Protective Role of Cepharanthine Against Equid Herpesvirus Type 8 Through AMPK and Nrf2/HO-1 Pathway Activation
》》Journal:Viruses-Basel.
》》相关产品: Cepharanthine (SJ-MN0366)
》》产品引用描述:
》》Abstract:
Equid herpesvirus type 8 (EqHV-8) is known to cause respiratory disease and miscarriage in horses and donkeys, which is a major problem for the equine farming industry. However, there are currently limited vaccines or drugs available to effectively treat EqHV-8 infection. Therefore, it is crucial to develop new antiviral approaches to prevent potential pandemics caused by EqHV-8. This study evaluates the antiviral and antioxidant effects of cepharanthine against EqHV-8 by employing both in vitro assays and in vivo mouse models to assess its therapeutic efficacy. To assess the effectiveness of cepharanthine against EqHV-8, we conducted experiments using NBL-6 and RK-13 cells. Additionally, we developed a mouse model to validate cepharanthine's effectiveness against EqHV-8. In our in vitro experiments, we assessed the cepharanthine's ability to inhibit infection caused by EqHV-8 in NBL-6 and RK-13 cells. Our results demonstrated that cepharanthine has a dose-dependent inhibitory effect, indicating that it possesses anti-EqHV-8 properties at the cellular level. Moreover, we investigated the mechanism through which cepharanthine exerts its protective effects. It was observed that cepharanthine effectively reduces the oxidative stress induced by EqHV-8 by activating the AMPK and Nrf2/HO-1 signaling pathways. Furthermore, when administered to EqHV-8 infected mice, cepharanthine significantly improved lung tissue pathology and reduced oxidative stress. The findings presented herein collectively highlight cepharanthine as a promising candidate for combating EqHV-8 infections.
》》部分实验数据展示:
Figure 1. The effect of cepharanthine on the replication of EqHV-8 in susceptible cell lines. (A) Chemical structure of cepharanthine. (B) The cytotoxic effects of cepharanthine were evaluated in RK-13 and NBL-6 cell lines using a CCK-8 assay. Cell viability was expressed relative to control cells (which received no treatment), designated as 100%. The results represent data from three in dependent experiments. RK-13 (C,D) and NBL-6 (E,F) cells were treated with varying concentrations of cepharanthine (0, 1.25, 2.5, and 5 µM) for 2 h before being infected with EqHV-8 SDLC66 at a multiplicity of infection (MOI) of 0.1 for 1 h at 37 °C. Cells were harvested at 24 hpi to assess EqHV-8 replication via Western blotting and TCID50 assays. Additionally, an indirect immunofluorescence assay was conducted. Images of the EqHV-8 SDLC66-infected RK-13 and NBL-6 cells treated with cepharanthine were captured at 36 hpi. EqHV-8 proteins are depicted in red, while the nucleocapsid (stained with DAPI) appears in blue (G).