{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T07:05:06Z","timestamp":1779433506948,"version":"3.53.1"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81873970"],"award-info":[{"award-number":["81873970"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"\n Introduction<\/jats:title>\n \n The rising prevalence of antifungal resistance poses a significant threat to global health, with\n Candida glabrata<\/jats:italic>\n (\n C. glabrata<\/jats:italic>\n ) emerging as a particular concern due to its increasing incidence in clinical settings and the intrinsic low susceptibility to azoles. Salvianolic acid B (SAB), a major bioactive component extracted from\n Salvia miltiorrhiza<\/jats:italic>\n , exhibits potent antioxidant properties; however, its potential as an antifungal remains unexplored.\n <\/jats:p>\n <\/jats:sec>\n \n Objectives<\/jats:title>\n \n This study aimed to evaluate the antifungal efficacy of SAB alone and in combination with azoles against\n C. glabrata<\/jats:italic>\n , both\n in vitro<\/jats:italic>\n and\n in vivo<\/jats:italic>\n , and to elucidate the underlying mechanisms.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n The antifungal efficacy of SAB alone and in combination with fluconazole (FLC), itraconazole (ITC), and voriconazole (VRC) was assessed against\n C. glabrata<\/jats:italic>\n . Synergistic interactions were determined via checkerboard microdilution assays and time-kill studies. The cytotoxicity of SAB was evaluated using lactate dehydrogenase (LDH) release assays, while\n in vivo<\/jats:italic>\n efficacy was examined using a\n Galleria mellonella<\/jats:italic>\n (\n G. mellonella<\/jats:italic>\n ) infection model. Additionally, mechanistic insights were obtained through scanning and transmission electron microscopy (SEM\/TEM) to visualize morphological and ultrastructural alterations.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n SAB exhibited marked synergistic activity with azoles against azole-resistant\n C. glabrata<\/jats:italic>\n isolates. Importantly, SAB demonstrated negligible cytotoxicity toward mammalian cells. In the\n G. mellonella<\/jats:italic>\n infection model, combination therapy with FLC and SAB significantly improved larval survival compared to FLC alone. SEM and TEM revealed extensive membrane disruption, cytoplasmic dissolution, and subcellular damage in SAB and FLC treated cells, consistent with the observed synergistic antifungal activity.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n SAB synergistically enhances azoles activity against drug-resistant\n C. glabrata<\/jats:italic>\n both\n in vitro<\/jats:italic>\n and\n in vivo<\/jats:italic>\n , with mechanisms involving membrane disruption and ultrastructural damage. These findings position SAB as a promising natural adjuvant for combination therapy against drug-resistant\n Candida<\/jats:italic>\n infections.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1838295","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T06:09:43Z","timestamp":1779430183000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Salvianolic acid B synergizes with azoles against Candida glabrata cells in vulvovaginal candidiasis"],"prefix":"10.3389","volume":"16","author":[{"given":"Yisheng","family":"Chen","sequence":"first","affiliation":[{"name":"Obstetrics & Gynecology Hospital of Fudan University, Shanghai Key Lab of Reproduction and Development, Shanghai Key Lab of Female Reproductive Endocrine Related Diseases","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuping","family":"Zhang","sequence":"additional","affiliation":[{"name":"Joint Laboratory for Biomedical Research and Pharmaceutical Innovation, The Unit of Pathogenic Fungal Infection & Host Immunity, Shanghai Institute of Materia Medica, Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loukaiyi","family":"Lu","sequence":"additional","affiliation":[{"name":"Obstetrics & Gynecology Hospital of Fudan University, Shanghai Key Lab of Reproduction and Development, Shanghai Key Lab of Female Reproductive Endocrine Related Diseases","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Obstetrics & Gynecology Hospital of Fudan University, Shanghai Key Lab of Reproduction and Development, Shanghai Key Lab of Female Reproductive Endocrine Related Diseases","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Gao","sequence":"additional","affiliation":[{"name":"Obstetrics & Gynecology Hospital of Fudan University, Shanghai Key Lab of Reproduction and Development, Shanghai Key Lab of Female Reproductive Endocrine Related Diseases","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunmei","family":"Ying","sequence":"additional","affiliation":[{"name":"Obstetrics & Gynecology Hospital of Fudan University, Shanghai Key Lab of Reproduction and Development, Shanghai Key Lab of Female Reproductive Endocrine Related Diseases","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"913","DOI":"10.18502\/ijph.v51i4.9253","article-title":"Candidadrug resistance and biofilm formation in species of vaginal origin","volume":"51","author":"Alikhani","year":"2022","journal-title":"Iran J Public Health"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3390\/jof11060406","article-title":"Phenotypic impact and multivariable assessment of antifungal susceptibility in Candida auris survival using a Galleria mellonella model","volume":"11","author":"Alvarruiz","year":"2025","journal-title":"J. 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