Antifungal Mechanisms of a Chinese Herbal Medicine, Cao Huang Gui Xiang, Against Candida Species

Yue, Huizhen; Xu, Xiaolong; He, Shasha; Cui, Xuran; Guo, Yuhong; Zhao, Jingxia; Peng, Boya; Liu, Qingquan

doi:10.3389/fphar.2022.813818

Cited by 3 publications

(2 citation statements)

References 44 publications

(66 reference statements)

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“…C. albicans is a major opportunistic human pathogen that can reside in the oral cavity, intestinal tract, and vaginal area as a commensal microbiota. When patients are subjected to long-term broad-spectrum antibiotics, chemotherapies, or have weakened immune systems, they develop both superficial maladies and potentially fatal disseminated infections ( Yue et al, 2022 ). Furthermore, C. albicans can easily form biofilm, making these organisms difficult to treat.…”

Section: Discussionmentioning

confidence: 99%

A semi purified hydroalcoholic fraction from Caesalpinia bonduc seeds causes ergosterol biosynthesis inhibition in Candida albicans resulting in cell membrane damage

Sasidharan¹,

Nishanth²,

Nair³

2023

Front. Pharmacol.

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Candida species are currently developing resistance to prevailing commercially available drugs, which raises an instantaneous need to discover novel antifungals. To cope with this shocking situation, phytochemicals are the richest, safest, and most potent source of excellent antimicrobials with broad-spectrum activity. The aim of the current study is to explore the anticandidal potential of the various fractions purified from the hydroalcoholic extract of C. bonduc seed. Out of five fractions purified from the hydroalcoholic extract, fraction 3 (Fr. 3) recorded the best activity against C. albicans (8 μg/mL) and thus this species was chosen for further mechanism of action studies. The phytochemical examination reveals that Fr. 3 was found to contain steroids and triterpenoids. This was further supported by LC-QTOF-MS and GCMS analyses. Our findings show that Fr. 3 targets the ergosterol biosynthesis pathway in C. albicans by inhibiting the lanosterol 14-α demethylase enzyme and downregulating expression of its related gene ERG11. Molecular docking outcomes disclosed favorable structural dynamics of the compounds, implying that the compounds present in Fr. 3 would be able to successfully bind to the lanosterol 14-α demethylase, as evidenced by the docked compounds’ strong interaction with the target enzyme’s amino acid residues. Considering virulence factors, the Fr. 3 recorded significant antibiofilm activity as well as germ-tube reduction potential. Furthermore, Fr. 3 enhances the production of intracellular reactive oxygen species (ROS). This suggests that the antifungal activity of Fr. 3 was associated with membrane damage and the induction of ROS production, resulting in cell death. Fluorescence microscopic analysis of PI stained Candida further showed changes in the plasma membrane permeability, which causes severe loss of intracellular material and osmotic balance. This was demonstrated by the potassium ion leakage and release of genetic materials. Finally, the erythrocyte lysis assay confirmed the low cytotoxicity of Fr. 3. Both in silico and in vitro results suggest that Fr. 3 has the potential to propel forward novel antifungal drug discovery programmes.

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Section: Discussionmentioning

confidence: 99%

A semi purified hydroalcoholic fraction from Caesalpinia bonduc seeds causes ergosterol biosynthesis inhibition in Candida albicans resulting in cell membrane damage

Sasidharan¹,

Nishanth²,

Nair³

2023

Front. Pharmacol.

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“…Ultra-performance liquid chromatography-tandem mass spectrometry of Qin-Qiao-Xiao-Du formula Plasma samples were collected at 30, 60, and 90 min after oral administration of QQXD decoction for 5 days. A system (Waters Corp., Milford, MA, United States) equipped with a HESI-II probe was used to identify the main components of QQXD, as previously reported (31). The positive and negative HESI-II voltages were set to 3.5 and -3.0 kV, respectively, and the vaporizer temperature was set to 400 • C. Both sheath gas and auxiliary gas are nitrogen, and collision gas is high-purity nitrogen.…”

Section: Introductionmentioning

confidence: 99%

Qin-Qiao-Xiao-Du formula alleviate influenza virus infectious pneumonia through regulation gut microbiota and metabolomics

Lian

Jiang

et al. 2022

Front. Med.

