Synergistic Effect of Berberine Hydrochloride and Fluconazole Against Candida albicans Resistant Isolates

Yong, Jiangyan; Zu, Ruiling; Huang, Xiaoxue; Ge, Yiman; Li, Yan

doi:10.3389/fmicb.2020.01498

Cited by 30 publications

(16 citation statements)

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“…The MIC of KBN against planktonic C. albicans was 6.25 mg/mL, for all the tested strains ( Table 3 ). The dynamic antifungal effect of the drug could be monitored by the time-kill curve assays for CMSS(F) 98001 and 901 strains ( Yong et al, 2020 ). The results showed that KBN appeared to exhibit strong antifungal activity against C. albicans .…”

Section: Resultsmentioning

confidence: 99%

“…To further test the minimal inhibitory concentration (MIC) of FLC-resistant C. albicans , the final concentration ranged from 4 to 2,048 μg/mL for FLC. Plates were incubated at 35°C for 48 h. MIC endpoints were read as previously described ( Li et al, 2019 ; Yan et al, 2019 ; Yong et al, 2020 ). In brief, the MIC was determined as the lowest concentration of the drug that inhibited planktonic C. albicans growth by 80% compared with that of the drug-free C. albicans .…”

Section: Methodsmentioning

confidence: 99%

“…To further study the antifungal activity of KBN, a time-kill curve assay was performed as described previously ( Yong et al, 2020 ). Time-kill experiments were conducted in RPMI 1640 medium with MOPS.…”

Section: Methodsmentioning

confidence: 99%

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Kangbainian Lotion Ameliorates Vulvovaginal Candidiasis in Mice by Inhibiting the Growth of Fluconazole-Resistant Candida albicans and the Dectin-1 Signaling Pathway Activation

et al. 2022

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Vulvovaginal candidiasis (VVC) is an infectious disease caused by Candida species, which affects millions of women worldwide every year. The resistance to available antifungal drugs for clinical treatment is a growing problem. The treatment of refractory VVC caused by azole-resistant Candida is still facing challenges. However, research on new antifungal drugs is progressing slowly. Although a lot of reports on new antifungal drugs, only three new antifungal drugs (Isavuconazole, ibrexafungerp, and rezafungin) and two new formulations of posaconazole were marketed over the last decade. Chinese botanical medicine has advantages in the treatment of drug-resistant VVC, such as outstanding curative effects and low adverse reactions, which can improve patients’ comfort and adherence to therapy. Kangbainian lotion (KBN), a Chinese botanical formulation, has achieved very good clinical effects in the treatment of VVC. In this study, we investigated the antifungal and anti-inflammatory effects of KBN at different doses in fluconazole-resistant (FLC-resistant) VVC model mice. We further studied the antifungal mechanism of KBN against FLC-resistant Candida albicans (C. albicans) and the anti-inflammatory mechanism correlated with the Dectin-1 signaling pathway. In vivo and in vitro results showed that KBN had strong antifungal and anti-inflammatory effects in FLC-resistant VVC, such as inhibiting the growth of C. albicans and vaginal inflammation. Further studies showed that KBN inhibited the biofilm and hypha formation, reduced adhesion, inhibited ergosterol synthesis and the expression of ergosterol synthesis-related genes ERG11, and reduced the expression of drug-resistant efflux pump genes MDR1 and CDR2 of FLC-resistant C. albicans in vitro. In addition, in vivo results showed that KBN reduced the expression of inflammatory factor proteins TNF-α, IL-1β, and IL-6 in vaginal tissues, and inhibited the expression of proteins related to the Dectin-1 signaling pathway. In conclusion, our study revealed that KBN could ameliorate vaginal inflammation in VVC mice caused by FLC-resistance C. albicans. This effect may be related to inhibiting the growth of FLC-resistance C. albicans and dectin-1 signaling pathway activation.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Kangbainian Lotion Ameliorates Vulvovaginal Candidiasis in Mice by Inhibiting the Growth of Fluconazole-Resistant Candida albicans and the Dectin-1 Signaling Pathway Activation

et al. 2022

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“…Another flavonoid, kaempferol, could downregulate CDR1 and CDR2 genes in fluconazole-resistant C. albicans [ 99 ]. Berberine hydrochloride, traditional Chinese medicine with antimicrobial effects, reduces intracellular efflux of fluconazole by downregulating CDR1 [ 100 ], while polyunsaturated fatty acids could reduce efflux from C. krusei cells [ 101 ]. Benzoxazole derivatives could interfere with both cell efflux and ergosterol synthesis in C. albicans [ 62 ].…”

