THE EVALUATION OF HEPATOPROTECTIVE EFFECT OF SILYMARIN, PHYLLANTHUS NIRURI EXTRACT AND CHOLINE COMBINATION
Abstract
The high incidence of liver diseases due to the use of xenobiotics and unhealthy lifestyle is associated with increased need for hepatoprotective product administration. Aim: The hepatoprotective effect of the combination silymarin / Phyllanthus niruri extract / choline was investigated in comparison with silymarin alone in patients with hepatic steatosis, in an open clinical study. Material and methods: 101 patients with non-alcoholic hepatic steatosis confirmed by high values of serum transaminases and ultrasonography were included in the study. The patients were divided into two groups, group A received 150 mg silymarin three times daily, and group B a hepatoprotective complex (120 mg silymarin / 225 mg Phyllanthus niruri extract / 60 mg choline) three times daily, for 6 months. The hepatoprotective effects were assessed through the evolution of the following laboratory parameters: aspartate transaminase (AST), alanine transaminase (ALT), gamma-glutamyl transferase (GGT), alkaline phosphatase, serum bilirubin and serum cholesterol at 3 and 6 months after the initiation of the hepatoprotective treatment. Results: Both products were effective in the normalization of liver function, but the combination silymarin / Phyllanthus niruri extract / choline showed significantly better results than silymarin alone, considering the normalization of the hepatic parameter values after 3 and 6 months. The risk for hepatoprotective failure was significantly lower with the combination silymarin / Phyllanthus niruri extract / choline versus silymarin alone, the number needed to treat (NNT) being 3.7 after 3 months and 2.5 after 6 months. Conclusions: The combination silymarin / Phyllanthus niruri extract / choline induced a better liver protection than silymarin alone.
References
2. Cojocariu CE, Trifan AV, Gîrleanu I, Stanciu C. Alcoholic liver disease epidemiology and risk factors. Rev Med Chir Soc Med Nat Iasi 2014; 118(4): 910-917.
3. Radu C, Grigorescu M, Crisan D, Lupsor M, Constantin D, Dina L. Prevalence and associated risk factors of non-alcoholic fatty liver disease in hospitalized patients. J Gastrointestin Liver Dis 2008; 17: 255-260.
4. Iacob S, Ester C, Lita M, Ratziu V, Gheorghe L. Real-life Perception and Practice Patterns of NAFLD / NASH in Romania: Results of a Survey Completed by 102 Board-certified Gastroenterologists. J Gastrointestin Liver Dis 2016; 25(2): 183-189.
5. Livadariu R. et al. Nonalcoholic fatty liver disease and its complications assessing the population at risk. A small series report and literature review. Rev Med Chir Soc Med Nat Iasi 2015; 119(2): 346-352.
6. Hurjui DM et al. Non-alcoholic fatty liver disease is associated with cardiovascular risk factors of metabolic syndrome. Rev Med Chir Soc Med Nat Iasi 2012; 116(3): 692-699.
7. Raman M, Allard J. Non-alcoholic fatty liver disease: a clinical approach and review. Can J Gastro-enterol 2006; 20(5): 345-349.
8. de Avelar CR, Pereira EM, de Farias Costa PR, de Jesus RP, de Oliveira LPM. Effect of silymarin on biochemical indicators in patients with liver disease: Systematic review with meta-analysis. World J Gastroenterol 2017; 23(27): 5004-5017.
9. Ni X, Wang H. Silymarin attenuated hepatic steatosis through regulation of lipid metabolism and oxidative stress in a mouse model of nonalcoholic fatty liver disease (NAFLD). Am J Transl Res 2016; 8(2): 1073-1081.
10. Adedapo A, Ofuegbe S, Adeyemi A. The antidiabetic activities of the methanol leaf extract of Phyl-lanthus amarus in some laboratory animals. As J Med. Sci 2013; 4: 23-34.