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Qin-Qiao-Xiao-Du (QQXD), a traditional Chinese medicine (TCM) formula, has been used in the clinical treatment of influenza virus pneumonia. However, the effects and mechanisms of QQXD on influenza virus pneumonia remain unknown. Therefore, this study explores the mechanisms of QQXD in the treatment of influenza virus pneumonia from the point of view of intestinal flora and metabolism. The results showed that QQXD was able to reduce mortality, weight loss, lung viral load, lung index, and lung injury in influenza virus mice. A cytokine array found that the QQXD attenuated the expression of serum IL-1α, IL-4, IL-12(P70), and TNF-α. Subsequently, 16s rRNA gene sequencing showed that QQXD could increase the relative abundances of Gemmiger, Anaerofustis, Adlercreutzia, and Streptococcus and decrease those of Dehalobacteriu, Burkholderia, Prevotella, Butyrimimonas, Delftia, and others. Meanwhile, targeted metabolic profiling analysis showed that QQXD could regulate nitrogen metabolism, phenylalanine metabolism, valine, leucine, and isoleucine biosynthesis. Correlation analysis demonstrated that the regulatory effect of QQXD on the cyanoamino acid metabolism pathway was associated with changes in the abundance of Parabacteroides, Pediococcus, and Clostridium in influenza mice. In conclusion, our study revealed that QQXD can inhibit influenza virus replication, suppress cytokine storms, and protect mice from influenza virus infection pneumonia. The mechanisms are likely to be related to improved gut microbiota dysbiosis, increased intestinal carbohydrate metabolism, and up-regulated cyanoamino acid metabolism pathways.

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Antifungal Activity of the Dichloromethane Extract of CaoHuangGuiXiang Formula Against Candida auris by in vitro and in vivo Evaluation

Yue,

Xu,

Peng

et al. 2024

IDR

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Purpose CaoHuangGuiXiang (CHGX) formula is a traditional Chinese medicine for the treatment of Candida -related infection. However, its antifungal mechanisms against the emerging fungal pathogen Candida auris remain unclear. This study aimed to evaluate the antifungal activity of the dichloromethane extract of CHGX (CHGX-DME) and clarified its antifungal mechanims against C. auris . Methods The major components of CHGX-DME were identified by ultra-performance liquid chromatography tandem mass spectrometry. Then, the minimal inhibitory concentration (MIC) assay and the time-kill kinetic assay were performed to investigate the in vitro antifungal activity of CHGX-DME against C. auris , including 8 isolates of 4 discrete clades and 2 special phenotypes (filamentous and aggregative). Furthermore, the effect of CHGX-DME on biofilm development was examined. In addition, the in vivo toxicity and efficacy of CHGX-DME were evaluated in a Galleria mellonella infection model. Results First, 20 major compounds in CHGX-DME were detected and characterized. The MIC 50% and MIC 90% of CHGX-DME against C. auris isolates ranged from 50–200 mg/L and 100–400 mg/L, respectively. At 400 mg/L, CHGX-DME was able to efficiently kill more than 70% and 90% of C. auris cells after 3 hours and 6 hours of treatment, respectively. This notable antifungal activity exhibited a dosage- and time-dependent manner. Moreover, CHGX-DME not only played a critical role in inhibiting the proliferation of filamentous and aggregative cells, but also showed restricting effect on biofilm development in C. auris . Importantly, it significantly improved the survival rate and reduced the fungal burden in G. mellonella infection models, suggesting a remarkable treatment effect against C. auris infection. Conclusion CHGX-DME exhibited potent antifungal activity against C. auris and significantly ameliorated this fungal infection in the G. mellonella model, confirming that it would be a promising antifungal drug for the troublesome and emerging fungal pathogen C. auris .

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Antifungal Mechanisms of a Chinese Herbal Medicine, Cao Huang Gui Xiang, Against Candida Species

Cited by 3 publications

References 44 publications

A semi purified hydroalcoholic fraction from Caesalpinia bonduc seeds causes ergosterol biosynthesis inhibition in Candida albicans resulting in cell membrane damage

A semi purified hydroalcoholic fraction from Caesalpinia bonduc seeds causes ergosterol biosynthesis inhibition in Candida albicans resulting in cell membrane damage

Qin-Qiao-Xiao-Du formula alleviate influenza virus infectious pneumonia through regulation gut microbiota and metabolomics

Antifungal Activity of the Dichloromethane Extract of CaoHuangGuiXiang Formula Against Candida auris by in vitro and in vivo Evaluation

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