Huangqin Decoction Exerts Antifungal Effects by Interfering with Energy Metabolism of Trichophyton rubrum with Glyoxylate Cycle as a Potential Target
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PROVIDER: PRJNA1282973 | ENA |
REPOSITORIES: ENA
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Project description:Background: The dermatophyte Trichophyton rubrum (T. rubrum) is a highly specialized filamentous fungus that infects keratinized tissues and is the most common pathogen isolated from human dermatophytosis. The clinical treatment of the infections is challenging due to the prolonged treatment duration, limited efficacy, antifungal resistance and adverse effects of available drugs. Huangqin decoction (HQD) is a classical traditional Chinese medicine (TCM) formula, whose inhibitory efficiency against T. rubrum was disclosed in our previous study. However, the responsible mechanisms are not well understood. Aim: This study aimed to elucidate the mode of action of Huangqin decoction (HQD) against T. rubrum as a whole by using transcriptome sequencing combined with verification of qRT-PCR and enzymatic activity assays. Methods: By treating T. rubrum with HQD at minimum inhibitory concentration (MIC), the differentially expressed genes (DEGs) of T. rubrum in response to HQD based on transcriptome profiles were recognized. Gene function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed functions and signaling pathways modulated by the DEGs. The transcriptome results were validated by quantitative real-time PCR (qRT-PCR). The potential targets were further explored using enzymatic activity assays. Results: At MIC, a total of 338 differentially expressed genes (DEGs) were detected in T. rubrum after HQD exposure compared with the control group (q-value < 0.05), of which 199 genes were significantly up-regulated and 139 genes were down-regulated. Gene function analysis indicated that COG functions of DEGs mainly covered “carbohydrate transport and metabolism” and “energy production and conversion”. The most frequently found GO terms were “metabolic process” and “catalytic activity”. KEGG enrichment analysis revealed that DEGs were predominately enriched in 6 pathways of “valine, leucine and isoleucine degradation”, “indole alkaloid biosynthesis”, “ABC transporters”, “synthesis and degradation of ketone bodies”, “starch and sucrose metabolism”, and “glyoxylate and dicarboxylate metabolism” (q-value < 0.05). Three KEGG pathways were closely related to energy metabolism, which was consistent with the COG and GO results. A subset of eight DEGs by the involvement of the biosynthesis and degradation of cell walls and energy metabolism including amino acid metabolism and the glyoxylate cycle were further confirmed by qRT-PCR and the results verified the transcriptome data. Enzymatic activity assays showed that compared to the control group, activities of citrate synthase (CS), aconitate hydratase (ACO) and isocitrate lyase (ICL) in the glyoxylate cycle were affected by HQD. Conclusion: The overall evidence suggested that the interference of energy metabolism might contribute to the mode of action of HQD against dermatophyte pathogen T. rubrum, and the glyoxylate cycle may be the potential antifungal target of HQD against the fungi. Our study provides a theoretical basis for the mechanisms of HQD upon T. rubrum infections and offers an important insight regarding the glyoxylate cycle especially enzyme isocitrate lyase as indispensable targets of the herbal formulations.
2025-06-28 | GSE300994 | GEO
Project description: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.
2025-01-29 | GSE287990 | GEO
Project description:Antifungal activity and potential inhibitory mechanism of Huangqin decoction on Trichophyton mentagrophytes
| PRJNA1215414 | ENA
Project description:Influenza A viruses (IAVs), particularly H1N1, H5N1 and H7N9, pose a substantial threat to public health worldwide. Here, we report that MIR2911, a honeysuckle (HS)-encoded atypical microRNA, directly targets IAVs with a broad spectrum. MIR2911 is highly stable in HS decoction, and continuous drinking or gavage feeding of HS decoction leads to a significant elevation of the MIR2911 level in mouse peripheral blood and lung. Bioinformatics prediction and a luciferase reporter assay showed that MIR2911 could target various IAVs, including H1N1, H5N1 and H7N9. Synthetic MIR2911 significantly inhibited H1N1-encoded PB2 and NS1 protein expression but did not affect mutants in which the MIR2911-binding nucleotide sequences were altered. Synthetic MIR2911, extracted RNA from HS decoction and HS decoction all significantly inhibited H1N1 viral replication and improved viral infection-induced mouse weight loss but did not affect infection with a mutant virus in which the MIR2911-binding nucleotide sequences of PB2 and NS1 were altered. Importantly, the inhibitory effect of HS decoction on viral replication was abolished by an anti-MIR2911 antagomir, indicating that the physiological concentration of MIR2911 in HS decoction could directly and sufficiently suppress H1N1 viral replication. MIR2911 also inhibited H5N1 and H7N9 viral replication in vitro and in vivo. Strikingly, administration of MIR2911 or HS decoction both dramatically reduced mouse mortality caused by H5N1 infection. Our results demonstrate that MIR2911 is the first active component identified in Traditional Chinese Medicine to directly target various IAVs and may represent a novel type of natural product that effectively suppresses viral infection. Screening and profiling of known plant microRNA in HS and HS decoction
2014-10-22 | E-GEOD-55268 | biostudies-arrayexpress
Project description:Interventions: Experimental group:Sanwu Huangqin decoction;control group:placebo
Primary outcome(s): Recurrence rate of adenoma
Study Design: Parallel
| 2692741 | ecrin-mdr-crc
Project description:We aimed to investigate the syndrome of Sini decoction pattern. The Sini decoction was first mentioned in Shang Han Za Bing Lun, then was developed into Sini decoction pattern (SDP) by Sun Simiao’s Qian Jin Yi Fang. The syndromes of SDP were correlated with various extremely Yang deficiency related symptoms, but there does not exist common definition.
