The role of PI3k/AKT signaling pathway in attenuating liver fibrosis: a comprehensive review.

Excessive accumulation of extracellular matrix (ECM) components within the liver leads to a pathological condition known as liver fibrosis. Alcohol abuse, non-alcoholic fatty liver disease (NAFLD), autoimmune issues, and viral hepatitis cause chronic liver injury. Exploring potential therapeutic targets and understanding the molecular mechanisms involved in liver fibrosis are essential for the development of effective interventions. The goal of this comprehensive review is to explain how the PI3K/AKT signaling pathway contributes to the reduction of liver fibrosis. The potential of this pathway as a therapeutic target is investigated through a summary of results from in vivo and in vitro studies. Studies focusing on PI3K/AKT activation have shown a significant decrease in fibrosis markers and a significant improvement in liver function. The review emphasizes how this pathway may prevent ECM synthesis and hepatic stellate cell (HSC) activation, ultimately reducing the fibrotic response. The specific mechanisms and downstream effectors of the PI3K/AKT pathway in liver fibrosis constitute a rapidly developing field of study. In conclusion, the PI3K/AKT signaling pathway plays a significant role in attenuating liver fibrosis. Its complex role in regulating HSC activation and ECM production, demonstrated both in vitro and in vivo, underscores its potential as a effective therapeutic approach for managing liver fibrosis and slowing disease progression. A comprehensive review of this field provides valuable insights into its future developments and implications for clinical applications.

Structural changes and expression of hepatic fibrosis-related proteins in coculture of Echinococcus multilocularis protoscoleces and human hepatic stellate cells.

BACKGROUND: Echinococcus multilocularis is the causative agent of human hepatic alveolar echinococcosis (AE). AE can cause damage to several organs, primarily the liver, and have severe outcomes, such as hepatic failure and encephalopathy. The main purpose of this study was to explore the interactions between hepatic stellate cells (HSCs) and E. multilocularis protoscoleces (PSCs). The results of this study provide an experimental basis for further examination of the pathogenesis of hepatic fibrosis due to AE infection. METHODS: We investigated the role of Echinococcus multilocularis (Echinococcus genus) PSCs in hepatic fibrosis by examining structural changes and measuring hepatic fibrosis-related protein levels in cocultures of PSCs and human HSCs. Structural changes were detected by transmission electron microscopy (TEM), and levels of the hepatic fibrosis-related proteins collagen I (Col-I), alpha-smooth muscle actin (α-SMA) and osteopontin (OPN) were measured by western blotting and enzyme-linked immunosorbent assay (ELISA). RESULTS: Under coculture (1) both PSCs and HSCs exhibited morphological changes, as observed by TEM; (2) Col-I, α-SMA, and OPN expression levels, which were determined by western blotting and ELISA, significantly increased after 3 days of incubation. CONCLUSIONS: The results of this study provide insights into the molecular mechanisms of AE-induced hepatic fibrosis.

Diacerein: Recent insight into pharmacological activities and molecular pathways.

Diacerein is a symptomatic slow-acting drug in osteoarthritis (SYSADOA) and the active metabolite is rhein. It is a non-steroidal anti-inflammatory drug with unique pharmacological properties as anti-oxidant and anti-apoptosis. Diacerein has recently shown to have a potential role by mediating anti-inflammatory as well as anti-oxidant and anti-apoptosis in kidney injury, diabetes mullites, and a beneficial effect on pain relief. It may have a therapeutic role in cancer, ulcerative colitis, testicular injury and cervical hyperkeratosis. Furthermore, diacerein has a valuable addition in combination therapy as a synergetic agent. This review, the first of its kind, highlights the proposed roles of diacerein in osteoarthritis and discusses recent results supporting its emerging roles with a particular focus on how these new insights may facilitate the rational development of diacerein for targeted therapies in the future.