Coadministration of Ginger Extract and Fluconazole Shows a Synergistic Effect in the Treatment of Drug-Resistant Vulvovaginal Candidiasis

Arif Khan; Mohd Azam; Khaled S Allemailem; Faris Alrumaihi; Ahmad Almatroudi; Fahad A Alhumaydhi; Hafiz Iqtidar Ahmad; Masih Uzzaman Khan; Masood Alam Khan

doi:10.2147/IDR.S305503

Coadministration of Ginger Extract and Fluconazole Shows a Synergistic Effect in the Treatment of Drug-Resistant Vulvovaginal Candidiasis

Infect Drug Resist. 2021 Apr 21:14:1585-1599. doi: 10.2147/IDR.S305503. eCollection 2021.

Authors

Affiliations

¹ Department of Basic Health Sciences, College of Applied Medical Sciences, Qassim University, Buraydah, 51452, Saudi Arabia.
² Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah, 51452, Saudi Arabia.
³ Department of Tashreeh Wa Munafeul Aza, Faculty of Unani Medicine, Aligarh Muslim University, Aligarh, 202002, India.
⁴ Department of Pharmaceutical Chemistry & Pharmacognosy, Unaizah College of Pharmacy, Qassim University, Buraydah, 51452, Saudi Arabia.

^# Contributed equally.

Abstract

Background: Azoles are the most common antifungal drugs used in the treatment of vulvovaginal candidiasis (VVC). The frequency of azole-resistant Candida isolates has increased dramatically in the last two decades. Here, we assessed the antifungal activity of a combination of fluconazole (FLZ) and methanolic extract of ginger (Meth-Gin) against drug-resistant vulvovaginal candidiasis (VVC) in a murine model.

Methods: The in vitro activity of FLZ or a combination of FLZ and Meth-Gin was determined against Candida albicans by the agar well diffusion, macrodilution, time-kill and the biofilm eradication methods. The therapeutic efficacy of the formulations was assessed by analyzing the fungal load, pro-inflammatory cytokines, percent apoptotic cells and the histological changes in the vaginal tissues of the mice. Moreover, the renal toxicity the drug formulation was evaluated by analyzing the levels of the blood urea nitrogen (BUN) and creatinine.

Results: The results of in vitro study demonstrated that FLZ did not show any activity against C. albicans, whereas a combination of FLZ and Meth-Gin demonstrated greater activity as shown by the data of the zone of growth inhibition, MIC and time-kill assay. FLZ or Meth-Gin treatment could not completely cure VVC, whereas a combination of FLZ and Meth-Gin was greatly effective in the treatment of VVC. The vaginal tissue from mice of the infected control group had the highest fungal load of 155370 ± 20617 CFUs. Treatment with FLZ at a dose of 40 mg/kg reduced the fungal load to 120863 ± 10723 CFUs. Interestingly, the mice treated with a combination of FLZ (40 mg/kg) and Meth-Gin (200 mg/kg) had a fungal load of 256 ± 152 CFUs. Besides, FLZ and Meth-Gin combination effectively reduced the pro-inflammatory cytokines (IL-1β, TNF-α and IL-17) and the percentage of apoptotic cells in the vaginal tissues. Likewise, the histological analysis revealed the epithelial necrosis, shedding and ulceration in the vaginal tissue, whereas treatment with FLZ and Meth-Gin combination reversed the histopathological changes in the vaginal epithelium and lamina propria.

Conclusion: The findings of the current study suggest that the co-administration of Meth-Gin and FLZ may have a potential therapeutic effect in the treatment of azole-resistant candidiasis.

Keywords: candidiasis; cytokines; fluconazole; ginger extract; inflammation.

Grants and funding

This study is not supported by any funding agency.