Sanguinarine, Isolated From Macleaya cordata, Exhibits Potent Antifungal Efficacy Against Candida albicans Through Inhibiting Ergosterol Synthesis
In recent decades, infections caused by the opportunistic fungus Candida albicans have increased, especially in patients with immunodeficiency. In this study, we investigated the mechanism of action of sanguinarine (SAN) against C. albicans both in vitro and in vivo. SAN exhibited antifungal activit...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-06-01
|
| Series: | Frontiers in Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2022.908461/full |
| _version_ | 1817967959067328512 |
|---|---|
| author | Ziwei Hu Hao Hu Zhili Hu Xiaojun Zhong Yifu Guan Yunshi Zhao Lu Wang Liang Ye Liliang Ming Muhammad Shahid Riaz Rajoka Zhendan He Yan Wang Xun Song Xun Song |
| author_facet | Ziwei Hu Hao Hu Zhili Hu Xiaojun Zhong Yifu Guan Yunshi Zhao Lu Wang Liang Ye Liliang Ming Muhammad Shahid Riaz Rajoka Zhendan He Yan Wang Xun Song Xun Song |
| author_sort | Ziwei Hu |
| collection | DOAJ |
| description | In recent decades, infections caused by the opportunistic fungus Candida albicans have increased, especially in patients with immunodeficiency. In this study, we investigated the mechanism of action of sanguinarine (SAN) against C. albicans both in vitro and in vivo. SAN exhibited antifungal activity against C. albicans clinical isolates, with MICs in the range of 112.8–150.5 μM. Furthermore, scanning electron and transmission electron microscopy showed that SAN induced morphological changes as well as structure disruption in C. albicans cells, including masses of cellular debris, ruptured cell walls, and membrane deformation. Flow cytometry revealed that SAN could lead to cell membrane damage, and ergosterol content analysis indicated that SAN could cause ergosterol content reduction exceeding 90%. Further, we validated the efficacy of SAN against candidiasis caused by C. albicans in a murine model, and SAN significantly improved survival and reduced weight loss compared to vehicle. The treatment of 1.5 and 2.5 mg/kg/d SAN obviously reduced the fungal burden in the kidney. In addition, histopathological examination indicated that no fungal cells were observed in lung and kidney tissues after SAN treatment. Hence, this study suggests that SAN is a promising plant-derived compound for the development of an effective anticandidal agent. |
| first_indexed | 2024-04-13T20:02:45Z |
| format | Article |
| id | doaj.art-190cd5e3daea45a288a63c83b4d36302 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-04-13T20:02:45Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-190cd5e3daea45a288a63c83b4d363022022-12-22T02:32:09ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2022-06-011310.3389/fmicb.2022.908461908461Sanguinarine, Isolated From Macleaya cordata, Exhibits Potent Antifungal Efficacy Against Candida albicans Through Inhibiting Ergosterol SynthesisZiwei Hu0Hao Hu1Zhili Hu2Xiaojun Zhong3Yifu Guan4Yunshi Zhao5Lu Wang6Liang Ye7Liliang Ming8Muhammad Shahid Riaz Rajoka9Zhendan He10Yan Wang11Xun Song12Xun Song13School of Basic Medicine, School of Pharmaceutical Sciences, Respiratory Medicine Department, Shenzhen University General Hospital, Health Science Center, Shenzhen University, Shenzhen, ChinaSchool of Basic Medicine, School of Pharmaceutical Sciences, Respiratory Medicine Department, Shenzhen University General Hospital, Health Science Center, Shenzhen University, Shenzhen, ChinaHuazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, ChinaHuazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, ChinaKey Laboratory of Chemistry and Engineering of Forest Products (State Ethnic Affairs Commission), Guangxi Collaborative Innovation Center for Chemistry and Engineering of Forest Products, School of Chemistry and Chemical Engineering, Guangxi Minzu University, Nanning, ChinaSchool of Basic Medicine, School of Pharmaceutical Sciences, Respiratory Medicine Department, Shenzhen University General Hospital, Health Science Center, Shenzhen University, Shenzhen, ChinaSchool of Basic Medicine, School of Pharmaceutical Sciences, Respiratory Medicine Department, Shenzhen University General Hospital, Health Science Center, Shenzhen University, Shenzhen, ChinaSchool of Basic Medicine, School of Pharmaceutical Sciences, Respiratory Medicine Department, Shenzhen University General Hospital, Health Science Center, Shenzhen University, Shenzhen, ChinaPeople's Hospital of Wanning, Wanning, ChinaSchool of Basic Medicine, School of Pharmaceutical Sciences, Respiratory Medicine Department, Shenzhen University General Hospital, Health Science Center, Shenzhen University, Shenzhen, ChinaCollege of Pharmacy, Shenzhen Technology University, Shenzhen, ChinaTranslational Medicine R&D Center, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, ChinaSchool of Basic Medicine, School of Pharmaceutical Sciences, Respiratory Medicine Department, Shenzhen University General Hospital, Health Science Center, Shenzhen University, Shenzhen, ChinaCollege of Pharmacy, Shenzhen