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Published on: December 28, 2017
Prosapogenin CP4 and ursolic acid from Eriocapitella rivularis inhibit fluconazole-resistant Candida albicans
Wen-Biao Zu1, Zhao-Jie Wang1, Dong-Mei Tang1
1Yunnan Characteristic Plant Extraction Laboratory, Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan Province, School of Chemical Science and Technology, Yunnan University, Kunming 650500, PR China.
Background:
Fungal diseases affect over one billion individuals worldwide and represent a significant public health concern. Oral candidiasis (OC) is a common fungal infection primarily caused by Candida albicans. Eriocapitella rivularis is a traditional medicinal herb for the treatment of oral fungal infections.
Purpose:
This study aimed to identify potent antifungal compounds from E. rivularis and elucidate their underlying mechanisms of action.
Methods:
Bio-guided isolation combined with network pharmacology was used to identify anti-C. albicans compounds from E. rivularis, followed by metabolomics analysis to explore potential regulatory pathways. Antifungal activity and synergistic efficacy were evaluated using broth microdilution, checkerboard, and time-kill assays. Biofilm inhibition was assessed through quantitative and biochemical analyses. Reverse transcription quantitative polymerase chain reaction was performed to elucidate molecular mechanisms. An in vivo murine OC model was employed to verify efficacy.
Results:
Prosapogenin CP4 disrupted the fungal cell wall, targeted ergosterol to induce plasma membrane permeabilization, inactivated mitochondrial function, and inhibited hyphal growth, potentially through interference with ABC transporters, modulation of cAMP export, and induction of metabolic disorders. Prosapogenin CP4 and ursolic acid exhibited a synergistic inhibitory effect against fluconazole-resistant C. albicans (FICI = 0.375) with low resistance. This combination regulated genes in the Ras/cAMP/PKA signalling pathway, significantly inhibited biofilm formation and reduced fungal burden, inflammatory responses, and fungal colonisation in murine oral tissues, with efficacy comparable or superior to that of nystatin.
Conclusion:
The finding presents a synergistic phytomedicine strategy using two triterpenoids from E. rivularis as a promising therapeutic approach for OC, particularly biofilm-associated infections.
Insights
This study found that two compounds from Eriocapitella rivularis, prosapogenin CP4 and ursolic acid, show synergistic antifungal activity against Candida albicans, offering a new treatment for oral candidiasis.
Area of Science:
- Mycology
- Pharmacology
- Natural Products Chemistry
Background:
- Fungal diseases, including oral candidiasis (OC) caused by Candida albicans, affect over a billion people globally.
- Eriocapitella rivularis is a traditional herb used to treat oral fungal infections.
Purpose of the Study:
- To identify potent antifungal compounds from E. rivularis.
- To elucidate the mechanisms of action of these compounds against C. albicans.
Main Methods:
- Bio-guided isolation and network pharmacology identified anti-C. albicans compounds.
- Antifungal, synergistic, and biofilm inhibition assays were performed.
- In vivo efficacy was tested in a murine OC model.
Main Results:
- Prosapogenin CP4 disrupted the fungal cell wall and plasma membrane, inhibited mitochondrial function, and affected hyphal growth.
- Prosapogenin CP4 and ursolic acid showed synergistic activity against fluconazole-resistant C. albicans.
- The combination inhibited biofilm formation, reduced fungal burden, and inflammation in vivo.
Conclusions:
- A synergistic phytomedicine strategy using two triterpenoids from E. rivularis offers a promising therapeutic approach for OC.
- This strategy is particularly effective for biofilm-associated oral candidiasis.
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