α-Hemolysin (Hla) is a significant virulence factor in
Staphylococcus aureus
(
S. aureus
)-caused infectious diseases such as pneumonia. Thus, to prevent the production of Hla when treating
S. aureus
infection, it is necessary to choose an antibiotic with good antibacterial activity and effect. In our study, we observed that Fosfomycin (FOM) at a sub-inhibitory concentration inhibited expression of Hla. Molecular dynamics demonstrated that FOM bound to the binding sites LYS 154 and ASP 108 of Hla, potentially inhibiting Hla. Furthermore, we verified that staphylococcal membrane-derived vesicles (SMVs) contain Hla and that FOM treatment significantly reduced the production of SMVs and Hla. Based on our pharmacological inhibition analysis, ERK and p38 activated NLRP3 inflammasomes. Moreover, FOM inhibited expression of MAPKs and NLRP3 inflammasome-related proteins in
S. aureus
as well as SMV-infected human macrophages (MΦ) and alveolar epithelial cells.
In vivo
, SMVs isolated from
S. aureus
DU1090 (an isogenic Hla deletion mutant) or the strain itself caused weaker inflammation than that of its parent strain 8325-4. FOM also significantly reduced the phosphorylation levels of ERK and P38 and expression of NLRP3 inflammasome-related proteins. In addition, FOM decreased MPO activity, pulmonary vascular permeability and edema formation in the lungs of mice with
S. aureus
-caused pneumonia. Taken together, these data indicate that FOM exerts protective effects against
S. aureus
infection
in vitro
and
in vivo
by inhibiting Hla in SMVs and blocking ERK/P38-mediated NLRP3 inflammasome activation by Hla.
Accumulating evidence has indicated that corosolic acid exerts anti-diabetic, anti-obesity, anti-inflammatory, anti-hyperlipidemic and anti-viral effects. More importantly, corosolic acid has recently attracted much attention due to its anticancer properties and innocuous effects on normal cells. Furthermore, the increasing proportion of obese and/or diabetic populations has led to an epidemic of non-alcoholic fatty liver disease (NAFLD), which frequently progresses to hepatocellular carcinoma (HCC). Evidence has indicated that NAFLD is closely associated with the development of HCC and comprises a high risk factor. The present review summarizes the anticancer effects of corosolic acid in vitro and in vivo, and its related molecular mechanisms. It also describes the inhibitory effects of corosolic acid on the progression of NAFLD and its associated molecular mechanisms, providing guidance for future research on corosolic acid in NAFLD-related HCC prevention and treatment. To the best of our knowledge, a review of corosolic acid as an anticancer agent has not yet been reported. Due to its multitargeted activity in cancer cells, corosolic acid exerts anticancer effects when administered alone, and acts synergistically when administered with chemotherapeutic drugs, even in drug-resistant cells. In addition, as a novel tool to treat metabolic syndromes, corosolic acid uses the same mechanism in its action against cancer as that used in the progression of NAFLD-related HCC. Therefore, corosolic acid has been suggested as an agent for the prevention and treatment of NAFLD-related HCC.
Objectives To investigate the neuroprotective effects of six natural compounds (caffeine, gallic acid, resveratrol, epigallocatechin gallate [EGCG], L-ascorbic acid and alpha tocopherol [Vitamin E] on heavy metal-induced cell damage in rat PC12 cells. Methods In this in vitro experiment, rat PC12 cells were exposed to four heavy metals (CdCl2, HgCl2, CoCl2 and PbCl2) at different concentrations and cell apoptosis, necrosis and oxidative stress were assessed with and without the addition of the six natural compounds. Results The metals decreased cell viability but the natural compounds attenuated their effects on apoptosis, necrosis and reactive oxygen species (ROS) levels. Mitochondrial protein changes were involved in the regulation. Conclusion Overall, the natural compounds did provide protection against the metal-induced PC12 cell damage. These data suggest that natural compounds may have therapeutic potential against metal-induced neurodegenerative disease.
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