Technology University, Shenzhen, ChinaIn recent decades, infections caused by the opportunistic fungus Candida albicans have increased, especially in patients with immunodeficiency. In this study, we investigated the mechanism of action of sanguinarine (SAN) against C. albicans both in vitro and in vivo. SAN exhibited antifungal activity against C. albicans clinical isolates, with MICs in the range of 112.8–150.5 μM. Furthermore, scanning electron and transmission electron microscopy showed that SAN induced morphological changes as well as structure disruption in C. albicans cells, including masses of cellular debris, ruptured cell walls, and membrane deformation. Flow cytometry revealed that SAN could lead to cell membrane damage, and ergosterol content analysis indicated that SAN could cause ergosterol content reduction exceeding 90%. Further, we validated the efficacy of SAN against candidiasis caused by C. albicans in a murine model, and SAN significantly improved survival and reduced weight loss compared to vehicle. The treatment of 1.5 and 2.5 mg/kg/d SAN obviously reduced the fungal burden in the kidney. In addition, histopathological examination indicated that no fungal cells were observed in lung and kidney tissues after SAN treatment. Hence, this study suggests that SAN is a promising plant-derived compound for the development of an effective anticandidal agent.https://www.frontiersin.org/articles/10.3389/fmicb.2022.908461/fullsanguinarineantifungalC. albicansergosterolmechanism |
| spellingShingle | Ziwei Hu Hao Hu Zhili Hu Xiaojun Zhong Yifu Guan Yunshi Zhao Lu Wang Liang Ye Liliang Ming Muhammad Shahid Riaz Rajoka Zhendan He Yan Wang Xun Song Xun Song Sanguinarine, Isolated From Macleaya cordata, Exhibits Potent Antifungal Efficacy Against Candida albicans Through Inhibiting Ergosterol Synthesis Frontiers in Microbiology sanguinarine antifungal C. albicans ergosterol mechanism |
| title | Sanguinarine, Isolated From Macleaya cordata, Exhibits Potent Antifungal Efficacy Against Candida albicans Through Inhibiting Ergosterol Synthesis |
| title_full | Sanguinarine, Isolated From Macleaya cordata, Exhibits Potent Antifungal Efficacy Against Candida albicans Through Inhibiting Ergosterol Synthesis |
| title_fullStr | Sanguinarine, Isolated From Macleaya cordata, Exhibits Potent Antifungal Efficacy Against Candida albicans Through Inhibiting Ergosterol Synthesis |
| title_full_unstemmed | Sanguinarine, Isolated From Macleaya cordata, Exhibits Potent Antifungal Efficacy Against Candida albicans Through Inhibiting Ergosterol Synthesis |
| title_short | Sanguinarine, Isolated From Macleaya cordata, Exhibits Potent Antifungal Efficacy Against Candida albicans Through Inhibiting Ergosterol Synthesis |
| title_sort | sanguinarine isolated from macleaya cordata exhibits potent antifungal efficacy against candida albicans through inhibiting ergosterol synthesis |
| topic | sanguinarine antifungal C. albicans ergosterol mechanism |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2022.908461/full |
| work_keys_str_mv | AT ziweihu sanguinarineisolatedfrommacleayacordataexhibitspotentantifungalefficacyagainstcandidaalbicansthroughinhibitingergosterolsynthesis AT haohu sanguinarineisolatedfrommacleayacordataexhibitspotentantifungalefficacyagainstcandidaalbicansthroughinhibitingergosterolsynthesis AT zhilihu sanguinarineisolatedfrommacleayacordataexhibitspotentantifungalefficacyagainstcandidaalbicansthroughinhibitingergosterolsynthesis AT xiaojunzhong sanguinarineisolatedfrommacleayacordataexhibitspotentantifungalefficacyagainstcandidaalbicansthroughinhibitingergosterolsynthesis AT yifuguan sanguinarineisolatedfrommacleayacordataexhibitspotentantifungalefficacyagainstcandidaalbicansthroughinhibitingergosterolsynthesis AT yunshizhao sanguinarineisolatedfrommacleayacordataexhibitspotentantifungalefficacyagainstcandidaalbicansthroughinhibitingergosterolsynthesis AT luwang sanguinarineisolatedfrommacleayacordataexhibitspotentantifungalefficacyagainstcandidaalbicansthroughinhibitingergosterolsynthesis AT liangye sanguinarineisolatedfrommacleayacordataexhibitspotentantifungalefficacyagainstcandidaalbicansthroughinhibitingergosterolsynthesis AT liliangming sanguinarineisolatedfrommacleayacordataexhibitspotentantifungalefficacyagainstcandidaalbicansthroughinhibitingergosterolsynthesis AT muhammadshahidriazrajoka sanguinarineisolatedfrommacleayacordataexhibitspotentantifungalefficacyagainstcandidaalbicansthroughinhibitingergosterolsynthesis AT zhendanhe sanguinarineisolatedfrommacleayacordataexhibitspotentantifungalefficacyagainstcandidaalbicansthroughinhibitingergosterolsynthesis AT yanwang sanguinarineisolatedfrommacleayacordataexhibitspotentantifungalefficacyagainstcandidaalbicansthroughinhibitingergosterolsynthesis AT xunsong sanguinarineisolatedfrommacleayacordataexhibitspotentantifungalefficacyagainstcandidaalbicansthroughinhibitingergosterolsynthesis AT xunsong sanguinarineisolatedfrommacleayacordataexhibitspotentantifungalefficacyagainstcandidaalbicansthroughinhibitingergosterolsynthesis |