Isochlorogenic Acid C

Isochlorogenic acid C (ICAC) has been used for the production of scented tea, medicinal tea, and soft drinks. The antiinflammatory, antibacterial, and antiviral properties of ICAC were demonstrated previously. However, it is unknown how ICAC regulates oxidative stress. In the current study, we evaluate the antioxidative potential of ICAC and its effects on the activation of the antioxidant system in mouse embryonic fibroblast NIH/3T3 cells. Our results showed that ICAC protected cells from H₂O₂-induced toxicity through protecting cell viability and cytotoxicity. H₂O₂-increased cellular reactive oxygen species (ROS), mitochondrial membrance potential (MMP) loss, and mitochondrial calcium were recovered by ICAC treatment. Moreover, cleaved caspase 3, SOD2, and SIRT3 were also regulated by ICAC treatment. Mechanistically, it was found that MAPK pathway is the key regulator in the insight of ICAC treatment. All intracellular changes were abrogated by the application of SIRT inhibitors, JNK inhibitor, and Erk inhibitor, but not by p38 inhibitor. Interestingly, the application of NAC revealed that the behavior of ICAC was similar to NAC regarding antioxidant potential. Conclusively, ICAC was found to be a good candidate for protecting fibroblast cells from apoptosis via reducing oxidative stress and activation of the antioxidant system. Our findings are the first to evaluate the antioxidative characteristics of ICAC and provide the novel insights when assessing the therapeutic roles of antioxidants in future cancer treatment.

Bagaza virus (BAGV) is a mosquito-borne flavivirus and has caused significant avian death in many regions, and also garnered recognition as a significant human pathogen causing diseases like encephalitis. The genome of BAGV encodes ten proteins including three structural proteins and seven nonstructural proteins. The C-terminus of the BAGV NS3 helicase serves as a helicase during BAGV replication, aiding in ATP hydrolysis and unwinding of double-stranded RNA. Here we determined the crystal structure of BAGV helicase and revealed the NTP and RNA binding pockets in the helicase which may be used for exploiting antiviral therapeutics. Using structure-based virtual screening, we discovered 20 compounds targeting both NTP and RNA binding pockets of the helicase. Molecular docking, mutation analysis, isothermal calorimetry (ITC) and the ATPase activity assay demonstrated that epigallocatechin-3-gallate (EGCG), and other top three screened compounds (Quercitrin, Citicoline sodium, Isochlorogenic acid C), showed binding affinities for both the NTP binding site and the RNA binding site of BAGV helicase, and inhibited the ATPase activity of the helicase. Taken together, our discovery of dual-target inhibitors provides a viable strategy for advancing innovative therapies against BAGV, as well as other flaviviruses.