ReferenceID 5332

Uncovering the efficacy and mechanisms of Genkwa flos and bioactive ingredient genkwanin against L. monocytogenes infection

J Ethnopharmacol

Ethnopharmacological relevance: Genkwa flos (yuanhua in Chinese), the dried flower buds of the plant Daphne genkwa Siebold & Zucc., as a traditional herb widely used for the treatment of inflammation-related symptoms and

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Reference Id
5332
Evidence Id
21922
Core Evidence Id
21922
Source Reference Id
3918
Herb2 Reference Id
HBREF004715
Subject Paper Key
HBIN027475_35870686
Pubmed Id
35870686
Doi
10.1016/j.jep.2022.115571
Paper Title
Uncovering the efficacy and mechanisms of Genkwa flos and bioactive ingredient genkwanin against L. monocytogenes infection
Paper Abstract
Ethnopharmacological relevance: Genkwa flos (yuanhua in Chinese), the dried flower buds of the plant Daphne genkwa Siebold & Zucc., as a traditional herb widely used for the treatment of inflammation-related symptoms and diseases, with the efficacies of diuretic, phlegm-resolving and cough suppressant. Aim of the study: Traditional Chinese Medicine (TCM) is presumed to be of immense potential against pathogens infection. Whereas, the potential efficacy and mechanisms of Genkwa flos against L. monocytogenes infection has not been extensively explored. The present study aimed to identify the bioactive ingredients of Genkwa flos against L. monocytogenes infection and to delineate the underlying mechanisms of action. Materials and methods: Bioinformatics approach at protein network level was employed to investigate the therapeutic mechanisms of Genkwa flos against L. monocytogenes infection. And hemolysis inhibition assay, cytoprotection test, western blotting, oligomerization assay and molecular docking analysis were applied to substantiate the multiple efficacies of Genkwa flos and the bioactive ingredient genkwanin. Histopathological analysis and biochemistry detection were conducted to evaluate the in vivo protective effect of genkwanin. Results: Network pharmacology and experimental validation revealed that Traditional Chinese Medicine (TCM) Genkwa flos exhibited anti-L. monocytogenes potency and was found to inhibit the hemolytic activity of LLO. Bioactive ingredient genkwanin interfered with the pore-forming activity of LLO by engaging the active residues Tyr414, Tyr98, Asn473, Val100, Tyr440 and Val438, and thereby attenuated LLO-mediated cytotoxicity. Consistent with the bioinformatics prediction, exposed to genkwanin could upregulate the Nrf2 level and promote the translocation of Nrf2. In vivo, genkwanin oral administration (80 mg/kg) significantly protected against systemic L. monocytogenes infection, as evidenced by reduced myeloperoxidase (MPO) and malondialdehyde (MDA) levels, increased mice survival rate by 30% and decreased pathogen colonization. Conclusion: Our study demonstrated that Genkwa flos is a potential anti-L. monocytogenes TCM, highlighted the therapeutic potential of Genkwa flos active ingredient genkwanin by targeting the pore-forming cytolysin LLO and acting as a promising antioxidative candidate against L. monocytogenes infection.
Journal
J Ethnopharmacol
Publish Year
2022
Experiment Subject
mouse
Experiment Type
Cell Experiment
Phenotype Related
Inflammation
Paper Title Cn
Paper Title En
Uncovering the efficacy and mechanisms of Genkwa flos and bioactive ingredient genkwanin against L. monocytogenes infection
Bilingual Status
semi_complete