Prophylactic potential of Astragalus membranaceus extract in experimental pulmonary Candidiasis in Albino rats

Invasive candidiasis is a fungal infection with potentially serious outcomes, requiring novel therapies to overcome drug resistance. Astragalus membranaceus (AM) dried root extract has been shown to have anti-inflammatory and immunomodulatory properties. This study aimed to examine the anticandidal potential of AM versus fluconazole and explore the mechanisms underlying the antifungal effect in a model of lung candidiasis. Four groups (n = 6, in each) of twenty-four mature male Wistar albino rats were created: non-infected control, Candida-infected, AM-treated, and fluconazole-treated groups. Lung candidiasis was induced by a single intravenous inoculation of Candida albicans on the 10th day. In AM- and fluconazole-treated groups, the infected rats received AM extract (1000 mg/kg/day) and fluconazole (10 mg/kg/day) orally for 11 days. On day 12, the animals were sacrificed, and the lung tissues were harvested for microbiological, biochemical, and histological analyses. Lung tissue homogenates were subjected to ELISA and polymerase chain reaction (PCR)-based measurement of IL-1β, IL-4, IL-6, IL-10, IL-12, and TNF-α. Also, immunohistochemistry of NF-κB and i-NOS was conducted. In vitro evaluation using disc diffusion and minimum inhibitory concentration assays were used to evaluate AM's antifungal efficacy. AM improved lung histology, reduced the pulmonary fungal load, decreased lung cytokine levels, and increased the lung tissue levels of IL-12, compared to the infected group. Also, AM increased the iNOS expression at gene and protein levels, meanwhile downregulated NF-κB, in comparison with the infected group. In summary, AM protected against the lung damage caused by Candida, possibly by modulating the inflammatory response and NF-κB/IL-12/iNOS signaling pathway.