; P = .002; ALT UI/L: MD = -5.08; 95% CI, -7.85 to -2.32; P = .0003).

Conclusion: SIL has positive efficacy to reduce transaminases levels in NAFLD patients. SIL can be an encouraging and considerable phytotherapy for NAFLD patients.

Conflict of interest statement

The authors have no conflicts of interest to disclose.

Figures

Figure 1
Figure 1
Flowchart of the study selection.
Figure 2
Figure 2
Forest plot of the AST in the meta-analysis and subgroup analysis. There was a significant difference between the 2 arms (AST UI/L: MD = −6.57; 95% CI, −10.03 to −3.12; P = .002).
Figure 3
Figure 3
Forest plot of the ALT in the meta-analysis and subgroup analysis. There was a significant difference between the 2 arms (ALT UI/L: MD = −9.16; 95% CI, −16.24 to −2.08; P = .01).
Figure 4
Figure 4
(A) Forest plot of TG. There was no significant difference between the 2 arms (P = .78). (B) Forest plot of TC. There was no significant difference between the 2 arms (P = .80).

References

    1. Younossi ZM, Koenig AB, Abdelatif D, et al. Global epidemiology of nonalcoholicfatty liver disease—meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology 2016;64:73–84.
    1. Serfaty L, Lemoinea M. Definition and natural history of metabolic steatosis clinical aspects of NAFLD, NASH and cirrhosis. Diabetes Metab 2008;34(6 pt 2):634–7.
    1. Carr RM, Oranu A, Khungar V. Nonalcoholic fatty liver disease: pathophysiology and management. Gastroenterol Clin North Am 2016;45:639–52.
    1. Paradis V, Zalinski S, Chelbi E, et al. Hepatocellular carcinomas in patients with metabolic syndrome often develop without significant liver fibrosis: a pathological analysis. Hepatology 2009;49:851–9.
    1. Athyros VG, Alexandrides TK, Bilianou H, et al. The use of statins alone, or in combination with pioglitazone and other drugs, for the treatment of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis and related cardiovascular risk. An Expert Panel Statement. Metabolism 2017;71:17–32.
    1. Machado MV, Cortez-Pinto H. Non-invasive diagnosis of non-alcoholic fatty liver disease. A critical appraisal. J Hepatol 2013;58:1007–19.
    1. Lin HZ, Yang SQ, Chuckaree C, et al. Metformin reverses fatty liver disease in obese, leptin-deficient mice. Nat Med 2000;6:998–1003.
    1. Laurin J, Lindor KD, Crippin JS, et al. Ursodeoxycholic acid or clofibrate in the treatment of non-alcohol-induced steatohepatitis a pilot study. Hepatology 1996;23:1464–7.
    1. Socha P, Horvath A, Vajro P, et al. Pharmacological interventions for nonalcoholic fatty liver disease in adults and in children: a systematic review. J Pediatr Gastroenterol Nutr 2009;48:587–96.
    1. Biedermann D, Vavrikova E, Cvak L, et al. Chemistry of silybin. Nat Prod Rep 2014;31:1138–57.
    1. Solhi H, Ghahremani R, Kazemifar AM, et al. Silymarin in treatment of non-alcoholic steatohepatitis: a randomized clinical trial. Caspian J Intern Med 2014;5:9–12.
    1. Loguercio C, Andreone P, Brisc C, et al. Silybin combined with phosphatidylcholine and vitamin E in patients with nonalcoholic fatty liver disease: a randomized controlled trial. Free Radic Biol Med 2012;52:1658–65.
    1. Hashemi SJ, Hajiani E, Sardabi EH. A placebo-controlled trial of silymarin in patients with nonalcoholic fatty liver. Hepat Mon 2009;9:265–70.
    1. Bai J. Silymarin combined Ganfusheng in the treatment of nonalcoholic fatty hepatitis treatment observation. J China Tradit Chin Med Inf 2011;3:117.
    1. Han M, Wen P, Wen J, et al. Clinical effect of silymarin combined with simvastatin on patients with nonalcoholic steatohepatitis. Chin J Liver Dis (Electronic Version) 2011;3:15–8.
    1. Deng Y, Fan X, Li J. The state of insulin resistance in patients with nonalcoholic fatty liver and the intervention with Gankangyin. Chin J Integr Med 2005;11:117–22.
    1. Hajiaghamohammadi AA, Ziaee A, Oveisi S, et al. Effects of metformin, pioglitazone, and silymarin treatment on non-alcoholic fatty liver disease: a randomized controlled pilot study. Hepat Mon 2012;12:e6099.
    1. Masoodi M. RA, Panahian M, Vojdanian M. Effects of silymarin on reducing liver aminotransferases in patients with nonalcoholic fatty liver diseases. Govaresh 2013;18:181–5.
