Skip to content
1887

Abstract

is a major causative agent of superficial dermatomycoses such as onychomycosis and tinea pedis. Huangqin decoction (HQD), as a classical traditional Chinese medicine formula, was found to inhibit the growth of common clinical dermatophytes such as in our previous drug susceptibility experiments.

The antifungal activity and potential mechanism of HQD against have not yet been investigated.

The aim of this study was to investigate the antifungal activity and explore the potential mechanism of action of HQD against .

The present study was performed to evaluate the antifungal activity of HQD against by determination of minimal inhibitory concentrations (MICs), minimal fungicidal concentrations (MFCs), mycelial growth, biomass, spore germination and structural damage, and explore its preliminary anti-dermatophyte mechanisms by sorbitol and ergosterol assay, HPLC-based ergosterol test, enzyme-linked immunosorbent assay and mitochondrial enzyme activity test.

HQD was able to inhibit the growth of significantly, with an MIC of 3.125 mg ml and an MFC of 12.5 mg ml. It also significantly inhibited the hyphal growth, conidia germination and biomass growth of in a dose-dependent manner, and induced structural damage in different degrees for cells. HQD showed no effect on cell wall integrity, but was able to damage the cell membrane of by interfering with ergosterol biosynthesis, involving the reduction of squalene epoxidase (SE) and sterol 14α-demethylase P450 (CYP51) activities, and also affect the malate dehydrogenase (MDH), succinate dehydrogenase (SDH) and ATPase activities of mitochondria.

These results revealed that HQD had significant anti-dermatophyte activity, which was associated with destroying the cell membrane and affecting the enzyme activities of mitochondria.

Funding
This study was supported by the:
  • the Science and technology plan project of Health Commission of Jiangxi Province (Award 202310011)
    • Principle Award Recipient: ChengyingShen
  • the Science and technology plan project of Jiangxi Province administration of traditional Chinese medicine (Award 2023B1311)
    • Principle Award Recipient: ChengyingShen
  • Natural Science Foundation of Jiangxi Province (Award 20232BAB216124)
    • Principle Award Recipient: ChengyingShen
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.001805
2024-02-13
2025-05-19
Loading full text...

Full text loading...

/deliver/fulltext/jmm/73/2/jmm001805.html?itemId=/content/journal/jmm/10.1099/jmm.0.001805&mimeType=html&fmt=ahah

