[Action mechanisms of Xiaoluowan (II) in the treatment of epididymitis: A network pharmacology-based study].

OBJECTIVE: To explore the potential action mechanisms of Xiaoluowan (II) (XLW-II) in the treatment of epididymitis through a network pharmacology approach. METHODS: We searched various databases for relevant targets associated with epididymitis and XLW-II and obtained the common targets of epididymitis and XLW-II on the Venny platform. We acquired the protein-protein interactions (PPI) using the STRING data and had them visualized with the Cytoscape software. After topological analysis, we retrieved the key targets, followed by gene ontology (GO) and KEGG pathway enrichment analyses using the DAVID database. RESULTS: A total of 2 38 drug targets, 2 150 disease targets and 85 common targets were identified. The core targets for the treatment of epididymitis with XLW-II identified by PPI network analysis included TNF, IL6, IL1B, MMP9, AKT1, PTGS2 and TP53. GO function analysis revealed the involvement of the common targets in such biological processes as response to hypoxia, regulation of apoptotic processes, inflammatory response, and positive regulation of the MAPK cascade. KEGG pathway analysis suggested that the signaling pathways such as the cancer pathway, PI3K-Akt pathway, protein glycosylation pathway in cancer, Ras pathway and chemokine pathway might be related to the action mechanisms of XLW-II in the treatment of epididymitis. CONCLUSION: The potential targets and signaling pathways of Xiaoluowan (II) in the treatment of epididymitis were identified on the basis of network pharmacology, which has provided a novel insight into its action mechanisms and offered a new direction for further relevant studies.

Isoliquiritigenin alleviates liver fibrosis through caveolin-1-mediated hepatic stellate cells ferroptosis in zebrafish and mice.

BACKGROUND: Liver fibrosis is a major disease that threatens people's health around the world. However, there is a lack of effective treatment to completely reverse liver fibrosis. Liver transplantation is currently the only curative option for patients with advanced cirrhosis. Ferroptosis is a newly discovered type of cell death and plays an important role in the process of liver fibrosis, but the specific mechanism needs to be clarified. HYPOTHESIS/PURPOSE: To explore the regulatory mechanism of isoliquiritigenin (ISL) in the process of liver fibrosis and the relationship between Cav-1 and ferroptosis. METHODS: In this research, zebrafish, HSC-T6 cells, and mice were used as the research object. Different ROS probes to visually detect the content and distribution of ROS in live zebrafish and cells. Lentivirus and siRNA-mediated transfection techniques were used for the construction of Cav-1 overexpression and knockdown cell lines to verify the important role of Cav-1 in vitro. RESULTS: Generally, we first elucidated that ISL relieved liver fibrosis by inducing hepatic stellate cells (HSCs) ferroptosis through repressing GPX4 expression and increasing the expression of TFR and DMT1, thus producing a large number of ROS, we also found that Cav-1 exerted its anti-hepatic fibrosis effect by promoting HSCs ferroptosis. CONCLUSION: Our results have shown that Cav-1-mediated HSCs ferroptosis is necessary for ISL to play an anti-fibrotic effect in vitro and in vivo.

Ginsenoside-Rg1 acts as an IDO1 inhibitor, protects against liver fibrosis via alleviating IDO1-mediated the inhibition of DCs maturation.

BACKGROUND: Indoleamine 2,3-dioxygenase 1 (IDO1) has been reported as a hallmark of hepatic fibrosis. Ginseng Rg1(G-Rg1) is a characterized bioactive component isolated from a traditional Chinese medicinal herb Panax ginseng C. A. Meyer (Ginseng) that used in China widely. However, the anti-hepatic fibrosis property of G-Rg1 and the underlying mechanisms of action are poorly reported. PURPOSE: Here, we researched the effect of G-Rg1 on experimental liver fibrosis in vivo and in vitro. STUDY DESIGN AND METHODS: We applied a CCL4-induced liver fibrosis in mice (wild-type and those overexpressing IDO1 by in vivo AAV9 vector) and HSC-T6 cells to detect the anti-hepatic fibrosis effect of G-Rg1 in vivo and in vitro. RESULTS: We found that G-Rg1 reduced serum levels of AST and ALT markedly. Histologic examination indicated that G-Rg1 dramatically improved the extent of liver fibrosis and suppressed the hepatic levels of fibrotic marker α-SMA in vivo and in vitro. The proliferation of HSC-T6 was significantly inhibited by G-Rg1 in vitro. Both TUNEL staining and flow cytometry demonstrated that G-Rg1 attenuated the levels of hepatocyte apoptosis in fibrotic mice. Additionally, G-Rg1 up-regulated the maturation of hepatic DCs via reducing the expression level of hepatic IDO1, which played an inverse role in the maturation of DCs. Furthermore, oral administration of G-Rg1 ameliorated IDO1 overexpression-induced worsen liver fibrosis as well as IDO1 overexpression-mediated more apparent inhibition of maturation of DCs. CONCLUSION: These results suggest that G-Rg1, which exerts its antifibrotic properties via alleviating IDO1-mediated the inhibition of DCs maturation, may be a potential therapeutic drug in treating liver fibrosis.