    1. Aller R, Izaola O, Gómez S, et al. Effect of silymarin plus vitamin E in patients with non-alcoholic fatty liver disease. A randomized clinical pilot study. Eur Rev Med Pharmacol Sci 2015;19:3118–24.
    1. Zelber-Sagi S, Nitzan-Kaluski D, Goldsmith R, et al. Role of leisure-time physical activity in nonalcoholic fatty liver disease: a population-based study. Hepatology 2008;48:1791–8.
    1. Cortez-Pinto H, Jesus L, Barros H, et al. How different is the dietary pattern in non-alcoholic steatohepatitis patients? Clin Nutr 2006;25:816–23.
    1. Bugianesi E, Pagotto U, Manini R, et al. Plasma adiponectin in nonalcoholic fatty liver is related to hepatic insulin resistance and hepatic fat content, not to liver disease severity. J Clin Endocrinol Metab 2005;90:3498–504.
    1. Odegaard JI, Ricardo-Gonzalez RR, Red Eagle A, et al. Alternative M2 activation of Kupffer cells by PPARdelta ameliorates obesity-induced insulin resistance. Cell Metab 2008;7:496–507.
    1. Jager J, Aparicio-Vergara M, Aouadi M. Liver innate immune cells and insulin resistance: the multiple facets of Kupffer cells. J Intern Med 2016;280:209–20.
    1. Velussi M, Cernigoi AM, Ariella DM, et al. Long-term (12 months) treatment with an anti-oxidant drug (silymarin) is effective on hyperinsulinemia, exogenous insulin need and malondialdehyde levels in cirrhotic diabetic patients. J Hepatol 1997;26:871–9.
    1. Hajaghamohammadi AA, Ziaee A, Rafiei R. The efficacy of silymarin in decreasing transaminase activities in nonalcoholic fatty liver disease: a randomized controlled clinical trial. Hepat Mon 2008;8:191–5.
    1. Li HB, Yang YR, Mo ZJ, et al. Silibinin improves palmitate-induced insulin resistance in C2C12 myotubes by attenuating IRS-1/PI3K/Akt pathway inhibition. Braz J Med Biol Res 2015;48:440–6.
    1. Sherif IO, Al-Gayyar MM. Antioxidant, anti-inflammatory and hepatoprotective effects of silymarin on hepatic dysfunction induced by sodium nitrite. Eur Cytokine Netw 2013;24:114–21.
    1. Abdel-Moneim AM, Al-Kahtani MA, El-Kersh MA, et al. Free radical-scavenging, anti-inflammatory/anti-fibrotic and hepatoprotective actions of taurine and silymarin against CCl4 induced rat liver damage. PLoS ONE 2015;10:e0144509.
    1. Vecchione G, Grasselli E, Voci A, et al. Silybin counteracts lipid excess and oxidative stress in cultured steatotic hepatic cells. World J Gastroenterol 2016;22:6016–26.
    1. Serviddio G, Bellanti F, Stanca E, et al. Silybin exerts antioxidant effects and induces mitochondrial biogenesis in liver of rat with secondary biliary cirrhosis. Free Radic Biol Med 2014;73:117–26.
    1. Basiglio CL, Sanchez Pozzi EJ, Mottino AD, et al. Differential effects of silymarin and its active component silibinin on plasma membrane stability and hepatocellular lysis. Chem Biol Interact 2009;179:297–303.
    1. Muriel P, Moreno MG, Hernandez MdC, et al. Resolution of liver fibrosis in chronic CCl4 administration in the rat after discontinuation of treatment: effect of silymarin, silibinin, colchicine and trimethylcolchicinic acid. Basic Clin Pharmacol Toxicol 2005;96:375–80.
    1. Khosravi S, Alavian SM, Zare A, et al. Non-alcoholic fatty liver disease and correlation of serum alanin aminotransferase. Hepat Mon 2011;11:452–8.
    1. Sonsuz A, Basaranoglu M. Relationship between aminotransferase levels and hitopathological findings in patients with NAFLD. Am J Gastroenterol 2000;95:1370–1.
    1. Park HS, Jang JE, Ko MS, et al. Statins increase mitochondrial and peroxisomal fatty acid oxidation in the liver and prevent non-alcoholic steatohepatitis in mice. Diabetes Metab J 2016;40:376–85.
    1. Musso G, Gambino R, Cassader M, et al. A meta-analysis of randomized trials for the treatment of nonalcoholic fatty liver disease. Hepatology 2010;52:79–104.
    1. Krishnan K, Campbell S, Stone WL. High-dosage vitamin e supplementation and all-cause mortality. Ann Intern Med 2005;143:151–2.
    1. Cacciapuoti F, Scognamiglio A, Palumbo R, et al. Silymarin in non alcoholic fatty liver disease. World J Hepatol 2013;5:109–13.

Source: PubMed

Sponsoren und Mitarbeiter

Krankheiten

Drogeninterventionen

3
Abonnieren