Silymarin as Supportive Treatment in Liver Diseases: A Narrative Review

Abstract

Silymarin, an extract from milk thistle seeds, has been used for centuries to treat hepatic conditions. Preclinical data indicate that silymarin can reduce oxidative stress and consequent cytotoxicity, thereby protecting intact liver cells or cells not yet irreversibly damaged. Eurosil 85 Ò is a proprietary formulation developed to maximize the oral bioavailability of silymarin. Most of the clinical research on silymarin has used this formulation. Silymarin acts as a free radical scavenger and modulates enzymes associated with the development of cellular damage, fibrosis and cirrhosis. These hepatoprotective effects were observed in clinical studies in patients with alcoholic or nonalcoholic fatty liver disease, including patients with cirrhosis. In a pooled analysis of trials in patients with cirrhosis, silymarin treatment was associated with a significant reduction in liverrelated deaths. Moreover, in patients with diabetes and alcoholic cirrhosis, silymarin was also able to improve glycemic parameters. Patients with drug-induced liver injuries were also successfully treated with silymarin. Silymarin is generally very well tolerated, with a low incidence of adverse events and no treatment-related serious adverse events or deaths reported in clinical trials. For maximum benefit, treatment with silymarin should be initiated as early as possible in patients with fatty liver disease and other distinct liver disease manifestations such as acute liver failure, when the regenerative potential of the liver is still high and when removal of oxidative stress, the cause of cytotoxicity, can achieve the best results.

Multidrug Resistance Modulation Activity of Silybin Derivatives and Their Anti-Inflammatory Potential

“…In recent studies, both silybin and 2,3-dehydrosilybin showed promising results not only prevention of chronic liver damage [10], but also in anti-inflammatory and antifibrotic therapies [1 In hepatic stellate cells (HSC), silybin decreased cell proliferation induced by platelet-derived grow factor (PDGF) and blocked de novo synthesis of collagen type I by reducing transforming grow factor-β1 (TGF-β) [12]. Furthermore, silybin and its congener silychristin inhibited IL-1β-induc formation of blood platelet-leukocyte aggregates in whole blood samples.…”

“…Nowadays, proposed cancer treatment regimens involve a new approach using natural compounds with limited or no cytotoxic effects on healthy cells, exploiting synergistic or adjuvant effects. Silybin is a typical example of such compound as it effectively inhibited overexpression of epidermal growth factor receptor (EGFR) and could be a potential target for therapeutic efficacy In recent studies, both silybin and 2,3-dehydrosilybin showed promising results not only in prevention of chronic liver damage [10], but also in anti-inflammatory and antifibrotic therapies [11]. In hepatic stellate cells (HSC), silybin decreased cell proliferation induced by platelet-derived growth factor (PDGF) and blocked de novo synthesis of collagen type I by reducing transforming growth factor-β1 (TGF-β) [12].…”

“…Despite their min were shown to have more than one order of magnitude effects than their parent flavonolignans. The presence o confers considerably higher antioxidant potency, resultin 10-fold better inhibition of lipid peroxidation compare dehydrosilybin, especially cyto-and neuro-protection, hav In recent studies, both silybin and 2,3-dehydrosilyb prevention of chronic liver damage [10], but also in anti-in In hepatic stellate cells (HSC), silybin decreased cell prolife factor (PDGF) and blocked de novo synthesis of collagen factor-β1 (TGF-β) [12]. Furthermore, silybin and its cong formation of blood platelet-leukocyte aggregates in whole the release of pro-inflammatory cytokines IL-2, TNF-α, an ƴ in a dose-dependent manner [11].…”

Suaeda vermiculata Aqueous-Ethanolic Extract-Based Mitigation of CCl4-Induced Hepatotoxicity in Rats, and HepG-2 and HepG-2/ADR Cell-Lines-Based Cytotoxicity Evaluations

“…The internally produced glutathione and other enzymatic entities counteract the liver injury caused by the ROS, the reactive nitrogen-based species, and the produced oxidative stress. The oral supplementation of antioxidants for liver disorders has been studied, and several non-enzymatic antioxidants, (e.g., ascorbic acid, α-tocopherol, silibinin, naringenin, quercetin, curcumin, resveratrol, products of phenolic, flavonoid, tannin, and carotenoid types) have been exploited [ 21 , 22 , 23 ], and the plant-origin secondary metabolite-based antioxidants have revealed promising in vivo therapeutic effects on liver disorders in studied animal models [ 24 ], though clinical studies were deemed inconclusive [ 23 ]. However, the protective roles of these antioxidants on the liver, in experimentally induced-liver injury and toxication, have been investigated for various pure, single component natural products, and on the naturally-sourced plants’ extracts, as well as mixtures of synergistic natural products containing antioxidants of a structurally-varied chemical nature, and were found to be effective [ 9 , 25 , 26 , 27 , 28 ].…”

Nonalcoholic fatty liver disease and atrial fibrillation: possible pathophysiological links and therapeutic interventions

“…Silymarin is a flavonoid extract from milk thistle seeds that exhibits antioxidant and anti-inflammatory properties [ 72 ]. Silymarin has shown beneficial anthropometric, biochemical, and histologic effects in NAFLD patients [ 73 ]. In a trial involving 102 patients undergoing cardiac surgery, silymarin was shown to decrease postoperative proinflammatory cytokines (IL-6 and TNF-α) [ 74 ].…”