Integrated serum metabolomics and network pharmacology approach to reveal the potential mechanisms of withanolides from the leaves of Datura metel L. on psoriasis.
Angiogenesis Inducing Agents
/ pharmacology
Animals
Anti-Inflammatory Agents, Non-Steroidal
/ pharmacology
Blotting, Western
Chromatography, High Pressure Liquid
Cytokines
/ drug effects
Datura metel
/ chemistry
Enzyme-Linked Immunosorbent Assay
Hypoxia-Inducible Factor 1, alpha Subunit
/ antagonists & inhibitors
Male
Mass Spectrometry
Metabolomics
Mice
Mice, Inbred C57BL
Plant Leaves
/ chemistry
Psoriasis
/ drug therapy
Signal Transduction
/ drug effects
Skin
/ pathology
Vascular Endothelial Growth Factor A
/ antagonists & inhibitors
Withanolides
/ blood
Datura metel L.
Metabolomics
Network pharmacology
Psoriasis
Withanolides
Journal
Journal of pharmaceutical and biomedical analysis
ISSN: 1873-264X
Titre abrégé: J Pharm Biomed Anal
Pays: England
ID NLM: 8309336
Informations de publication
Date de publication:
15 Jul 2020
15 Jul 2020
Historique:
received:
30
11
2019
revised:
07
03
2020
accepted:
22
03
2020
pubmed:
18
4
2020
medline:
30
3
2021
entrez:
18
4
2020
Statut:
ppublish
Résumé
Psoriasis is a chronic, immune-mediated inflammatory skin disease and highly depends on inflammation and angiogenesis as well as other pathways. Our previous study showed that the withanolides from the leaves of Datura metel L. exhibited significant therapeutically effect on psoriasis, but the mechanisms concerning this effect have not been systematically studied. The purpose of this paper was to investigate the possible mechanism of withanolides for treating psoriasis using an integrated metabolomics and network pharmacology strategy. Untargeted metabolomics profiling of serum with UHPLC/Orbitrap MS and a multivariate data method were performed to discover the potential biomarkers and metabolic pathways. Afterward, the compound-target-pathway network of withanolides for psoriasis was constructed by virtue of network pharmacology. Finally, the crucial pathways were selected by integrating the results of metabolomics and network pharmacology, and then validated by ELISA and western blot analysis. The results showed that withanolides could exert excellent effects on psoriasis through regulating two types of pathways, angiogenesis and inflammation, including sphingolipids metabolism and HIF-1α/VEGF pathway, reflected by inhibiting the production of inflammatory cytokines (IL-1β, IL-6, IL-8, IFN-γ, TNF-α, HIF-1α and VEGF), as well as reducing the protein expressions of HIF-1α and VEGF. Our study successfully explained the polypharmcological mechanisms underlying the efficiency of withanolides from the D. metel L. leaves on treating psoriasis. Meanwhile, it was also valuable for performing a systematical investigation of herb medicines, as well as for efficiently predicting the therapeutic mechanisms of traditional Chinese medicine.
Identifiants
pubmed: 32302925
pii: S0731-7085(19)32916-4
doi: 10.1016/j.jpba.2020.113277
pii:
doi:
Substances chimiques
Angiogenesis Inducing Agents
0
Anti-Inflammatory Agents, Non-Steroidal
0
Cytokines
0
Hif1a protein, mouse
0
Hypoxia-Inducible Factor 1, alpha Subunit
0
Vascular Endothelial Growth Factor A
0
Withanolides
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
113277Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare no competing financial interest.