Evidence map›Paper›PMID 39881021›Full record

ArticleAMB Express2025

Celastrol boosts fluconazole efficacy against vaginal candidiasis: in vitro and in vivo evidence.

Fatma Al-Zahraa A Yehia, Hisham A Abbas, Tarek M Ibrahim, Basem Mansour, Zuhier A Awan, Mohammed W Al-Rabia, Wesam H Abdulaal, Mustafa Adnan Zeyadi, Solomon Z Okbazghi, Tarek S Ibrahim and 2 more

Abstract read
In one paragraph

Article in AMB Express, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Fatma Al-Zahraa A YehiaDepartment of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt.ORCID http://orcid.org/0000-0003-1177-424X
Hisham A AbbasDepartment of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt.
Tarek M IbrahimDepartment of Pharmaceutics, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt.
Basem MansourDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Belqas, 11152, Egypt.
Zuhier A AwanDepartment of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
Mohammed W Al-RabiaDepartment of Medical Microbiology and Parasitology, Faculty of Medicine, King Abdulaziz University, Jeddah, 21589, Saudi Arabia.
Wesam H AbdulaalDepartment of Biochemistry, Faculty of Science, Cancer and Mutagenesis Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, 21589, Saudi Arabia.
Mustafa Adnan ZeyadiDepartment of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
Solomon Z OkbazghiGlobal Analytical and Pharmaceutical Development, Alexion Pharmaceuticals, New Haven, Connecticut, 06510, USA.
Tarek S IbrahimDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah, 21589, Saudi Arabia.
Wael A H HegazyDepartment of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt. waelmhegazy@daad-alumni.de.ORCID http://orcid.org/0000-0001-5683-4803
Salwa E GomaaDepartment of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Candida albicans is a commensal fungus that naturally inhabits the vagina. However, overgrowth of C. albicans can result in vulvovaginal candidiasis (VVC), one of the most prevalent fungal infections affecting women. The rapid emergence of azole resistance in C. albicans, in addition to the limited available antifungal agents, complicates the treatment and emphasizes the urgent need for novel therapeutic options. Efflux-mediated azole resistance is a common resistance mechanism in fluconazole (FLZ)-resistant C. albicans. Combination therapy using natural compounds is a potential approach that can restore fluconazole's antifungal activity in azole-resistant isolates via efflux pump inhibition. This study aimed to evaluate the ability of celastrol, a natural triterpene, to retrieve FLZ antifungal activity against azole-resistant C. albicans in vitro and in vivo. Celastrol did not exhibit antifungal activity against the tested clinical isolates; however, the sub-MIC of celastrol inhibited rhodamine 6G (R6G) efflux and increased R6G accumulation inside celastrol-treated C. albicans cells. Synergy was spotted between celastrol and FLZ via a checkerboard assay. Quantification of m-RNA levels of efflux-mediated azole resistance genes within azole-resistant C. albicans demonstrated CDR1 overexpression. Upon celastrol treatment, a significant decline in ABC transporters transcript levels were detected. Moreover, molecular docking demonstrated that celastrol is a potential ABC efflux transporters blocker that successfully fits into target binding pockets. A negligible hemolytic effect of celastrol against human erythrocytes was observed. In the in vivo model of VVC, the combination of FLZ and celastrol in vaginal gel revealed a drastic reduction in the fungal burden with apparently normal vaginal tissue. Celastrol promising in vitro and in vivo findings strengthen its future use for the treatment of azole-resistant C. albicans.

Indexed as

Azole-resistanceCandida albicansCelastrolEfflux pumpsVaginal candidiasis

Identifiers

PMID39881021
PMCPMC11780038

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.