Plant-derived isoquinoline alkaloids that target ergosterol biosynthesis discovered by using a novel antifungal screening tool

Wong-Deyrup, Siu Wah; Song, Xun; Ng, Tsz Wai; Liu, Xiu Bin; Zeng, Jian; Qing, Zhi Xing; Deyrup, Stephen T.; He, Zhen Dan; Zhang, Hongjie

doi:10.1016/j.biopha.2021.111348

Cited by 14 publications

(13 citation statements)

References 45 publications

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“…Despite our observation that the total lipid content of the antofine‐treated Pdw03 mycelia drastically decreased, the ergosterol content remained unaffected. This totally contradicts findings of many previous studies that emphasize the role of ergosterol in the antifungal damage of fungal cell membranes, including our previous the IMZ‐sensitive Pds01 (Wong‐Deyrup et al., 2021; Xin et al., 2019). Instead, an overproduction of ROS and increase in intracellular MDA content was recorded following treatment of Pdw03 with antofine, implying that antofine induced oxidative stress within the Pdw03 cells, leading to lipid peroxidation.…”

Section: Discussioncontrasting

confidence: 99%

Antofine inhibits postharvest green mold due to imazalil‐resistant Penicillium digitatum strain Pdw03 by triggering oxidative burst

Xin

Reymick

et al. 2021

J. Food Biochem.

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Section: Discussioncontrasting

confidence: 99%

Antofine inhibits postharvest green mold due to imazalil‐resistant Penicillium digitatum strain Pdw03 by triggering oxidative burst

Xin

Reymick

et al. 2021

J. Food Biochem.

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“…In this study, four alkaloid active compounds, SAN, CHE, ALL, and PRO, were screened based on previous studies, which have shown the compounds to have good antibacterial and anti-inflammatory pharmacological effects [34][35][36]. When screening for ADME, it is generally accepted that compounds with a molecular weight greater than 600 are difficult to be absorbed through the skin; and the more water-soluble the substance, the more difficult it is to pass through the skin (Log P < 0); strongly lipophilic substances (Log P > 3) can easily pass through the skin barrier but are difficult to be absorbed when they enter the body, and small molecules can penetrate through the skin and are well absorbed when the water−oil partition coefficient is between 0 and 3.…”

Section: Discussionmentioning

confidence: 99%

Integrating Network Pharmacology and Molecular Docking to Analyse the Potential Mechanism of action of Macleaya cordata (Willd.) R. Br. in the Treatment of Bovine Hoof Disease

Dong

Liu

Zou

et al. 2021

Veterinary Sciences

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Based on network pharmacological analysis and molecular docking techniques, the main components of M. cordata for the treatment of bovine relevant active compounds in M. cordata were searched for through previous research bases and literature databases, and then screened to identify candidate compounds based on physicochemical properties, pharmacokinetic parameters, bioavailability, and drug-like criteria. Target genes associated with hoof disease were obtained from the GeneCards database. Compound−target, compound−target−pathway−disease visualization networks, and protein−protein interaction (PPI) networks were constructed by Cytoscape. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed in R language. Molecular docking analysis was done using AutoDockTools. The visual network analysis showed that four active compounds, sanguinarine, chelerythrine, allocryptopine and protopine, were associated with the 10 target genes/proteins (SRC, MAPK3, MTOR, ESR1, PIK3CA, BCL2L1, JAK2, GSK3B, MAPK1, and AR) obtained from the screen. The enrichment analysis indicated that the cAMP, PI3K-Akt, and ErbB signaling pathways may be key signaling pathways in network pharmacology. The molecular docking results showed that sanguinarine, chelerythrine, allocryptopine, and protopine bound well to MAPK3 and JAK2. A comprehensive bioinformatics-based network topology strategy and molecular docking study has elucidated the multi-component synergistic mechanism of action of M. cordata in the treatment of bovine hoof disease, offering the possibility of developing M. cordata as a new source of drugs for hoof disease treatment.

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“…After 48 h of incubation, the cells were harvested and washed with PBS. Cell total sterol was extracted and measured by high-performance liquid chromatography (HPLC) as previously described (Wong-Deyrup et al, 2021 ).…”

Section: Methodsmentioning

confidence: 99%

“…of SAN for 10 consecutive days. Given the diverse activities of SAN (Alcantara et al, 2005 ; Gaziano et al, 2016 ; Wong-Deyrup et al, 2021 ), together with the safe daily oral dose of SAN of 5 mg/kg b.w. (Kosina et al, 2004 ), this compound is still worthy of study.…”

Section: Introductionmentioning

confidence: 99%

Sanguinarine, Isolated From Macleaya cordata, Exhibits Potent Antifungal Efficacy Against Candida albicans Through Inhibiting Ergosterol Synthesis

Hu²,

Hu³

et al. 2022

Front. Microbiol.

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In recent decades, infections caused by the opportunistic fungus Candida albicans have increased, especially in patients with immunodeficiency. In this study, we investigated the mechanism of action of sanguinarine (SAN) against C. albicans both in vitro and in vivo. SAN exhibited antifungal activity against C. albicans clinical isolates, with MICs in the range of 112.8–150.5 μM. Furthermore, scanning electron and transmission electron microscopy showed that SAN induced morphological changes as well as structure disruption in C. albicans cells, including masses of cellular debris, ruptured cell walls, and membrane deformation. Flow cytometry revealed that SAN could lead to cell membrane damage, and ergosterol content analysis indicated that SAN could cause ergosterol content reduction exceeding 90%. Further, we validated the efficacy of SAN against candidiasis caused by C. albicans in a murine model, and SAN significantly improved survival and reduced weight loss compared to vehicle. The treatment of 1.5 and 2.5 mg/kg/d SAN obviously reduced the fungal burden in the kidney. In addition, histopathological examination indicated that no fungal cells were observed in lung and kidney tissues after SAN treatment. Hence, this study suggests that SAN is a promising plant-derived compound for the development of an effective anticandidal agent.

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Plant-derived isoquinoline alkaloids that target ergosterol biosynthesis discovered by using a novel antifungal screening tool

Cited by 14 publications

References 45 publications

Antofine inhibits postharvest green mold due to imazalil‐resistant Penicillium digitatum strain Pdw03 by triggering oxidative burst

Antofine inhibits postharvest green mold due to imazalil‐resistant Penicillium digitatum strain Pdw03 by triggering oxidative burst

Integrating Network Pharmacology and Molecular Docking to Analyse the Potential Mechanism of action of Macleaya cordata (Willd.) R. Br. in the Treatment of Bovine Hoof Disease

Sanguinarine, Isolated From Macleaya cordata, Exhibits Potent Antifungal Efficacy Against Candida albicans Through Inhibiting Ergosterol Synthesis

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