Protective effects of silymarin, a milk thistle (Silybium marianum) derivative on ethanol-induced oxidative stress in liver (original) (raw)
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Hepatoprotective effect of silymarin
World Journal of Hepatology, 2014
The use of medicinal plants in treating illnesses has been reported since ancestral times. In the case of hepatic diseases, several species such as Silybum marianum , Phyllanthus niruri, and Panus giganteus (Berk.) have been shown to ameliorate hepatic lesions. Silymarin is a natural compound derived from the species Silybum marianum , which is commonly known as Milk thistle. This plant contains at least seven flavoligands and the flavonoid taxifolin. The hepatoprotective and antioxidant activity of silymarin is caused by its ability to inhibit the free radicals that are produced from the metabolism of toxic substances such as ethanol, acetaminophen, and carbon tetrachloride. The generation of free radicals is known to damage cellular membranes and cause lipoperoxidation. Silymarin enhances hepatic glutathione and may contribute to the antioxidant defense of the liver. It has also been shown that silymarin increases protein synthesis in hepatocytes by stimulating RNA polymerase I activity. A previous study on humans reported that silymarin treatment caused a slight increase in the survival of patients with cirrhotic alcoholism compared with untreated controls.
Silybin and the liver: From basic research to clinical practice INTRODUCTION
Herbal products are increasingly used, mainly in chronic liver disease. Extracts of milk thistle, Silymarin and silybin, are the most prescribed natural compounds, with different indications, but with no definitive results in terms of clinical efficacy. This review analyzes the available studies on the effects of the purified product silybin, both as a free and a conjugated molecule, on liver cells or on experimentally induced liver damage, and in patients with liver disease. We searched PUBMED
Oxidative stress, lipid peroxidation, and transaminase reactions are some of the mechanisms that can lead to liver dysfunction. A time-dependent study was designed to evaluate the ability of silymarin (SLN) and glycyrrhizin (GLN) in different dosage regimens to lessen oxidative stress in the rats with hepatic injury caused by the hepatotoxin carbon tetrachloride. Wistar male albino rats ( = 60) were randomly assigned to six groups. Group A served as a positive control while groups B, C, D, E, and F received a dose of CCl 4 (50% solution of CCl 4 in liquid paraffin, 2 mL/kg, intraperitoneally) twice a week to induce hepatic injury. Additionally, the animals received SLN and GLN in different doses for a period of six weeks. CCl 4 was found to induce hepatic injury by significantly increasing serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and thiobarbituric acid reactive substances while decreasing total protein and the activities of reduced glutathione, superoxide dismutase, and catalase. Treatment with various doses of SLN and GLN significantly reduced ALT, AST, ALP, and TBARS levels and increased GSH, SOD, and CAT levels. Our findings indicated that SLN and GLN have hepatoprotective effects against oxidative stress of the liver.
Hepatoprotective and Antioxidant Effects of Silybum marianum Plant in Rats
International Journal for Agro Veterinary and Medical Sciences, 2011
Licorice has been used in Chinese folk medicine for the treatment of various disorders. Licorice has the biological capabilities of detoxication, antioxidation, and antiinfection. In this study, we evaluated the antihepatotoxic effect of licorice aqueous extract (LE) on the carbon tetrachloride (CCl 4)-induced liver injury in a rat model. Hepatic damage, as reveled by histology and the increased activities of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) activities, and decreased levels of serum total protein (TP), albumin (Alb) and globulin (G) were induced in rats by an administration of CCl 4 at 3 mL/kg b.w. (1:1 in groundnut oil). Licorice extract significantly inhibited the elevated AST, ALP and ALT activities and the decreased TP, Alb and G levels caused by CCl 4 intoxication. It also enhanced liver super oxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR), Glutathione S-transferase (GST) activities and glutathione (GSH) level, reduced malondialdehyde (MDA) level. Licorice extract still markedly reverses the increased liver hydroxyproline and serum TNF-α levels induced by CCl 4 intoxication. The data of this study support a chemopreventive potential of licorice extract against liver oxidative injury.
