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Berberine hydrochloride (BH), an active component of Coptis chinensis and other plant taxa, has broad antimicrobial activity and may be useful for the treatment of Candida infections. In this study, the mechanisms underlying the inhibitory effect of BH against Candida albicans were evaluated, with a focus on the high-osmolarity glycerol mitogen-activated protein kinase (HOG-MAPK) pathway, which regulates multiple physiological functions. BH (256 and 64 μg ml-1) significantly increased intracellular glycerol and ROS levels in C. albicans, inhibited germ tube and hyphal formation, and increased chitin and β-1,3-glucan exposure on the cell wall. The inhibitory effect of BH was positively correlated with its concentration, and the inhibitory effect of 256 μg ml-1 BH was greater than that of 4 μg ml-1 fluconazole (FLC). Furthermore, RT-PCR analysis showed that 256 and 64 μg ml-1 BH altered the HOG-MAPK pathway in C. albicans. In particular, the upregulation of the core genes, SLN1, SSK2, HOG1, and PBS2 may affect the expression of key downstream factors related to glycerol synthesis and osmotic pressure (GPD1), ROS accumulation (ATP11 and SOD2), germ tube and hyphal formation (HWP1), and cell wall integrity (CHS3 and GSC1). BH affects multiple biological processes in C. albicans; thus, it can be an effective alternative to conventional azole antifungal agents.

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.

Berberine hydrochloride (BH), an active component of Coptis chinensis and other plant taxa, has broad antimicrobial activity and may be useful for the treatment of Candida infections. In this study, the mechanisms underlying the inhibitory effect of BH against Candida albicans were evaluated, with a focus on the high-osmolarity glycerol mitogen-activated protein kinase (HOG-MAPK) pathway, which regulates multiple physiological functions. BH (256 and 64 μg ml

Background: Staphylococcus epidermidis causes prosthetic valve endocarditis, urinary tract infection, and implant-related infections. These are difficult to treat often due to drug resistance, particularly because S. epidermidis biofilms are inherently resistant to most antibiotics. Salvia miltiorrhiza is a kind of sichuan-specific medicinal herb, and has effective ingredients, such as cryptotanshinone. Cryptotanshinone was demonstrated to have anti-microbial properties and no resistance. Objectives: The current study investigated the effects of cryptotanshinone on S. epidermidis biofilm formation, and found new agents controlling S. epidermidis biofilm formation and resistance caused by biofilm. Methods: The effects were further analyzed by crystal violet assay (CV), 2, 3-bis [2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide inner salt assay (XTT), and scanning electron microscopy (SEM). The qRT-PCR assay was used to determine the expressions of biofilm key genes, including icaA, atlE, aap and luxS. Results: The amount treated by cryptotanshinone was reduced compared with the non-treating group, so did the metabolic activity inside the biofilm. Even the micro-structure was destroyed with cryptotanshinone. The expressions of biofilm key genes, including icaA, atlE, aap, and luxS, were down-regulated by cryptotanshinone. Conclusions: There is new insight that cryptotanshinone could inhibit immature biofilms and the down-regulations of icaA, atlE, aap, and luxS might explain this inhibitory effect.