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

作　　者：Xiaoyue Liang Ding Chen Jiannan Wang Binyou Liao Jiawei Shen Xingchen Ye Zheng Wang Chengguang Zhu Lichen Gou Xinxuan Zhou Lei Cheng Biao Ren Xuedong Zhou 

机构地区：[1]State Key Laboratory of Oral Diseases&National Center for Stomatology&National Clinical Research Center for Oral Diseases&West China Hospital of Stomatology,Sichuan University,Chengdu,China [2]State Key Laboratory of Oral Diseases&National Center for Stomatology&National Clinical Research Center for Oral Diseases&Department of Operative Dentistry and Endodontics,West China Hospital of Stomatology,Sichuan University,Chengdu,China

出　　处：《International Journal of Oral Science》2023年第4期613-625,共13页国际口腔科学杂志（英文版）

基　　金：the National Natural Science Foundation of China grants(81870778,82071106,82271033,81991500,81991501,82201046);Key Research and Development Projects of Science and Technology Department of Sichuan Province(2021YFQ0064);Technology Innovation R&D Project of Chengdu(2022-YF05-01401-SN);Applied Basic Research Programs of Sichuan Province(2020YJ0227).

摘　　要：Candida albicans is the most abundant fungal species in oral cavity. As a smart opportunistic pathogen, it increases the virulence byswitching its forms from yeasts to hyphae and becomes the major pathogenic agent for oral candidiasis. However, the overuse ofcurrent clinical antifungals and lack of new types of drugs highlight the challenges in the antifungal treatments because of the drugresistance 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 andarteether, were employed to target at the hyphal development, the most important virulence factor of C. albicans. Artemisininsfailed to affect the growth, but significantly inhibited the hyphal development of C. albicans, including the clinical azole resistantisolates, and reduced their damage to oral epithelial cells, while arteether showed the strongest activities. The transcriptomesuggested that arteether could affect the energy metabolism of C. albicans. Seven artemisinins were then proved to significantlyinhibit the productions of ATP and cAMP, while reduced the hyphal inhibition on RAS1 overexpression strain indicating thatartemisinins regulated the Ras1-cAMP-Efg1 pathway to inhibit the hyphal development. Importantly, arteether significantlyinhibited the fungal burden and infections with no systemic toxicity in the murine oropharyngeal candidiasis models in vivo causedby both fluconazole sensitive and resistant strains. Our results for the first time indicated that artemisinins can be potentialantifungal compounds against C. albicans infections by targeting at its hyphal development.

关 键 词：INS DRUGS inhibited 

分 类 号：R276.8[医药卫生—中医五官科学]