Non alcoholic steatohepatitis (NASH) is a pathological condition characterized by accumulation of lipids in the liver of non alcoholic individuals and consequent oxidative stress leading to cirrhosis of liver in the long run. Silymarin is a unique flavonoid complex extract isolated from seeds of the milk thistle plant (Silybum marianum) and has strong antioxidant and radical scavenging properties. The present research aimed to evaluate the therapeutic effects of silymarin (Slym) as natural antioxidant and anti-inflammatory on liver tissue of male rats exposed to experimental model of non alcoholic steatohepatitis (NASH) induced by supplementation of high fat diet (HFD) for 3 months, Through evaluation of serum Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) and Gamma Glutamyl-Transferase (γ-GT) activities and Albumin, Total Protein, Total Bilirubin, Total Cholesterol and triglycerides concentrations. Levels of reduced glutathione (GSH) and activities of Superoxide Dismutase (SOD) and Catalase (CAT), were determined in liver tissues. Extent of oxidative stress was also assessed by hepatic lipid peroxides (MDA). HFD supplementation induced a significant increase in 1) serum ALT, AST, ALP and γ-GT activities, in addition to Total Bilirubin, Total Cholesterol and triglycerides concentrations. 2) Liver MDA concentration. On contrast, it exhibited a significant decrease in serum Albumin and Total Protein, also marked depletion in liver GSH, CAT and SOD, were observed after HFD supplementation. Silymarin treatment was able to mitigate and ameliorate hepatic NASH induced by HFD and showed pronounced curative effect against lipid peroxidation and deviated serum enzymatic variables as well as maintained glutathione status and antioxidant enzymes toward control levels. Silymarin treatment was highly effective against HFD induced NASH. The results of the present study suggest that silymarin has the potential to exert curative effects against liver NASH.
The potential of silymarin for the treatment of hepatic disorders
Silymarin has long been used as a hepatoprotective remedy. Chronic toxicity studies in rodents have confirmed that silymarin has a very low toxicity. These data support its history as a safe medication in hepatic diseases. In the last years, several studies expanded our understanding of the pharmacology of silymarin and its molecular mechanisms of action. These new insights may affect the handling of silymarin in clinical studies and daily practice. Additionally, scientific knowledge in hepatology is constantly evolving with, particularly, an increase in the field of non-alcoholic fatty liver disease which is considered today as the most frequent liver disease worldwide. In this review, we will describe scientific evidence for the effectiveness of silymarin in hepatic disorders. We will focus on silymarin's pharmacological effects in non-alcoholic fatty liver disease and on its well described effects in alcoholic liver disease and acute intoxications, e.g. with Amanita species. We will discuss the relevance of pharmacological data as a function of doses or concentrations required for a given effect and of concentrations achieved in the target tissues. Many pharmacological effects of silymarin can be attributed to effects downstream or upstream of its antioxidative and membrane-stabilizing properties. However, despite promising new experimental and clinical data further clinical studies are required including long-term observations and the application of hard clinical endpoints such as survival rates, to further support silymarin's use for the treatment of hepatic diseases.
Free Radical Biology and Medicine, 2014
The accumulation of toxic hydrophobic bile acids in hepatocytes, observed during chronic cholestasis, induces substantial modification in the redox state and in mitochondrial functions. Recent reports have suggested a significant role of impaired lipid metabolism in the progression of chronic cholestasis. In this work we report that changes observed in the expression of the lipogenic enzymes acetyl-CoA carboxylase and fatty acid synthase were associated with a decrease in the activity of citrate carrier (CIC), a protein of the inner mitochondrial membrane closely related to hepatic lipogenesis. We also verified that the impairment of citrate transport was dependent on modification of the phospholipid composition of the mitochondrial membrane and on cardiolipin oxidation. Silybin, an extract of silymarin with antioxidant and anti-inflammatory properties, prevented mitochondrial reactive oxygen species (ROS) production, cardiolipin oxidation, and CIC failure in cirrhotic livers but did not affect the expression of lipogenic enzymes. Moreover, supplementation of silybin was also associated with mitochondrial biogenesis. In conclusion, we demonstrate that chronic cholestasis induces cardiolipin oxidation that in turn impairs mitochondrial function and further promotes ROS production. The capacity of silybin to limit mitochondrial failure is part of its hepatoprotective property.
It is well established that CCl 4 induce liver injury in animals through production of free radicals and oxidative stress, and subsequent lipid peroxidation that propagates injury. The aim of the present study was to evaluate the effect of aqueous extract of silybum marianum (SB) plant relative to silymarin (SM) as standard drug on liver enzymes, cytochrome P450 (CYP450), and histological changes using H&E and atomic force microscope (AFM). The aqueous extract of SB was prepared and the determination of total phenolic compounds in aqueous extract of silybum marianum and in silymarin standard drug was done. Results showed that CCl 4 was found to induce liver injury by significant increase in alanine transaminase (ALT), aspartate amino transferase (AST), and alkaline phosphatase (ALP), malondialdehyde (MDA), and CYP450 which were confirmed using H&E and atomic force microscope (AFM) while decreasing albumin (ALB) and activates of glutathione –S-transferase (GST), glutathione reduced (GSH), superoxide dismutase (SOD), catalase (CAT), total antioxidant capacity (TAC). Whereas, treatment with aqueous extract of SB as well as SM drug significantly decrease ALT, AST, ALP and MDA and increased ALB, GST, GSH, SOD, CAT, TAC levels as well as decreasethe level of CYP450. In conclusion, aqueous extract of SB ameliorates the toxic effects of CCl 4 by its free radical-scavenging and potent antioxidant activity and can be used for the treatment of liver injury.