Liver fibrosis, defined as persistent activation of hepatic stellate cells (HSCs) and the excessive accumulation of extracellular matrix (ECM) in the liver, belongs to one of the most prevalent chronic liver diseases. Advanced liver fibrosis often developed into liver cirrhosis and even liver cancer that confer a higher fatality rate. Given that liver fibrosis is potentially reversible, it is of great significance to explore the novel antifibrotic therapies and deeper mechanisms. However, there is as yet no Food and Drug Administration (FDA)-approved therapy. Considering the severe situation and the side effects that limited the development of liver fibrosis, searching for novel mechanisms or treatments remains an under-explored area in regard to improving the condition of this disease.
There have been extensive studies on the exploration of the underlying mechanisms and novel drug discovery on liver fibrosis. It is known that liver fibrosis is characterized by over-accumulation of ECM and the pathogenesis involves hepatocyte cell death and apoptosis, HSC activation, production of myofibroblast cells, activation of macrophages, and infiltration of leukocytes. Meanwhile, the other underlying mechanisms such as myofibroblast activation and the influence by other organs like the intestine have been widely reported in recent years. Strategies concentrated on the regression of the disease mainly can be summarized as removing the cause of liver injury (antiviral drugs), inhibiting hepatocyte apoptosis (PPARd agonists), inhibiting hepatic inflammation (caspase inhibitors), blocking HSC activation (Hedgehog inhibitors), and modulation of ECM deposition (LOX inhibitor), which closely focuses on the revealed mechanisms of liver fibrosis. Multiple studies have reported that the combination of small molecules targeting different pathways has been successfully used in the treatment of liver fibrosis in animal models, indicating that combined pharmacotherapy may be a promising strategy for the treatment of liver fibrosis. Despite many anti-fibrotic therapeutic agents that have exhibited effects both in vitro and in vivo experiments, most of them have severe side effects that hinder their further development. Therefore, we expect more papers focusing on the discovery of novel therapeutic agents on liver fibrosis as well as the advanced mechanisms.
This Research Topic encourages scientists to share their work on drug discovery to treat liver fibrosis or the current advances of novel mechanisms on the disease, encompassing original research, review articles, and clinical studies. The outstanding work of bioactivity-guided drug screening is useful for novel active compounds discovery, the combination pharmacotherapy targeting vital but different pathways derived from Chinese herbs provides new strategy for drug discovery, and the application of advanced technologies including multiple omics techniques promotes the discovery of novel targets. This topic includes the following aspects but is not limited to:
• The novel molecular targets and pathways of liver fibrosis
• The novel mechanisms concerning the crosstalk between different organs that promote liver fibrosis
• Active compounds from both chemical synthesis and natural plants for treating liver fibrosis and explore the corresponding mechanism of these compounds.
• Pre-clinical or clinical updates on the use of conventional drugs or natural products.
In addition, for manuscripts dealing with plant extracts or other natural substances/compounds, the composition and the stability of the study material must be described in sufficient detail. In particular, for extracts, chromatograms with the characterization of the dominating compound(s) are requested. The level of purity must be proven and included.
Liver fibrosis, defined as persistent activation of hepatic stellate cells (HSCs) and the excessive accumulation of extracellular matrix (ECM) in the liver, belongs to one of the most prevalent chronic liver diseases. Advanced liver fibrosis often developed into liver cirrhosis and even liver cancer that confer a higher fatality rate. Given that liver fibrosis is potentially reversible, it is of great significance to explore the novel antifibrotic therapies and deeper mechanisms. However, there is as yet no Food and Drug Administration (FDA)-approved therapy. Considering the severe situation and the side effects that limited the development of liver fibrosis, searching for novel mechanisms or treatments remains an under-explored area in regard to improving the condition of this disease.
There have been extensive studies on the exploration of the underlying mechanisms and novel drug discovery on liver fibrosis. It is known that liver fibrosis is characterized by over-accumulation of ECM and the pathogenesis involves hepatocyte cell death and apoptosis, HSC activation, production of myofibroblast cells, activation of macrophages, and infiltration of leukocytes. Meanwhile, the other underlying mechanisms such as myofibroblast activation and the influence by other organs like the intestine have been widely reported in recent years. Strategies concentrated on the regression of the disease mainly can be summarized as removing the cause of liver injury (antiviral drugs), inhibiting hepatocyte apoptosis (PPARd agonists), inhibiting hepatic inflammation (caspase inhibitors), blocking HSC activation (Hedgehog inhibitors), and modulation of ECM deposition (LOX inhibitor), which closely focuses on the revealed mechanisms of liver fibrosis. Multiple studies have reported that the combination of small molecules targeting different pathways has been successfully used in the treatment of liver fibrosis in animal models, indicating that combined pharmacotherapy may be a promising strategy for the treatment of liver fibrosis. Despite many anti-fibrotic therapeutic agents that have exhibited effects both in vitro and in vivo experiments, most of them have severe side effects that hinder their further development. Therefore, we expect more papers focusing on the discovery of novel therapeutic agents on liver fibrosis as well as the advanced mechanisms.
This Research Topic encourages scientists to share their work on drug discovery to treat liver fibrosis or the current advances of novel mechanisms on the disease, encompassing original research, review articles, and clinical studies. The outstanding work of bioactivity-guided drug screening is useful for novel active compounds discovery, the combination pharmacotherapy targeting vital but different pathways derived from Chinese herbs provides new strategy for drug discovery, and the application of advanced technologies including multiple omics techniques promotes the discovery of novel targets. This topic includes the following aspects but is not limited to:
• The novel molecular targets and pathways of liver fibrosis
• The novel mechanisms concerning the crosstalk between different organs that promote liver fibrosis
• Active compounds from both chemical synthesis and natural plants for treating liver fibrosis and explore the corresponding mechanism of these compounds.
• Pre-clinical or clinical updates on the use of conventional drugs or natural products.
In addition, for manuscripts dealing with plant extracts or other natural substances/compounds, the composition and the stability of the study material must be described in sufficient detail. In particular, for extracts, chromatograms with the characterization of the dominating compound(s) are requested. The level of purity must be proven and included.