Therapeutic potential of Calotropis gigantea extract against invasive pulmonary aspergillosis: In vitro and in vivo study

• Published in: Asian Pacific Journal of Tropical Biomedicine
• Main Authors: Enas M Ali, Manal A Alfwuaires, Gehan M Badr
• Format: Article in Journal/Newspaper
• Language: English
• Published: Wolters Kluwer Medknow Publications 2022
• Subjects: aspergillus fumigatus; antifungal; invasive pulmonary aspergillosis; calotropis gigantea; amphotericin b; mice; Arctic medicine. Tropical medicine; RC955-962; Biology (General); QH301-705.5; Arctic
• Online Access: https://doi.org/10.4103/2221-1691.345516; https://doaj.org/article/a3f69e6b404f48cb872d686e0999a046

Objective: To characterize the antifungal activity of methanolic leaf extract of Calotropis gigantea alone or in combination with amphotericin B against invasive pulmonary aspergillosis in mice. Methods: GC/MS was used for analysis of active constituents of Calotropis gigantea extract. Spore germination assay and broth micro-dilution method were used to determine antifungal potential of Calotropis gigantea/amphotericin B against Aspergillus fumigatus. Neutropenic mice were randomly assigned into 5 groups: group 1 was neutropenic (control); group 2 was infected with Aspergillus fumigatus; group 3 was infected with Aspergillus fumigatus, and treated with Calotropis gigantea extract; group 4 was infected with Aspergillus fumigatus and treated with amphotericin B; group 5 was infected with Aspergillus fumigatus and treated with both Calotropis gigantea extract and amphotericin B. Fresh lung tissues were histopathologically examined. Fungal burden and gliotoxin concentration were evaluated in lung tissues. Catalase, superoxide dismutase, and malondialdehyde content were determined in lung tissues. Myeloperoxidase, tumor necrosis factor-alpha, interleukin-1, and interleukin-17 were also estimated by the sandwich enzyme-linked immuno-sorbent assay. Results: Calotropis gigantea/amphotericin B had a minimum inhibitory concentration and minimum fungicidal concentration of 80 and 160 μg/mL, respectively, for Aspergillus fumigatus. Additionally, Calotropis gigantea/amphotericin B significantly reduced lung fungal burden by 72.95% and inhibited production of gliotoxin in lung tissues from 6 320 to 1 350 μg/g lung. Calotropis gigantea/amphotericin B reduced the oxidative stress of the lung via elevating the activity of antioxidant enzymes and decreasing the levels of lipid peroxidation. Myeloperoxidase activity and the production of pro-inflammatory cytokines were also significantly reduced. Scanning electron microscopy revealed deteriorations in the hyphae ultrastructure in Calotropis gigantea/amphotericin B treated ...