Section: Recent Update On Antifungal Targets and Strategiesmentioning

confidence: 99%

Emerging Antifungal Targets and Strategies

Ivanov

Ćirić

Stojković

2022

IJMS

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Despite abundant research in the field of antifungal drug discovery, fungal infections remain a significant healthcare burden. There is an emerging need for the development of novel antifungals since those currently available are limited and do not completely provide safe and secure protection. Since the current knowledge regarding the physiology of fungal cells and the infection mechanisms is greater than ever, we have the opportunity to use this for the development of novel generations of antifungals. In this review, we selected and summarized recent studies describing agents employing different antifungal mechanisms. These mechanisms include interference with fungal resistance, including impact on the efflux pumps and heat shock protein 90. Additionally, interference with virulence factors, such as biofilms and hyphae; the impact on fungal enzymes, metabolism, mitochondria, and cell wall; and antifungal vaccines are explored. The agents investigated belong to different classes of natural or synthetic molecules with significant attention given also to plant extracts. The efficacy of these antifungals has been studied mainly in vitro with some in vivo, and clinical studies are needed. Nevertheless, there is a large quantity of products employing novel antifungal mechanisms that can be further explored for the development of new generation of antifungals.

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“…We previously assessed the effects of BH on drug transporters and intracellular calcium homeostasis [21], and observed that BH can inhibit the growth of fluconazole-resistant C. albicans . We subsequently found that drug-resistant C. albicans was more sensitive to fluconazole after BH treatment.…”

Section: Introductionmentioning

confidence: 99%

Antifungal activity and potential mechanism of berberine hydrochloride against fluconazole-resistant Candida albicans

Huang

Zheng

Yong

et al. 2022

Journal of Medical Microbiology

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Introduction. The emergence of resistance to fluconazole in Candida albicans has made the clinical treatment of this microbe difficult. A potential strategy to address this problem involves diminishing fungal resistance to antimicrobial drugs. Hypothesis. Berberine hydrochloride (BH), the primary active ingredient of the traditional Chinese medicine (TCM) Coptis, inhibits the growth of fluconazole-resistant C. albicans through its action on the high-osmolarity glycerol mitogen-activated protein kinase (HOG-MAPK) pathway. Aim. To examine the effect of BH on the HOG-MAPK pathway to assess the potential molecular mechanism by which BH inhibits fluconazole-resistant C. albicans. Methodology. The minimum inhibitory concentration (MIC) of BH to fluconazole-resistant C. albicans was measured using the broth microdilution approach to determine the concentration of effective drug intervention. Changes in physiological functions regulated by the HOG-MAPK pathway in response to BH treatment were measured, as well as the expression of central signalling pathway genes and key downstream factors by qRT-PCR and Western blotting, respectively. Results. BH inhibited fluconazole-resistant C. albicans and the sensitivity to fluconazole increased after BH treatment. At a concentration of 256 and 64 μg ml−1 BH may affect key downstream factors that regulate several physiological functions of C. albicans by upregulating the core genes expression of SLN1, SSK2, HOG1, and PBS2 in the HOG-MAPK pathway. Upregulation of GPD1, the key gene for glycerol synthesis, increased cell osmotic pressure. BH treatment increased the accumulation of reactive oxygen species by upregulating the expression of the key respiratory metabolism gene ATP11 and downregulating the expression of the superoxide dismutase gene SOD2. Furthermore, downregulation of mycelial-specific HWP1 hindered the morphological transformation of C. albicans and inhibition of the chitin synthase gene CHS3 and the β-(1,3) glucan synthase gene GSC1 impaired cytoderm integrity. Conclusion. BH affects multiple target genes in diminishing the resistance of C. albicans strains to fluconazole. This effect may be related to the action of BH on the HOG-MAPK pathway.

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Synergistic Effect of Berberine Hydrochloride and Fluconazole Against Candida albicans Resistant Isolates

Cited by 30 publications

References 58 publications

Kangbainian Lotion Ameliorates Vulvovaginal Candidiasis in Mice by Inhibiting the Growth of Fluconazole-Resistant Candida albicans and the Dectin-1 Signaling Pathway Activation

Kangbainian Lotion Ameliorates Vulvovaginal Candidiasis in Mice by Inhibiting the Growth of Fluconazole-Resistant Candida albicans and the Dectin-1 Signaling Pathway Activation

Emerging Antifungal Targets and Strategies

Antifungal activity and potential mechanism of berberine hydrochloride against fluconazole-resistant Candida albicans

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