Preliminary Study On The Inhibitory Effect Of Dihydroartemisinin On Candida Albicans And Its Mechanism

[Background]Candida albicans is one of the most common opportunistic pathogens in humans.When the host’s immunity is significantly compromised,the environmental homeostasis is disturbed or when the host suffers from certain malignant diseases,the balance of the host’s microbial environment is disturbed and Candida albicans enters an abnormal proliferation state,resulting in skin and systemic infections.Artemisinins have been found to have a significant inhibitory effect on a variety of fungal species and induce the production of large amounts of intracellular reactive oxygen species(ROS),which accumulate in the fungus and cause oxidative damage.Ergocalciferol is an essential substance for the integrity of fungal cell membranes and cell walls.Artemisinins have been found to inhibit the activity of fungi by disrupting the integrity of their cell membranes,while reducing their invasiveness and virulence.Therefore,we investigated whether dihydroartemisinin(DHA)inhibited Candida albicans through the oxidative pathway and affected the synthesis and release of ergosterol and keratinase.In this study,we used dihydroartemisinin to interfere with Candida albicans in vitro to initially investigate its effects.[Objective]The inhibitory effects of dihydroartemisinin on C.albicans were confirmed by measuring the levels of ROS and SOD,ergocalciferol content and keratinase activity in C.albicans and exploring their effects,as well as observing the changes in their ultrastructure under electron microscopy,to provide relevant information for the application of dihydroartemisinin in the treatment of fungal infectious diseases such as C.albicans Theoretical support.[Methods](1)Candida albicans was cultured in 2 groups:Candida albicans group(control group)and Candida albicans+dihydroartemisinin group(DHA group),and the viability was tested separately to select the most suitable co-incubation concentration and co-incubation time for both.(2)The experiment was divided into two groups:Candida albicans group(control group)and Candida albicans+dihydroartemisinin group(DHA group).The levels of ROS,SOD,keratinase and ergosterol in the fungus were measured.(3)The experiment was divided into 3 groups:Candida albicans group(control group),Candida albicans+dihydroartemisinin group(DHA group).The surface changes of the fungus were observed by scanning electron microscopy and the ultrastructural changes were observed by transmission electron microscopy.[Results](1)The growth inhibition of C.albicans by DHA was concentration-dependent within a certain range,with the optimum inhibitory concentration being 300ug/ml and the optimum incubation time being 24H.(2)After DHA treatment,the content of ROS in the fungus increased,the level of SOD and keratinase activity decreased,and the content of ergosterol decreased.(3)After DHA treatment,the surface structure of the fungus was severely damaged,and the internal ultrastructure showed agglutination,vacuolation and lysis.[Conclusions](1)Inducing the production of ROS through DHA,leading to oxidative damage,inhibition of Candida albicans growth,reduction of fungal virulence and destruction of the fungal integrity structure.(2)It provides some theoretical basis for dihydroartemisinin to become a novel approach for the treatment of superficial fungal infectious diseases.