Silymarine extract improved plasma homocysteine, lipids and liver enzymes in hyperhomocysteinemic non-alcoholic steatohepatitis

Introduction: Silymarine extract is currently prescribed by some physicians for treatment of fatty liver disease. In the present study, the effect of administration of tablet containing silymarine extract on plasma homocysteine (Hcy), folate, vitamin B12 and liver enzymes activity in non-alcoholic steatohepatitis (NASH) was investigated. Materials and Methods: Seventy-four patients (40 female and 34 male; aged 32-44 years) who were diagnosed with NASH and hyperhomocysteinemic by liver biopsy, measurement of liver enzymes activity and plasma Hcy were recruited for this study. The patients were not consuming alcohol or taking any other medications/medicines. Plasma Hcy, folate, B12, cholesterol, triglyceride, fasting glucose, aspartate aminotransferase (AST) and alaninaminotransferase (ALT) activity of all patients were measured before and after treatment. Tablet containing silymarine extract (140mg∕kg) was administrated thrice /three times a day for 2 months. Results: The results showed a significant reduction in the level of plasma Hcy, cholesterol, triglyceride, fasting glucose (P <0.05) following the administration of tablet containing silymarine extract, however, the increase in plasma folate and B12 levels was not significant. The results did not demonstrate any significant negative correlations between Hcy and B12, and also between Hcy and folate. Conclusion: It can be concluded that consumption of tablet containing silymarine extract in NASH patients significantly reduces level of plasma Hcy, cholesterol, triglyceride, fasting glucose and AST and ALT activity, while level of plasma folate and B12 remained unchanged. D ow nl oa de d fr om w w w .p hy ph a. ir at 2 1: 13 IR S T o n T hu rs da y O ct ob er 1 3t h 20 16 140 | Physiol Pharmacol 19 (2015) 139-145 Jelodar et al. Fig.1. Homocysteine metabolism obesity, insulin resistance states including diabetes and other types of the metabolic syndroms, such as high triglycerides and low HDL. Most patients with NAFLD have few or no symptoms. Patients may complain of fatigue, malaise and dull right-upperquadrant abdominal discomfort (Mehta et al, 2002, Marchesini et al, 2003, Luyckx et al., 2000). Homocysteine (Hcy) is a non-protein forming sulfur amino acid, synthesized from methionine (Met), whose metabolism is the result of of two metabolic pathways (Fig.1): remethylation and trans-sulfuration. Plasma Hcy level is influenced by folate, vitamin B6, B12, methylene tetrahydrofolate reductase (MTHFR), cystathionine-b-synthase and s-adenosyl methionine (Refsum et al., 2004; Scott et al.,1998; Selhub et al ,1999). Folate is also an essential substrate in remethylation of homocysteine into methionine. In folate –dependent homocysteine remethylation, vitamin B12 (cobalamin) is a cofactor for methionine synthase. Vitamin B6 is a cofactor for cystathionine-bsynthase, which is necessary for the transsulfuration of homocysteine into cysteine (Selhub et al., 1999, Fowler et al, 2005; Finkelstein et al, 2007). Homocysteine was reported to be significantly higher in the non-alcoholic steatohepatitis patients when compared with simple steatosis group, and Plasma homocysteine is a parameter for distinguishing steatohepatitis from simple steatosis (Gulsen et al, 2005). Silybummarianum L. (also known as: Milk thistle and Carduus marianum), a member of asteraceae family, is an ancient medicinal plant which has been used for centuries for treatment of different diseases such as liver and gallbladder disorders, protecting liver against snake bite /venom and insect stings, mushroom poisoning and alcohol abuse (Kren et al, 2005, Girish et al, 2006). Silymarin is the active component of this herb, which is a combination of other components, mainly silybin A, silybin, B, isosilybin A, isosilybin B and also other flavonolignants such as silychristin, neosilyhermin, silyhermin and silydianin which exist in its fruit and seeds (Dermarderosin et al, 2001, Kaur et al, 2007, Basiglio et al, 2009). Moreover, silymarin has antifibrotic, immunomodulating, anti-inflammatory (Dehmlow et al, 1996, Fantozzi et al, 1986) as well as antioxidant (Fathy et al,2009, Machlin, 1987) properties. It was also recommended for treatment of hepatitis, hepatic cirrhosis and mushroom poisoning D ow nl oa de d fr om w w w .p hy ph a. ir at 2 1: 13 IR S T o n T hu rs da y O ct ob er 1 3t h 20 16 Silymarin, plasma homocysteine, lipids and liver enzymes Physiol Pharmacol 19 (2015) 139-145 | 141 (Cesanow et al, 2006, Karimi et al, 2005, WenWuet al, 2009). Silymarine extract in the form of tablet is currently prescribed in some of the clinics for treatment of fatty liver disease, while the exact mechanism of action of this drug on hepatic patients is not clear, one possibility is acting to improve Hcy level. Hence, this study was conducted to evaluate the effect of this herbal medicine on activity of liver enzymes, Hcy, vitamin B12 and plasma lipids in NASH patients. Materials and methods