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Inhibitory Effects of Berberine Hydrochloride on Trichophyton mentagrophytes and the Underlying Mechanisms.

ABSTRACT: BACKGROUND:T. mentagrophytes can infect all mammals, including rabbits, causing serious infections with remarkable economic losses for rabbit farmers. Berberine is an alkaloid that is effective against a variety of microbial infections such as T. mentagrophytes. Growth curve by dry weight determination and in-vivo antifungal assay were carried out to clarify the inhibitory effect of berberine hydrochloride against T. mentagrophytes. Transcriptomics analyses were also carried out for better understanding of the underlying mechanisms. RESULTS:The growth rate of T. mentagrophytes was significantly higher in control condition than under berberine hydrochloride or clotrimazole for 60 h. The growth rate of T. mentagrophytes was significantly slighter higher in berberine condition (1 mg) than under clotrimazole for 46 h. T. mentagrophytes seriously shrunk after berberine or clotrimazole treatment, as observed by TEM and in SEM. Significant recovery was evident in three berberine groups on day 6 compared with the DMSO group. Results from transcriptomics analyses showed 18,881 identified unigenes, including 18,754 and 12,127 in the NT and SwissProt databases. Among these, 12,011, 9174, and 11,679 unigenes belonged to 3 Gene Ontology (GO), 43 KEGG, and 25 KOG categories, respectively. Interestingly, we found that down-regulation of 14?-demethylase exposed to various medicines was slightly different, i.e., berberine hydrochloride (fold change -3.4956) and clotrimazole (fold change -2.1283) caused various degrees of alteration. CONCLUSIONS:Berberine hydrochloride could inhibit the growth of T. mentagrophytes. Berberine hydrochloride could also cure dermatosis induced by T. mentagrophytes. Down-regulation of 14?-demethylase exposed to various medicines was slightly different and might be one of the anti-resistance mechanisms of berberine hydrochloride in T. mentagrophytes. The present investigation provides considerable transcript sequence data that would help further assess the antifungal mechanisms against T. mentagrophytes, for antifungal medicine development.

SUBMITTER: Xiao CW

PROVIDER: S-EPMC6412246 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Inhibitory Effects of Berberine Hydrochloride on <i>Trichophyton mentagrophytes</i> and the Underlying Mechanisms.

Xiao Chen Wen CW Liu Yan Y Wei Qiang Q Ji Quan An QA Li Ke K Pan Li Jun LJ Bao Guo Lian GL

Molecules (Basel, Switzerland) 20190219 4

<h4>Background</h4><i>T. mentagrophytes</i> can infect all mammals, including rabbits, causing serious infections with remarkable economic losses for rabbit farmers. Berberine is an alkaloid that is effective against a variety of microbial infections such as <i>T. mentagrophytes</i>. Growth curve by dry weight determination and in-vivo antifungal assay were carried out to clarify the inhibitory effect of berberine hydrochloride against <i>T. mentagrophytes</i>. Transcriptomics analyses were also ...[more]

PMID: 30791402

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Project description:BackgroundRabbit breeding has developed into a large-scale industry, and as such, the incidence of dermatophytosis in rabbits has become increasingly common. A rabbit model with Trichophyton mentagrophytes infection was established to study the changes within the immune responses after fungal infection.MethodsAfter the T. mentagrophytes challenge on skin, pathogens on the skin were isolated from the rabbits in the fungal infection (FI) groups 20 days. Fungal observation under microscope were carried out. Identification of strains was achieved by polymerase chain reaction (PCR) using the CDR1 gene. The collected anticoagulant blood samples were analyzed for various blood cell parameters. The levels of antibodies, including IgM and IgA, cytokines, including IL-2, IL-6, and macrophage colony-stimulating factor (M-CSF), and soluble CD4 and CD8 in the serum of the FI group vs. the control group were determined independently. RNA isolation from blood samples and fluorescence-based quantitative PCR were carried out for the mRNA level of M-csf 20 days after fungal challenge.ResultsOur model resulted in typical symptoms of dermatophytosis on rabbit skin after challenged with fungus. Pathogens isolated from the infected rabbit skin were confirmed to be T. mentagrophytes by microscopic examination and PCR. The number of lymphocytes in the blood of the FI group was significantly decreased in comparison to the control group 2 days after the fungal challenge, but was significantly increased in comparison the control group 10 days after the fungal challenge (P < 0.01). Platelet counts of the FI group were significantly higher than in the control group at 2 (P < 0.05), 10 (P < 0.05), and 20 (P < 0.01) days after fungal challenge. The red blood cell distribution width of the FI group was significantly increased in comparison to that of the control group at 2, 10, and 20 days after fungal challenge (P < 0.01 for all days). The levels of antibodies (immunoglobulin (Ig) M and IgA (P < 0.01)), cytokines (interleukin (IL)-6 (P < 0.01), macrophage colony-stimulating factor (M-CSF) (P < 0.05)), and soluble CD4 (P < 0.01) and CD8 (P < 0.01) in the serum were significantly different between the FI and control groups. Serum M-csf mRNA level of the FI group was significantly higher than the control group 20 days after fungal challenge (P < 0.01).ConclusionsThis study demonstrates how the immune system responds to infection with T. mentagrophytes and provides potential targets for the prevention and treatment of dermatophytosis.

Dataset Information

Inhibitory Effects of Berberine Hydrochloride on Trichophyton mentagrophytes and the Underlying Mechanisms.

Publications

Inhibitory Effects of Berberine Hydrochloride on <i>Trichophyton mentagrophytes</i> and the Underlying Mechanisms.

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