Artemisinins inhibit oral candidiasis caused by Candida albicans through the repression on its hyphal development

Abstract

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.

Artemisinic acid attenuates osteoclast formation and titanium particle-induced osteolysis via inhibition of RANKL-induced ROS accumulation and MAPK and NF-κB signaling pathways

“…According to current research on drug treatment of Ti particle-induced mouse cranium osteolysis model ( Qu et al, 2019 ; Yamada et al, 2021 ; Niu et al, 2024 ) and the administration of the artemisinin family in mice ( Wu et al, 2018 ; Liang et al, 2023 ), intraperitoneal treatment is the preferable route of administration that primarily hinges on its high bioavailability and direct delivery to the systemic circulation it provides, bypassing the gastrointestinal tract and the first-pass effect in the liver. Moreover, the precise control over dosage and timing that intraperitoneal administration offers is critical in experimental settings.…”

Fangchinoline inhibits growth and biofilm of Candida albicans by inducing ROS overproduction

“… 46 And FN also showed anti‐inflammatory activity in rat model of rheumatoid arthritis. 18 It is conceivable that in treating inflammatory diseases associated with C. albicans infections, such as C. albicans keratitis and oral candidiasis, 47 , 48 FN may function through two parallel ways: suppressing C. albicans virulence and attenuating host inflammation. However, this requires further experimental validation.…”

Quinalizarin as a potential antifungal drug for the treatment of Candida albicans fungal infection in cancer patients

“…2 ). Biofilm formation is considered a virulence factor due to its ability to confer resistance to antifungal drugs and protect fungal cells from host immune responses ( 53 , 54 ). Therefore, discovering new compounds with anti-biofilm properties seems to be crucial for the achievement of an effective therapy against C. albicans .…”