2015-03-20 | GSE67090 | GEO
Project description:Influenza A viruses (IAVs), particularly H1N1, H5N1 and H7N9, pose a substantial threat to public health worldwide. Here, we report that MIR2911, a honeysuckle (HS)-encoded atypical microRNA, directly targets IAVs with a broad spectrum. MIR2911 is highly stable in HS decoction, and continuous drinking or gavage feeding of HS decoction leads to a significant elevation of the MIR2911 level in mouse peripheral blood and lung. Bioinformatics prediction and a luciferase reporter assay showed that MIR2911 could target various IAVs, including H1N1, H5N1 and H7N9. Synthetic MIR2911 significantly inhibited H1N1-encoded PB2 and NS1 protein expression but did not affect mutants in which the MIR2911-binding nucleotide sequences were altered. Synthetic MIR2911, extracted RNA from HS decoction and HS decoction all significantly inhibited H1N1 viral replication and improved viral infection-induced mouse weight loss but did not affect infection with a mutant virus in which the MIR2911-binding nucleotide sequences of PB2 and NS1 were altered. Importantly, the inhibitory effect of HS decoction on viral replication was abolished by an anti-MIR2911 antagomir, indicating that the physiological concentration of MIR2911 in HS decoction could directly and sufficiently suppress H1N1 viral replication. MIR2911 also inhibited H5N1 and H7N9 viral replication in vitro and in vivo. Strikingly, administration of MIR2911 or HS decoction both dramatically reduced mouse mortality caused by H5N1 infection. Our results demonstrate that MIR2911 is the first active component identified in Traditional Chinese Medicine to directly target various IAVs and may represent a novel type of natural product that effectively suppresses viral infection.
2014-10-22 | GSE55268 | GEO
Project description:Resistance, tolerance and persistence enable pathogenic bacteria to survive antibiotic treatment and are associated with an elevated risk of treatment failure and relapsing infections. The mechanism underlying bacterial antibiotic persister formation is not well understood. Here, we show that glyoxylate, a metabolite originally evolved to allow bacteria to utilize alternative carbon sources for optimal growth and pathogenicity, also serves as a signaling molecule to alter host gene expression and support persister formation. Specifically, we discovered glyoxylate interacting with TET2 DNA dioxygenase through an in-silico screen of human metabolome. We further show that Salmonella-produced glyoxylate inhibits the activity of Tet2 to suppress the expression of pro-inflammatory genes and attenuate host immune defense. Catalytic inactivation of Tet2, by genetic knock-in mutation, glyoxylate production by Salmonella, or exogenous glyoxylate treatment, facilitates bacterial persister formation in both murine and human macrophages. Conversely, stimulating TET2 with vitamin C or blocking Salmonella production of glyoxylate counters bacterial antibiotic resistance and improves the infection treatment outcomes. In conclusion, our study reveals a novel signaling function of glyoxylate in gene regulation beyond energetic and biosynthetic metabolism. Our findings also suggest that stimulating TET activity within host cells represents a potential therapeutic strategy to combat bacterial persistence.
2025-11-01 | GSE281278 | GEO
Project description:Resistance, tolerance and persistence enable pathogenic bacteria to survive antibiotic treatment and are associated with an elevated risk of treatment failure and relapsing infections. The mechanism underlying bacterial antibiotic persister formation is not well understood. Here, we show that glyoxylate, a metabolite originally evolved to allow bacteria to utilize alternative carbon sources for optimal growth and pathogenicity, also serves as a signaling molecule to alter host gene expression and support persister formation. Specifically, we discovered glyoxylate interacting with TET2 DNA dioxygenase through an in-silico screen of human metabolome. We further show that Salmonella-produced glyoxylate inhibits the activity of Tet2 to suppress the expression of pro-inflammatory genes and attenuate host immune defense. Catalytic inactivation of Tet2, by genetic knock-in mutation, glyoxylate production by Salmonella, or exogenous glyoxylate treatment, facilitates bacterial persister formation in both murine and human macrophages. Conversely, stimulating TET2 with vitamin C or blocking Salmonella production of glyoxylate counters bacterial antibiotic resistance and improves the infection treatment outcomes. In conclusion, our study reveals a novel signaling function of glyoxylate in gene regulation beyond energetic and biosynthetic metabolism. Our findings also suggest that stimulating TET activity within host cells represents a potential therapeutic strategy to combat bacterial persistence.
2025-03-18 | GSE280758 | GEO