References

  1. Pereira FO, Gomes SM, Silva SL, Teixeira AP, Lima IO. The prevalence of dermatophytoses in Brazil: a systematic review. J Med Microbiol 2021; 3:1
    [Google Scholar]
  2. Rouzaud C, Chosidow O, Brocard A, Fraitag S, Scemla A et al. Severe dermatophytosis in solid organ transplant recipients: a French retrospective series and literature review. Transpl Infect Dis 2018; 1:1 [View Article] [PubMed]
    [Google Scholar]
  3. Sun Y, Huang H, Chen J, Li J, Ma J et al. Invasive fungal infection in patients receiving chemotherapy for hematological malignancy: a multicenter, prospective, observational study in China. Tumour Biol 2015; 2:757–767 [View Article] [PubMed]
    [Google Scholar]
  4. Whittle SB, Williamson KC, Russell HV. Incidence and risk factors of bacterial and fungal infection during induction chemotherapy for high-risk neuroblastoma. Pediatr Hematol Oncol 2017; 5:331–342 [View Article] [PubMed]
    [Google Scholar]
  5. Ge S. Retrospective Epidemiological Study of Dermatophytosis in China and Pathogenic Differences Between Trichophyton Rubrum and Trichophyton Vio1aceum Peking Union Medical College; 2022
    [Google Scholar]
  6. Campoy S, Adrio JL. Antifungals. Biochem Pharmacol 2017; 133:86–96 [View Article] [PubMed]
    [Google Scholar]
  7. Perlin DS, Rautemaa-Richardson R, Alastruey-Izquierdo A. The global problem of antifungal resistance: prevalence, mechanisms, and management. Lancet Infect Dis 2017; 17:e383–e392 [View Article] [PubMed]
    [Google Scholar]
  8. Ben-Ami R, Kontoyiannis DP. Resistance to antifungal drugs. Infect Dis Clin North Am 2021; 2:279–311 [View Article] [PubMed]
    [Google Scholar]
  9. Liu X, Ma Z, Zhang J, Yang L. Antifungal compounds against Candida infections from traditional Chinese medicine. Biomed Res Int 2017; 2017:4614183 [View Article] [PubMed]
    [Google Scholar]
  10. Liu Q, Luyten W, Pellens K, Wang Y, Wang W et al. Antifungal activity in plants from Chinese traditional and folk medicine. J Ethnopharmacol 2012; 3:772–778 [View Article] [PubMed]
    [Google Scholar]
  11. Lopes G, Pinto E, Salgueiro L. Natural products: an alternative to conventional therapy for dermatophytosis?. Mycopathologia 2017; 182:143–167 [View Article] [PubMed]
    [Google Scholar]
  12. Li M-Y, Li M-X, Xu N, Li Z-H, Zhang Y-M et al. Effects of Huangqin decoction on ulcerative colitis by targeting estrogen receptor alpha and ameliorating endothelial dysfunction based on system pharmacology. J Ethnopharmacol 2021; 271:113886 [View Article] [PubMed]
    [Google Scholar]
  13. Li M-Y, Luo H-J, Wu X, Liu Y-H, Gan Y-X et al. Anti-inflammatory effects of Huangqin decoction on dextran sulfate sodium-induced ulcerative colitis in mice through regulation of the gut microbiota and suppression of the Ras-PI3K-Akt-HIF-1α and NF-κB pathways. Front Pharmacol 2020; 10:1552 [View Article] [PubMed]
    [Google Scholar]
  14. Yan B-F, Wang Y, Wang W-B, Ding X-J, Wei B et al. Huangqin decoction mitigates hepatic inflammation in high-fat diet-challenged rats by inhibiting TLR4/NF-κB/NLRP3 pathway. J Ethnopharmacol 2023; 303:115999 [View Article] [PubMed]
    [Google Scholar]
  15. Chen P, Zhou X, Zhang L, Shan M, Bao B et al. Anti-inflammatory effects of Huangqin tang extract in mice on ulcerative colitis. J Ethnopharmacol 2015; 162:207–214 [View Article] [PubMed]
    [Google Scholar]
  16. Yan M, Zuo F, Song H, Ye W, Zhou Z. Comparative study on antibacterial effects of huangqin-tang and its metabolites produced by intestinal flora. Zhongguo Zhong Yao Za Zhi 2003; 3:243–246 [PubMed]
    [Google Scholar]
