Abstract

Protozoa and helminths are the two main groups that cause parasitic diseases with a broad spectrum of clinical symptoms. Protozoa are unicellular organisms like the malaria parasite Plasmodium, which is responsible for the majority of deaths associated with parasitic infections. Helminths are alternative parasites that can produce debilitating diseases in hosts, some of which result in chronic infections. The discovery of effective therapeutic drugs is the key to improving health in regions of poverty and poor sanitation where these parasites usually occur. It is very encouraging that the 2015 Nobel Prize in Physiology or Medicine was awarded to Youyou Tu as well as William C. Campbell and Satoshi Õmura for their considerable contributions in discovering artemisinin and avermectin, respectively. Both drugs revolutionized therapies for filariasis and malaria, significantly reducing by large percentages their morbidity and mortality.

Abstract

The pathological increase in the levels of reactive oxygen species (ROS) in the retinal pigment epithelium (RPE), is implicated in the development of age-related macular degeneration (AMD). The discovery of drug candidates to effectively protect RPE cells from oxidative damage is required to resolve the pathological aspects and modify the process of AMD. In this study, a FDA-approved anti-malaria drug, Artemisinin was found to suppress hydrogen peroxide (H2O2)-induced cell death in human RPE cell-D407 cells. Further study showed that Artemisinin significantly suppressed H2O2− induced D407 cell death by restoring abnormal changes in nuclear morphology, intracellular ROS, mitochondrial membrane potential and apoptotic biomarkers. Western blotting analysis showed that Artemisinin was able to activate extracellular regulated ERK/CREB survival signaling. Furthermore, Artemisinin failed to suppress H2O2-induced cytotoxicity and the increase of caspase 3/7 activity in the presence of the ERK inhibitor PD98059. Taken together, these results suggest that Artemisinin is a potential protectant with the pro-survival effects against H2O2 insult through activation of the ERK/CREB pathway.