Natural Sulfur-Containing Compounds: An Alternative Therapeutic Strategy against Liver Fibrosis

Abstract

Liver fibrosis is a pathophysiologic process involving the accumulation of extracellular matrix proteins as collagen deposition. Advanced liver fibrosis can evolve in cirrhosis, portal hypertension and often requires liver transplantation. At the cellular level, hepatic fibrosis involves the activation of hepatic stellate cells and their transdifferentiation into myofibroblasts. Numerous pro-fibrogenic mediators including the transforming growth factor-β1, the platelet-derived growth factor, endothelin-1, toll-like receptor 4, and reactive oxygen species are key players in this process. Knowledge of the cellular and molecular mechanisms underlying hepatic fibrosis development need to be extended to find novel therapeutic strategies. Antifibrotic therapies aim to inhibit the accumulation of fibrogenic cells and/or prevent the deposition of extracellular matrix proteins. Natural products from terrestrial and marine sources, including sulfur-containing compounds, exhibit promising activities for the treatment of fibrotic pathology. Although many therapeutic interventions are effective in experimental models of liver fibrosis, their efficacy and safety in humans are largely unknown. This review aims to provide a reference collection on experimentally tested natural anti-fibrotic compounds, with particular attention on sulfur-containing molecules. Their chemical structure, sources, mode of action, molecular targets, and pharmacological activity in the treatment of liver disease will be discussed.

Insights into the Light Response of Skeletonema marinoi: Involvement of Ovothiol

“…Ovothiols have been receiving great interest for their biological activities in in vitro and in vivo human model systems. Indeed, they exhibited pleiotropic beneficial properties, revealing antifibrotic activities in a murine model of liver fibrosis [30,31], antiproliferative action in human cancer cell lines [32][33][34] and anti-inflammatory effects in endothelial cells derived from women affected by gestational diabetes [35]. Ovothiols are synthesized in vivo by two key enzymes, the sulfoxide synthase OvoA and the β-lyase OvoB [36,37], in three different forms, A, B and C, differing in the methylation state of the α-amino group.…”

Probing the Interactions of Sulfur-Containing Histidine Compounds with Human Gamma-Glutamyl Transpeptidase

“…We have previously identified a novel class of non-competitive-like GGT inhibitors, i.e., methyl-5-thiohistidine of marine origin (ovothiols), as an alternative therapeutic strategy for GGT-dependent diseases [16][17][18][19]41].…”

Special Issue on “Cellular and Molecular Mechanisms Underlying the Pathogenesis of Hepatic Fibrosis”

“…Milito et al provide a reference collection on experimentally tested natural sulfur-containing antifibrotic compounds [32]. Most of them are pleiotropic molecules acting as scavengers for ROS and nitric oxide, or alternatively interfering with the activity of redox-sensitive pathways involved in the progression of hepatic fibrosis.…”

“…Most of them are pleiotropic molecules acting as scavengers for ROS and nitric oxide, or alternatively interfering with the activity of redox-sensitive pathways involved in the progression of hepatic fibrosis. Although the efficacy and safety of these experimental drugs is largely unknown, their beneficial effects in experimental models make their forthcoming translation from bench to bedside realistic [2,32].…”