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Molecules. 2018 Nov 22;23(12). pii: E3058. doi: 10.3390/molecules23123058.

On the Mechanism of Action of Anti-Inflammatory Activity of Hypericin: An In Silico Study Pointing to the Relevance of Janus Kinases Inhibition.

Author information

1
Department of Food and Drug, University of Parma, Area Parco delle Scienze 27/A, 43124 Parma, Italy. luca.dellafiora@unipr.it.
2
Department of Food and Drug, University of Parma, Area Parco delle Scienze 27/A, 43124 Parma, Italy. gianni.galaverna@unipr.it.
3
Department of Chemistry, Biology and Biotechnology, University of Perugia, via Elce di Sotto, 8, 06123 Perugia, Italy. gabri@chemiome.chm.unipg.it.
4
Department of Food and Drug, University of Parma, Area Parco delle Scienze 27/A, 43124 Parma, Italy. chiara.dallasta@unipr.it.
5
Department of Food and Drug, University of Parma, Area Parco delle Scienze 27/A, 43124 Parma, Italy. renato.bruni@unipr.it.

Abstract

St. John's Wort (Hypericum perforatum L.) flowers are commonly used in ethnomedical preparations with promising outcomes to treat inflammation both per os and by topical application. However, the underlying molecular mechanisms need to be described toward a rational, evidence-based, and reproducible use. For this purpose, the aptitude of the prominent Hypericum metabolite hypericin was assessed, along with that of its main congeners, to behave as an inhibitor of janus kinase 1, a relevant enzyme in inflammatory response. It was used a molecular modeling approach relying on docking simulations, pharmacophoric modeling, and molecular dynamics to estimate the capability of molecules to interact and persist within the enzyme pocket. Our results highlighted the capability of hypericin, and some of its analogues and metabolites, to behave as ATP-competitive inhibitor providing: (i) a likely mechanistic elucidation of anti-inflammatory activity of H. perforatum extracts containing hypericin and related compounds; and (ii) a rational-based prioritization of H. perforatum components to further characterize their actual effectiveness as anti-inflammatory agents.

KEYWORDS:

Hypericum perforatum; anti-inflammatory activity; hypericin; hypericin metabolites; in silico pharmacodynamics; janus kinase 1

PMID:
30467287
DOI:
10.3390/molecules23123058
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