Clinical studies with silymarin: Fibrosis progression is the end point

Heo

Biological & Pharmaceutical Bulletin

et al. 2016

Diethylnitrosamine (DEN) is a potent toxic material that can cause necrosis and subsequent fibrosis in the liver. Based on the previously reported hepatoprotective effect of Limonium tetragonum against the proliferation of hepatic stellate cells, we tested the EtOAc soluble fraction of L. tetragonum extract (EALT) in a DEN-induced hepatotoxic rat model. The development of hepatotoxicity including mononuclear cell infiltration and fibrosis induced by intraperitoneal injections of DEN (70 mg/2 mL/kg body weight (b.w.) per week) was observed at 4, 6 and 8 weeks after the first DEN treatment. Administration of EALT (200 mg/kg body weight, per os (p.o.)) induced significant reductions in serum alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), and triglycerides (TG) in DEN-injected rats. Increased oxidative stress in DEN-induced liver fibrosis rats was diminished by EALT treatment through a decrease in malondialdehyde (MDA) and increase in superoxide dismutase (SOD). Histologic findings that included markedly attenuated mononuclear cell infiltration and fibrosis could be observed in liver samples from the EALT-treated groups. An extract of Hovenia dulcis fruit and Sylimarin were used as positive controls. The present study provides direct experimental evidence for EALT attenuated hepatic injury and fibrosis in DEN-treated mice. The L. tetragonum EtOAc fraction might be useful in treating fibrotic liver diseases.

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Protective Effects of Ethyl Acetate Soluble Fraction of <i>Limonium tetragonum</i> on Diethylnitrosamine-Induced Liver Fibrosis in Rats

Heo

Biological & Pharmaceutical Bulletin

et al. 2016

“…Vitamin A (beta carotene) treatment also decreased the liver hydroxyproline level during CCl 4 administration and reduced liver fibrosis by inhibition of LP in animal studies (Seifert et al, 1995). Several plant derived compounds such as colchicine (Colchicum dispert), silymarin (Silybum marianum), polyenylphosphatidyl choline (soy bean), ellagic acid (cruciferous vegetables), Gingko biloba composita and recently, Sho-saiko-to (extract of seven herbs in Chinese folk medicine) have been proposed as antioxidant and antifibrotic in the treatment of chronic liver disease (Seitz and Poschl, 1995;Schuppan and Hahn, 2001;Lieber et al, 1994;Thresiamma and Kuttan, 1996;Li et al, 1995;Shimizu, 2000).…”

Section: Histopathological and Immunohistochemical Findingsmentioning

confidence: 99%

The role of Urtica dioica and Nigella sativa in the prevention of carbon tetrachloride‐induced hepatotoxicity in rats

Türkdoğan

Özbek

Yener

et al. 2003

Phytotherapy Research

The role of Nigella sativa L. (Ranunculaceae) (NS) and Urtica dioica L. was investigated (UD) in the prevention of carbon tetrachloride (CCl4) induced liver fibrosis and cirrhosis. Fifty Sprague-Dawley rats were allocated into fi ve groups (I, IIA and B, IIIA and B) and CCl4 was injected biweekly to all groups. Group I (control, CCl4 only), group IIA and B (NS fixed oil and volatile oil), group IIIA and B (UD fixed oil and UD decoction extract) rats were killed at the end of week 12 and histopathological and immunohistochemical examinations of liver tissues were performed. In the control group, coagulation necrosis and hydropic degeneration were marked in the periacinar regions (zone 3) associated with fibrosis in the periacinar regions and in the portal tracts. In groups IIA-B and IIIA-B (NS and UD), none of the serious histopathological findings were detected except for sparse coagulation necrosis in the periacinar regions. ASMA-positive perisinusoidal cells with myo fibroblastic transformation and lysosomal enzyme activity suggesting fibrogenesis were also significantly more common in the control group than in the NS and UD groups. UD and NS seem to be significantly effective in the prevention of carbon tetrachloride induced hepatotoxicity in rats.

“…In a rat in-vivo model of secondary biliary fibrosis, the antifibrotic effect of silymarin was dose-dependent [10]. This has led to speculation that an increased dose of silymarin may be necessary to show an effect on clinical disease progression in human beings with liver disease [24]; this hypothesis, however, has not been tested in clinical trials. Multiple preparations containing silymarin are currently available over-the-counter, but the dose of silymarin contained in these preparations differs widely among them.…”

Section: Discussionmentioning

confidence: 99%

Silymarin in the Treatment of Patients with Primary Sclerosing Cholangitis: An Open-Label Pilot Study

et al. 2007

No effective medical therapy is available for patients with primary sclerosing cholangitis (PSC). We evaluated the safety and estimated the efficacy of silymarin in patients with PSC in a pilot study. Thirty patients with PSC were enrolled. Silymarin, 140 mg orally three times daily, was given for 1 year. A statistically significant improvement in serum alkaline phosphatase activity (1131 +/- 216 vs. 861 +/- 139, P = 0.007), and aspartate aminotransferase (AST) levels (116 +/- 15 vs. 83 +/- 11, P = 0.01) occurred with treatment. Serum bilirubin levels were not significantly affected by the treatment, while serum albumin and the Mayo risk score remained essentially unchanged. Overall, 34% of patients had a positive response to silymarin as defined by > or =50% improvement or normal status in liver tests. The results of this pilot study warrant further evaluation of silymarin in patients with PSC in a large-scale, controlled trial.