Natural products from traditional medicine as promising agents targeting at different stages of oral biofilm development

Chi, Yaqi; Wang, Ye; Ji, Mengzhen; Li, Yanyao; Hua, Zhu; Yan, Yujia; Fu, Di; Zou, Ling; Ren, Baiping

doi:10.3389/fmicb.2022.955459

Cited by 8 publications

(5 citation statements)

References 169 publications

(183 reference statements)

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“… 55 , 57 Traditional Chinese Medicines (TCMs) are efficacious resources for the development of anti-virulence drugs due to its abundant structures, low toxicities, multiple bioactivities. 58 , 59 …”

Section: Introductionmentioning

confidence: 99%

Artemisinins inhibit oral candidiasis caused by Candida albicans through the repression on its hyphal development

Liang,

Chen,

Wang

et al. 2023

Int J Oral Sci

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Candida albicans is the most abundant fungal species in oral cavity. As a smart opportunistic pathogen, it increases the virulence by switching its forms from yeasts to hyphae and becomes the major pathogenic agent for oral candidiasis. However, the overuse of current clinical antifungals and lack of new types of drugs highlight the challenges in the antifungal treatments because of the drug resistance and side effects. Anti-virulence strategy is proved as a practical way to develop new types of anti-infective drugs. Here, seven artemisinins, including artemisinin, dihydroartemisinin, artemisinic acid, dihydroartemisinic acid, artesunate, artemether and arteether, were employed to target at the hyphal development, the most important virulence factor of C. albicans. Artemisinins failed to affect the growth, but significantly inhibited the hyphal development of C. albicans, including the clinical azole resistant isolates, and reduced their damage to oral epithelial cells, while arteether showed the strongest activities. The transcriptome suggested that arteether could affect the energy metabolism of C. albicans. Seven artemisinins were then proved to significantly inhibit the productions of ATP and cAMP, while reduced the hyphal inhibition on RAS1 overexpression strain indicating that artemisinins regulated the Ras1-cAMP-Efg1 pathway to inhibit the hyphal development. Importantly, arteether significantly inhibited the fungal burden and infections with no systemic toxicity in the murine oropharyngeal candidiasis models in vivo caused by both fluconazole sensitive and resistant strains. Our results for the first time indicated that artemisinins can be potential antifungal compounds against C. albicans infections by targeting at its hyphal development.

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Section: Introductionmentioning

confidence: 99%

Artemisinins inhibit oral candidiasis caused by Candida albicans through the repression on its hyphal development

Liang,

Chen,

Wang

et al. 2023

Int J Oral Sci

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“…The reduction of gtfB and gtfC genes which encode for the major enzymes involved in EPS production ( Koo et al, 2010 ), may contribute to the reduced biofilm formation caused by AA. This assumption is based on findings that have shown a link between gtf gene expression and biofilm formation in S. mutans ( He et al, 2019 ; Schneider-Rayman et al, 2021 ; Chi et al, 2022 ; Zheng et al, 2023 ). However, we cannot exclude the possibility that other mechanisms are also involved in the anti-biofilm activity of AA.…”

Section: Discussionmentioning

confidence: 99%

Anti-bacterial and anti-biofilm activities of arachidonic acid against the cariogenic bacterium Streptococcus mutans

Chamlagain,

Hu,

Sionov

et al. 2024

Front. Microbiol.

