Candida albicans is the most abundant fungal species in oral cavity. As a smart opportunistic pathogen, it increases the virulence by switching its forms from yeasts to hyphae and becomes the major pathogenic agent for oral candidiasis. However, the overuse of current clinical antifungals and lack of new types of drugs highlight the challenges in the antifungal treatments because of the drug resistance and side effects. Anti-virulence strategy is proved as a practical way to develop new types of anti-infective drugs. Here, seven artemisinins, including artemisinin, dihydroartemisinin, artemisinic acid, dihydroartemisinic acid, artesunate, artemether and arteether, were employed to target at the hyphal development, the most important virulence factor of C. albicans. Artemisinins failed to affect the growth, but significantly inhibited the hyphal development of C. albicans, including the clinical azole resistant isolates, and reduced their damage to oral epithelial cells, while arteether showed the strongest activities. The transcriptome suggested that arteether could affect the energy metabolism of C. albicans. Seven artemisinins were then proved to significantly inhibit the productions of ATP and cAMP, while reduced the hyphal inhibition on RAS1 overexpression strain indicating that artemisinins regulated the Ras1-cAMP-Efg1 pathway to inhibit the hyphal development. Importantly, arteether significantly inhibited the fungal burden and infections with no systemic toxicity in the murine oropharyngeal candidiasis models in vivo caused by both fluconazole sensitive and resistant strains. Our results for the first time indicated that artemisinins can be potential antifungal compounds against C. albicans infections by targeting at its hyphal development.
Animals ; Mice ; Candida albicans ; Candidiasis, Oral/drug therapy* ; Antifungal Agents/pharmacology* ; Hyphae ; Artemisinins/pharmacology*

Age-related macular degeneration (AMD) is a common cause of blindness, which is still short of effective therapies.As a complex disease affected by genetical, metabolic and nutritional factors, a key factor to promote the occurrence and development of AMD is chronic inflammation.In recent years, the etiological role of abnormal complement activation in AMD has attracted lots of attention.Genetic analysis has identified a number of complement-related genes, especially CFH, affecting the susceptibility of AMD.Moreover, in vitro and in vivo studies have found that abnormal ocular and systemic complement activations are closely related to the pathological alterations of AMD, including Bruch membrane changes, drusen formation, chronic retinal inflammation and choroidal neovascularization.The dysregulation of complement activation cascades causes the damage of retinal cells, which eventually leads to the pathological changes of AMD.Accordingly, complement system has become a target for new anti-AMD therapy development.This review summarized the pathological characteristics of AMD, complement-related risk genes for AMD, and the role of abnormal complement activation in promoting the progression of AMD, so as to find new targets for AMD treatment.