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Antifungal activity and potential inhibitory mechanism of Huangqin decoction on Trichophyton mentagrophytes

ABSTRACT: Trichophyton mentagrophytes (T. mentagrophytes) is a prevalent pathogen that causes human and animal dermatophytosis. The clinical treatment of these infections is challenging due to the prolonged treatment duration, limited efficacy, antifungal resistance and side effects of existing drugs. It has been reported that the classic Traditional Chinese medicine (TCM) prescription Huangqin decoction (HQD) along with its principal ingredients could exhibit antifungal properties. Given the valued advantages of TCM such as broad-spectrum antifungal activity, low incidence of drug resistance and low toxicity, this study investigated the antifungal activity of HQD against T. mentagrophytes and explored the potential inhibitory mechanism, aimed to provide new clues for the treatment of dermatophytosis. By detecting minimal inhibitory concentration (MIC) using the broth microdilution method, the result showed that HQD could significantly inhibit the growth of T. mentagrophytes, with a MIC of 3.13 mg/mL. The transcriptome sequencing and quantitative real-time PCR (qRT-PCR) technology were combined to shed light on the complicated adaptive responses of T. mentagrophytes upon HQD. The results demonstrated that a total of 730 differentially expressed genes (DEGs) were detected in T. mentagrophytes after HQD exposure, of which 547 were up-regulated and 183 were down-regulated. These DEGs were abundant in “single-organism metabolic process”, “catalytic activity” and “oxidoreductase activity”, and were significantly enriched in seven signaling pathways including glutathione metabolism, DNA replication, glyoxylate and dicarboxylate metabolism, taurine and hypotaurine metabolism, carotenoid biosynthesis, ubiquitin mediated proteolysis, and cyanoamino acid metabolism. The results of transcriptome profiling were verified using qRT-PCR for a subset of 10 DEGs. The overall evidence indicated that HQD had a significant anti-dermatophyte activity through the modulation of glutathione metabolism by regulating GST, γ-GT genes, the inhibition of DNA replication pathway by downgrading MCM3, MCM5, RNaseH1 genes, and the repressed expression of PSD gene related to phospholipid synthesis in T. mentagrophytes.

ORGANISM(S): Trichophyton mentagrophytes

PROVIDER: GSE287990 | GEO | 2025/01/29

REPOSITORIES: GEO

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Project description:Purpose: The goal of this study is to identify the difference of immunity between wild-type and yellow mutant rainbow trout in natural flowing water pond culture environment. Methods: The transcriptomic profiles of the skin were generated by using the Hiseq™4000 sequencing platform. Results: A total of 557,976,332 clean reads were yielded from six libraries and then assembled into 38,226 genes. Using P-value of 0.05 as the threshold, 3373 differentially expressed genes (DEGs) were obtained between WR_S and YR_S rainbow trout skin including the members of HSP90, V-ATPases, GST, SUGT1, NLRP3, NOD1, TLR3, IFR3, DHX58, IFIH1, JAK1, JAK2, STAT1 and NAMPT (|log2 fold-change| ranged from 1 to 4). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of DEGs were performed. A majority of DEGs were enriched in innate immune-related GO terms and pathways, such as activation of innate immune response, inflammatory response, innate immune response, NAD+ADP-ribosyltransferase activity and NAD biosynthetic process in sub-categories of GO terms, and RIG-I-like receptor signaling pathway, NOD-like receptor signaling pathway, Toll-like receptor signaling pathway, Phagosome, Jak-STAT signaling pathway in KEGG enrichment pathways. Meanwhile, several immune-related metabolic pathways were also identified including metabolism of Xenobiotics by cytochrome P450, Glutathione metabolism, Nicotinate and nicotinamide metabolism. Additionally, 15 DEGs were selected and validated their expression level by qRT-PCR to confirm accuracy of the RNA-seq. Conclusions: Our study is the first time to clarify the skin innate immunity difference between wild-type and yellow mutant rainbow trout in the natural flowing water pond culture environment. Our results show that the expression of most immune-related genes in the corresponding pathways were up-regulated in WR_S rainbow trout. We presumed that the disease resistance of WR_S rainbow trout might be stronger than YR_S rainbow trout.

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Antifungal activity and potential inhibitory mechanism of Huangqin decoction on Trichophyton mentagrophytes

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