  17. Wang J, Li R, Zhang M, Gu C, Wang H et al. Influence of Huangqin decoction on the immune function and fecal microbiome of chicks after experimental infection with Escherichia coli O78. Sci Rep 2022; 1:16632 [View Article] [PubMed]
    [Google Scholar]
  18. Zuo F, Zhou ZM, Liu ML. Determination of 14 chemical constituents in the traditional Chinese medicinal preparation Huangqin-Tang by high performance liquid chromatography. Biol Pharm Bull 2001; 6:693–697 [View Article] [PubMed]
    [Google Scholar]
  19. Wang T, Shi G, Shao J, Wu D, Yan Y et al. In vitro antifungal activity of baicalin against Candida albicans biofilms via apoptotic induction. Microb Pathog 2015; 87:21–29 [View Article] [PubMed]
    [Google Scholar]
  20. Da X, Nishiyama Y, Tie D, Hein KZ, Yamamoto O et al. Antifungal activity and mechanism of action of Ou-gon (Scutellaria root extract) components against pathogenic fungi. Sci Rep 2019; 1:1683 [View Article] [PubMed]
    [Google Scholar]
  21. Wang DM, Wang JP, Yang JY, Zhang HM, Liu SH. Paeoniflorin effects on Candida albicans biofilms. Chin J Tissue Eng Res 2014; 25:4038–4042
    [Google Scholar]
  22. Sharifi-Rad J, Quispe C, Herrera-Bravo J, Belén LH, Kaur R et al. Glycyrrhiza genus: enlightening phytochemical components for pharmacological and health-promoting abilities. Oxid Med Cell Longev 2021; 2021:7571132 [View Article] [PubMed]
    [Google Scholar]
  23. Shen CY, Deng FY, Hou XJ, Xiong Y, Zhan P et al. In vitro observation of antifungal effect of Huangqin decoction against common clinical fungi. Pharm J Chin PLA 2022; 6:479–481
    [Google Scholar]
  24. Blechert O, Mei H, Zang X, Zheng H, Liang G et al. Auxotrophic mutations of Trichophyton rubrum created by in vitro synthesized Cas9 ribonucleoprotein. BMC Biotechnol 2020; 1:6 [View Article] [PubMed]
    [Google Scholar]
  25. Shen CY, Wu WM, Hou XJ, Deng FY, He J et al. Fingerprint establishment of Huangqin decoction and study on spectrum-effect relationship of its antidermatophytic activity in different phase states. China Pharmacy 2023; 6:687–691
    [Google Scholar]
  26. Clinical and Laboratory Standards Institute (CLSI) Reference Method for Broth Dilution Antifungal Susceptibility Testing of Filamentous Fungi. In CLSI Standard M38 (ISBN 1-56238-830-4 [Print]; ISBN 1-56238-831-2 [Electronic]), 3rd. edn Wayne, Pennsylvania 19087 USA: Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500; 2017 [PubMed]
    [Google Scholar]
  27. Ye L, Lin P, Du W, Wang Y, Tang C et al. Preparation, antidermatophyte activity, and mechanism of methylphloroglucinol derivatives. Front Microbiol 2018; 9:2262 [View Article] [PubMed]
    [Google Scholar]
  28. Luo N, Jin L, Yang C, Zhu Y, Ye X et al. Antifungal activity and potential mechanism of magnoflorine against Trichophyton rubrum. J Antibiot 2021; 3:206–214 [View Article] [PubMed]
    [Google Scholar]
  29. de Oliveira Lima MI, Araújo de Medeiros AC, Souza Silva KV, Cardoso GN, de Oliveira Lima E et al. Investigation of the antifungal potential of linalool against clinical isolates of fluconazole resistant Trichophyton rubrum. J Mycol Med 2017; 2:195–202 [View Article] [PubMed]
    [Google Scholar]
  30. Zeng H, Chen XP, Liang JN. In vitro antifungal activity and mechanism of essential oil from fennel (Foeniculum vulgare L.) on dermatophyte species. J Med Microbiol 2015; 1:93–103 [View Article] [PubMed]
    [Google Scholar]
  31. Lin H, Liu X, Shen Z, Cheng W, Zeng Z et al. The effect of isoflavaspidic acid PB extracted from Dryopteris fragrans (L.) Schott on planktonic and biofilm growth of dermatophytes and the possible mechanism of antibiofilm. J Ethnopharmacol 2019; 241:111956 [View Article] [PubMed]
    [Google Scholar]
