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The filamentation of C. albicans is a hallmark of biofilm formation, accompanied by the occurrence of a hypoxic microenvironment. Paeonol (PAE) is a traditional medicine with multiple properties. In a previous study, we demonstrated the synergism of PAE plus Fluconazole (FLU) or Amphotericin B (AmB) against C. albicans in vitro and in vivo. This study aimed to explore the therapeutic mechanisms of drug combinations on OPC. In an established OPC mouse model, the culture of hypoxia was observed by calcofluor white and hypoxyprobe staining. The expression and levels of IL-17 signaling-associated genes and proteins (IL-17A and IL-23) were evaluated in tissue homogenates and EC109 cells. The results show that compared with the single therapy, PAE plus FLU or AmB can decrease fungal burden, restore mucosal integrity, and reduce the hypoxic microenvironment and inflammation in the OPC mice. Relative to infected mice, the drug combinations can also rectify the abnormal expression of hypoxia inducible factor (hif)-1\u03b1, il-17a, and il-23 mRNA. Meanwhile, compared with the infected EC109 cells treated with a single drug, PAE plus FLU or AmB significantly inhibited the mRNA and protein expression of HIF-1\u03b1, IL-17A, and IL-23. Taken together, the possible mechanism of PAE plus FLU or AmB can be attributed to the regulation of hypoxia-associated IL-17 signaling in OPC treatment.<\/jats:p>","DOI":"10.1093\/mmy\/myac011","type":"journal-article","created":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T20:14:32Z","timestamp":1643400872000},"source":"Crossref","is-referenced-by-count":10,"title":["Paeonol enhances treatment of fluconazole and amphotericin B against oropharyngeal candidiasis through HIF-1\u03b1 related IL-17 signaling"],"prefix":"10.1093","volume":"60","author":[{"given":"Min","family":"Pan","sequence":"first","affiliation":[{"name":"Laboratory of Infection and Immunity, College of Integrated Chinese and Western Medicine (College of Life Science), Anhui University of Chinese Medicine, Zhijing Building, 350 Longzihu Road, Xinzhan District, Hefei 230012, Anhui, P. R. 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China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daqiang","family":"Wu","sequence":"additional","affiliation":[{"name":"Laboratory of Infection and Immunity, College of Integrated Chinese and Western Medicine (College of Life Science), Anhui University of Chinese Medicine, Zhijing Building, 350 Longzihu Road, Xinzhan District, Hefei 230012, Anhui, P. R. China"},{"name":"Institute of Integrated Traditional Chinese and Western Medicine, Anhui Academy of Chinese Medicine, Zhijing Building, 350 Longzihu Road, Xinzhan District, Hefei 230012, Anhui, P. R. China"},{"name":"CAS Center for Excellence in Molecular Cell Sciences, Ministry of Education Key Laboratory for Membrane-less Organelles & Cellular Dynamics, Hefei National Laboratory for Physical Sciences at the Microscale, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, 230027 Hefei, P.R. 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