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Streptococcus mutans is a Gram-positive, facultative anaerobic bacterium, which causes dental caries after forming biofilms on the tooth surface while producing organic acids that demineralize enamel and dentin. We observed that the polyunsaturated arachidonic acid (AA) (ω-6; 20:4) had an anti-bacterial activity against S. mutans, which prompted us to investigate its mechanism of action. The minimum inhibitory concentration (MIC) of AA on S. mutans was 25 μg/ml in the presence of 5% CO2, while it was reduced to 6.25–12.5 μg/ml in the absence of CO2 supplementation. The anti-bacterial action was due to a combination of bactericidal and bacteriostatic effects. The minimum biofilm inhibitory concentration (MBIC) was the same as the MIC, suggesting that part of the anti-biofilm effect was due to the anti-bacterial activity. Gene expression studies showed decreased expression of biofilm-related genes, suggesting that AA also has a specific anti-biofilm effect. Flow cytometric analyses using potentiometric DiOC2(3) dye, fluorescent efflux pump substrates, and live/dead SYTO 9/propidium iodide staining showed that AA leads to immediate membrane hyperpolarization, altered membrane transport and efflux pump activities, and increased membrane permeability with subsequent membrane perforation. High-resolution scanning electron microscopy (HR-SEM) showed remnants of burst bacteria. Furthermore, flow cytometric analysis using the redox probe 2′,7′-dichlorofluorescein diacetate (DCFHDA) showed that AA acts as an antioxidant in a dose-dependent manner. α-Tocopherol, an antioxidant that terminates the radical chain, counteracted the anti-bacterial activity of AA, suggesting that oxidation of AA in bacteria leads to the production of cytotoxic radicals that contribute to bacterial growth arrest and death. Importantly, AA was not toxic to normal Vero epithelial cells even at 100 μg/ml, and it did not cause hemolysis of erythrocytes. In conclusion, our study shows that AA is a potentially safe drug that can be used to reduce the bacterial burden of cariogenic S. mutans.

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“…Natural products are considered as promising candidates for developing new drugs due to their multiple activities and biological safety (Chi et al, 2022;Newman et al, 2016). Sea cucumbers is popular as a functional food around the world and tonic for thousands of years because it is rich in natural bioactive components, such as anticancer and antimicrobial compounds (Bordbar et al, 2011;Dai et al, 2020).…”

Section: Altmentioning

confidence: 99%

Holotoxin A1 from Apostichopus japonicus inhibited oropharyngeal and intra-abdominal candidiasis by inducing of oxidative damage in Candida albicans

Liao

Xia

Meng

et al. 2023

Preprint

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Background and Purpose: The holotoxin A1, isolated from Apostichopus japonicus, has shown potent antifungal activities with unclear mechanism and efficacy against candidiasis. This study aimed to reveal the antifungal effects and mechanism of holotoxin A1 against Candida albicans in vitro and in candidiasis murine models for the first time. Experimental Approach: The antifungal effect of holotoxin A1 against C. albicans was tested in vitro. To explore the antifungal mechanism of holotoxin A1, the transcriptome, ROS levels, and mitochondrial function of C. albicans was evaluated. The oropharyngeal and intra-abdominal candidiasis mouse models were used to verify the effectiveness and systematic toxicity in vivo. Key Results: Holotoxin A1 was a potent fungicide against C. albicans SC5314, clinical strains and drug-resistant strains. Holotoxin A1 inhibited the oxidative phosphorylation and induced oxidative damage by increasing intracellular accumulation of ROS in C. albicans. Holotoxin A1 caused the disfunction of mitochondria by depolarizing the mitochondrial membrane potential and reducing the production of ATP. Holotoxin A1 directly inhibited the enzymatic activity of mitochondrial complex I (CI) and antagonized with the rotenone, an inhibitor of CI, against C. albicans. Meanwhile, the CI subunit NDH51 null mutants showed the decreased susceptibility to holotoxin A1. Furthermore, holotoxin A1 significantly reduced fungal burden and infections with no significant systemic toxicity in oropharyngeal and intra-abdominal candidiasis murine models. Conclusions and Implications: Holotoxin A1 was a promising candidate for the development of novel antifungal drug against both oropharyngeal and intra-abdominal candidiasis, especially caused by the drug resistant strains.

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Natural products from traditional medicine as promising agents targeting at different stages of oral biofilm development

Cited by 8 publications

References 169 publications

Artemisinins inhibit oral candidiasis caused by Candida albicans through the repression on its hyphal development

Artemisinins inhibit oral candidiasis caused by Candida albicans through the repression on its hyphal development

Anti-bacterial and anti-biofilm activities of arachidonic acid against the cariogenic bacterium Streptococcus mutans

Holotoxin A1 from Apostichopus japonicus inhibited oropharyngeal and intra-abdominal candidiasis by inducing of oxidative damage in Candida albicans

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