  32. Hu YC, Zhang JM, Kong WJ, Zhao G, Yang MH. Mechanisms of antifungal and anti-aflatoxigenic properties of essential oil derived from turmeric (Curcuma longa L.) on Aspergillus flavus. Food Chem 2017; 220:1–8 [View Article] [PubMed]
    [Google Scholar]
  33. Zhang SW, Wu ZM, Yang Y, Li KT. Antifungal action of antifungalmycin N2 against Rhizoctonia solani by disrupting cell membrane and inhibiting succinate dehydrogenase. Curr Microbiol 2020; 2:254–260 [View Article] [PubMed]
    [Google Scholar]
  34. Lee WJ, Kim SL, Jang YH, Lee S-J, Kim DW et al. Increasing prevalence of Trichophyton rubrum identified through an analysis of 115,846 cases over the Last 37 years. J Korean Med Sci 2015; 30:639–643 [View Article] [PubMed]
    [Google Scholar]
  35. Nivoix Y, Ledoux MP, Herbrecht R. Antifungal therapy: new and evolving therapies. Semin Respir Crit Care Med 2020; 1:158–174 [View Article] [PubMed]
    [Google Scholar]
  36. Santo RD. Recent developments in antifungal drug discovery. Annu Rep Med Chem 2006; 41:299–315
    [Google Scholar]
  37. Szymański M, Chmielewska S, Czyżewska U, Malinowska M, Tylicki A. Echinocandins - structure, mechanism of action and use in antifungal therapy. J Enzyme Inhib Med Chem 2022; 1:876–894 [View Article] [PubMed]
    [Google Scholar]
  38. Chaudhary PM, Tupe SG, Deshpande MV. Chitin synthase inhibitors as antifungal agents. Mini Rev Med Chem 2013; 2:222–236 [View Article] [PubMed]
    [Google Scholar]
  39. Bowman SM, Free SJ. The structure and synthesis of the fungal cell wall. Bioessays 2006; 8:799–808 [View Article] [PubMed]
    [Google Scholar]
  40. de Oliveira Pereira F, Mendes JM, de Oliveira Lima E. Investigation on mechanism of antifungal activity of eugenol against Trichophyton rubrum. Med Mycol 2013; 5:507–513 [View Article] [PubMed]
    [Google Scholar]
  41. Zhang Z, Liu X, Shen Z, Chen Y, Chen C et al. Isoflavaspidic acid PB extracted from Dryopteris fragrans (L.) Schott inhibits Trichophyton rubrum growth via membrane permeability alternation and ergosterol biosynthesis disruption. Biomed Res Int 2022; 2022:6230193 [View Article] [PubMed]
    [Google Scholar]
  42. Lee HS, Kim Y. Aucklandia lappa causes cell wall damage in Candida albicans by reducing chitin and (1,3)-β-D-glucan. J Microbiol Biotechnol 2020; 7:967–973 [View Article] [PubMed]
    [Google Scholar]
  43. Curto , Butassi E, Ribas JC, Svetaz LA, Cortés JCG. Natural products targeting the synthesis of β(1,3)-D-glucan and chitin of the fungal cell wall. Existing drugs and recent findings. Phytomedicine 2021; 88:153556 [View Article] [PubMed]
    [Google Scholar]
  44. Zheng Y, Shang YH, Li MY, Li YZ, Ouyang WQ. Antifungal activities of cis-trans citral isomers against Trichophyton rubrum with ERG6 as a potential target. Molecules 2021; 14:4263 [View Article]
    [Google Scholar]
  45. An Y, Liu W, Xie H, Fan H, Han J et al. Construction and activity evaluation of novel benzodioxane derivatives as dual-target antifungal inhibitors. Eur J Med Chem 2022; 227:113950 [View Article] [PubMed]
    [Google Scholar]
  46. Wu XZ, Cheng AX, Sun LM, Sun SJ, Lou HX. Plagiochin E, an antifungal bis(bibenzyl), exerts its antifungal activity through mitochondrial dysfunction-induced reactive oxygen species accumulation in Candida albicans. Biochim Biophys Acta 2009; 8:770–777 [View Article] [PubMed]
    [Google Scholar]
  47. Li Y, Shao X, Xu J, Wei Y, Xu F et al. Tea tree oil exhibits antifungal activity against Botrytis cinerea by affecting mitochondria. Food Chem 2017; 234:62–67 [View Article] [PubMed]
    [Google Scholar]
/content/journal/jmm/10.1099/jmm.0.001805
Loading
/content/journal/jmm/10.1099/jmm.0.001805
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error