iTRAQ-based proteomics revealed baicalein enhanced oxidative stress of <i>Candida albicans</i> by upregulating <i>CPD2</i> expression

Lv, Quanzhen; Xl, Zhang; Yan, Lan; Yy, Jiang

doi:10.1093/mmy/myac053

Cited by 4 publications

(3 citation statements)

References 38 publications

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“…In addition, Lv's work shows that BE enhances the oxidative stress effect of C. albicans by upregulating the expression of CPD2, thereby triggering oxidative damage and apoptosis in fungus [60]. These results also suggest that there could be multiple targets for BE.…”

Section: Discussionmentioning

confidence: 93%

Exploration of Baicalein-Core Derivatives as Potent Antifungal Agents: SAR and Mechanism Insights

Zhou,

Yang,

et al. 2023

Molecules

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Baicalein (BE), the major component of Scutellaria Baicalensis, exhibited potently antifungal activity against drug-resistant Candida albicans, and strong inhibition on biofilm formation. Therefore, a series of baicalein-core derivatives were designed and synthesized to find more potent compounds and investigate structure–activity relationship (SAR) and mode of action (MoA). Results demonstrate that A4 and B5 exert a more potent antifungal effect (MIC80 = 0.125 μg/mL) than BE (MIC80 = 4 μg/mL) when used in combination with fluconazole (FLC), while the MIC80 of FLC dropped from 128 μg/mL to 1 μg/mL. SAR analysis indicates that the presence of 5-OH is crucial for synergistic antifungal activities, while o-dihydroxyls and vic-trihydroxyls are an essential pharmacophore, whether they are located on the A ring or the B ring of flavonoids. The MoA demonstrated that these compounds exhibited potent antifungal effects by inhibiting hypha formation of C. albicans. However, sterol composition assay and enzymatic assay conducted in vitro indicated minimal impact of these compounds on sterol biosynthesis and Eno1. These findings were further confirmed by the results of the in-silico assay, which assessed the stability of the complexes. Moreover, the inhibition of hypha of this kind of compound could be attributed to their effect on the catalytic subunit of 1,3-β-d-glucan synthase, 1,3-β-d-glucan-UDP glucosyltransferase and glycosyl-phosphatidylinositol protein, rather than inhibiting ergosterol biosynthesis and Eno1 activity by Induced-Fit Docking and Molecular Dynamics Simulations. This study presents potential antifungal agents with synergistic effects that can effectively inhibit hypha formation. It also provides new insights into the MoA.

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Section: Discussionmentioning

confidence: 93%

Exploration of Baicalein-Core Derivatives as Potent Antifungal Agents: SAR and Mechanism Insights

Zhou,

Yang,

et al. 2023

Molecules

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“…protein of the strain and induce the programmed cell death of the strain (Lv et al, 2022;Ma et al, 2023a). In the cell, ROS is mainly produced by mitochondria, and the rate of ROS production by mitochondria is mainly regulated by the transmembrane potential of mitochondrial inner membrane (Peng et al, 2022;Campos et al, 2023).…”

Section: Ir2 Combined With Flc Inhibit the Hyphal Formation Of C Albi...mentioning

confidence: 99%

Cyclometalated iridium(III) complexes combined with fluconazole: antifungal activity against resistant C. albicans

Zhu

et al. 2023

Front. Cell. Infect. Microbiol.

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Candida albicans (C. albicans) is a ubiquitous clinical fungal pathogen. In recent years, combination therapy, a potential treatment method to overcome C. albicans resistance, has gained traction. In this study, we synthesized a series of cyclometalated iridium(III) complexes with the formula [Ir(C-N)2(tpphz)](PF6) (C-N = 2-phenylpyridine (ppy, in Ir1), 2-(2-thienyl)pyridine (thpy, in Ir2), 2-(2,4-difluorophenyl) pyridine (dfppy, in Ir3), tpphz = tetrapyrido[3,2-a:2',3'-c:3'',2''-h:2''',3'''-j]phenazine) and polypyridyl ruthenium(II) complexes with the formula [Ru(N-N)2(tpphz)](PF6)2 (N-N = 2,2'-bipyridine (bpy, in Ru1), 1,10-phenanthroline (phen, in Ru2), 4,7-diphenyl-1,10-phenanthroline (DIP, in Ru3)), and investigated their antifungal activities against drug-resistant C. albicans and their combination with fluconazole (FLC). Of which, the combination of the lead iridium(III) complex Ir2 and FLC showed strong antifungal activity against drug-resistant C. albicans. Mechanism studies have shown that they can inhibit the formation of hyphae and biofilm, damage mitochondrial function and accumulate intracellular ROS. Therefore, iridium(III) complexes combined with FLC can be used as a promising treatment to exert anti-drug-resistant C. albicans activity, in order to improve the treatment efficiency of fungal infection.

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“…Isobaric tags for relative and absolute quantitation (iTRAQ), which is based on the enzymatic digestion of proteins prior to isobaric labeling. iTRAQ is a superior choice in quantitative proteomics due to their high proteome coverage and labeling efficiency, and has been applied to various academic fields in the latest years [13][14][15]. In the present study, we investigated the biological functions of the differentially abundant proteins between white skin (WS) and black skin (BS) of sheep by using iTRAQ to unravel the mechanism of coat color.…”

Section: Introductionmentioning

confidence: 99%

Skin proteomic screening and functional analysis of differential proteins associated with coat color in sheep (Ovis aries)

Yin,

Hao,

Zhao

et al. 2024

Anim Biosci

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Objective: Coat color is an important characteristic and economic trait in domestic sheep. In this study, we explored the potential mechanisms and the signaling pathways involved in coat color regulation for sheep. Methods: Isobaric tags for relative and absolute quantification (iTRAQ) technology was used to catalog global protein expression profiles in skin of sheep with black versus white coat color. Immunofluorescence was used to observe the expression localization of differential protein. Western blot and quantitative real time polymerase chain reaction (qRT-PCR) were used to evaluate their role in the coat color formation of sheep. Results: A total of 136 differential proteins were obtained in different coat colors, including 101 up-regulated and 35 down-regulated. Pigmentation function entries were enriched through GO annotation. Tyrosine metabolism and platelet activation signaling pathway were extracted by KEGG analysis. APOA1 (Apolipoprotein A-1)and FGA (Fibrinogen alpha chain) were found to be critical differential proteins by the interaction of differential proteins in the direct-interaction network diagram.Strikingly, twenty candidate differential proteins were screened, from which ACTB (Beta-actin) protein showed higher expression in white sheep skin, while ALB (albumin), APOA1 MAOA (Amine oxidase) and FGA proteins showed higher expression in black sheep skin, which validated by immunofluorescence, western blot and qRT-PCR. Conclusion:Our studies identified several novel proteins that may involved in A c c e p t e d A r t i c l e the coat color formation of sheep. The white and black sheep skin proteome profiles obtained provide a valuable resource for future research to understand the network of protein expression controlling skin physiology and melanogenesis in sheep.

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iTRAQ-based proteomics revealed baicalein enhanced oxidative stress of Candida albicans by upregulating CPD2 expression

Cited by 4 publications

References 38 publications

Exploration of Baicalein-Core Derivatives as Potent Antifungal Agents: SAR and Mechanism Insights

Exploration of Baicalein-Core Derivatives as Potent Antifungal Agents: SAR and Mechanism Insights

Cyclometalated iridium(III) complexes combined with fluconazole: antifungal activity against resistant C. albicans

Skin proteomic screening and functional analysis of differential proteins associated with coat color in sheep (Ovis aries)

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