11. Odoh UE, Ezugwu CO, Osadebe PO, Ajali U. Preliminary Phytochemical and Hypoglycemic studies on Phyllanthus Niruri (Euphorbiaceae) Leaf Extract. Nigerian J Pharm Res 2010; 8: 78-83.
12. Shetti A, Kaliwal BB. Hypoglycemic activity of ethanolic leaf extract of Phyllanthus amarus in alloxan induced diabetic mice. Europ J Experim Biol 2015; 5: 26-29.
13. Udupa AL. et al.Diuretic activity of Phyllanthus niruri (Linn.) in rats. Health 2010; 2: 511-512.
14. Cacciapuoti F, Scognamiglio A, Palumbo R, Forte R, Cacciapuoti F. Silymarin in non-alcoholic fatty liver disease. World J Hepatol 2013; 5(3): 109-113.
15. Committee on Herbal Medicinal Products. Assessment report on Silybum marianum (L.) Gaertn., fructus. Draft. 2015; EMA / HMPC / 294187 / 2013.
16. Taylor L. Technical Data Report for Chanca Piedra “Stone Breaker” (Phyllanthus niruri). In: Herbal Secrets of the Rainforest, 2nd edition, London, Sage Press, Inc 2003.
17. Bhattacharjee R, Sil PC. The protein fraction of Phyllanthus niruri plays a protective role against acetaminophen induced hepatic disorder via antioxidant properties. Phytoter Res 2006; 20: 595-601.
18. Bhattacharjee R, Sil PC. Protein isolate from the herb, Phyllanthus niruri. (Euphorbiaceae), plays hepatoprotective role against carbon tetrachloride induced liver damage via its antioxidant properties. Food Chem Toxic 2007; 45: 817-826.
19. Roy C, Asad M, Das A, Pillai D. Comparative study of the hepatoprotective efficacy of a few marketed polyherbal products. Pharmacology OnLine 2009; 1: 629-647.
20. Enogieru AB, Charles YO, Omoruyi SI, Momodu OI. Phyllanthus amarus: A hepatoprotective Agent in Acetaminophen induced Liver Toxicity in adult Wistar Rats. SMU Med J 2015; 2: 150-165.
21. Nikam P, Nikam S, Sontakke A, Khanwelkar C. Role of Phyllanthus amarus treatment in Hepatitis-C. Biomed Res 2011; 22: 319-322.
22. Yadav N et al. Synergistic effect of silymarin and standardized extract of Phyllanthus amarus against CCl4-induced hepatotoxicity in Rattus norvegicus. Phytomedicine 2008; 15: 1053-1061.
23. Singh G. Goyal R. Sharma P. Pharmacological potential of silymarin in combination with hepatopro-tective plants against experimental hepatotoxicity in rats. Asian J Pharm Clin Res 2012; 5: 128-133.
24. Dubin MD et al. Choline deficiency: a cause of hepatic steatosis during parenteral nutrition that can be reversed with intravenous choline supplementation. Hepatology 1995; 22: 1399-1403.
25. Guerrerio AL et al. Choline intake in a large cohort of patients with nonalcoholic fatty liver disease. Am J Clin Nutr 2012; 95: 892-900.
26. European Food Safety Authority, Panel on Dietetic Products, Nutrition and Allergies. Scientific opinion on the substantiation of health claims related to choline and contribution to normal lipid metabolism (ID 3186), maintenance of normal liver function (ID 1501), contribution to normal homocysteine metabolism (ID 3090), maintenance of normal neurological function (ID 1502), contribution to normal cognitive function (ID 1502), and brain and neurological development (ID 1503) pursuant to Article 13(1) of Regulation (EC) No 1924 / 2006. EFSA Journal 2011; 9: 2056-2060.
27. Viera C, Felix S, Saavedra C, Felix E, Alfaro R, Elizabeth C. Efecto diuretico de Phyllanthus niruri “Chanca piedra” Y niveles de excrecion de sodio en Rattus rattus var. albinus. UCV Scientia 2011; 3: 55-57.

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