Abstract
Background The invasive pulmonary aspergillosis is a kind of high incidence of disease with difficulties in treatment, poor prognosis, and high mortality. Objectives The study aimed to reveal the effect of cinnamaldehyde on the fungal cell wall and verify its efficacy on invasive pulmonary aspergillosis on immunosuppressed Institute of Cancer Research mice (ICR mice). Methods ICR mice were given cyclophosphamide 200 mg.kg−1. d−1 by intraperitoneal injection for 2 days. On the 4th day, the mice were given 50 μL of Aspergillosis fumigatus spore (107colony form unit CFU/mL) by intranasal injection to establish immunosuppressive animal models with invasive Aspergillosis fumigatus infection. Then the mice in treatment group orally administered cinnamaldehyde for 14 consecutive days, while voriconazole was given to the mice in the positive control group. Results The clearance rate of pulmonary fungi, cure rate, and reduction of 1,3-β-D-glucans in treatment group were 80.00%, 80.00%, and 81.00%, respectively while in positive control group they were 67.00%, 60.00%, and 62.00%, respectively. There were significant differences in the results between two groups as mentioned above (P<0.05). Electron microscopy showed that, in treatment group, the cell wall of Aspergillus fumigatus was dissolved and detached and the cell surface was incomplete. There were edema, degeneration, and necrosis in nucleus and organelle, which lead to cellular necrocytosis. The cytomembrane of Aspergillus fumigatus was intact, clear, and complete, whereas the cytomembrane in the positive control group disappeared. The hyphal morphology of Aspergillus fumigatus was deformed, but the cell wall was intact. Conclusion Cinnamaldehyde has a good curative effect in the treatment of invasive pulmonary aspergillus infection in immunodeficient mice. It mainly affects the synthesis of 1,3-β-D-glucans from the cytoderm of Aspergillus fumigatus but does not affect cell wall. It would potentially be an effective and novel drug for targeted treatment of Aspergillus fumigatus deep infection.
Highlights
Invasive pulmonary aspergillosis infection combined with immunodeficiency is a kind of disease with difficulties in treatment, a poor prognosis, and 80-90% of mortality rate [1, 2]
The results demonstrated that cinnamaldehyde inhibited 1,3-β-D-glucans synthesis in pulmonary tissues, destroyed the integrity of fungal cell wall, and exerted antibacterial effects, including cell wall dissolution and cell lysis, and therapeutic effects
The nucleus and contents completely dissolved and disappeared, forming vacuoles, but the cell membrane remained clear and intact. (Figures 7 and 8).The results suggested that cinnamaldehyde first acted on the outer layer of the cell wall of A. fumigatus, interfering with the (1,3)beta-D-glucan synthesis of the cell wall and damaging the skeletal structure and main antigenic components of the cell wall, but it did not affect the cell membrane
Summary
Invasive pulmonary aspergillosis infection combined with immunodeficiency is a kind of disease with difficulties in treatment, a poor prognosis, and 80-90% of mortality rate [1, 2]. Cinnamaldehyde has a good curative effect in the treatment of invasive pulmonary aspergillus infection in immunodeficient mice. It mainly affects the synthesis of 1,3-β-D-glucans from the cytoderm of Aspergillus fumigatus but does not affect cell wall. It would potentially be an effective and novel drug for targeted treatment of Aspergillus fumigatus deep infection
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