Immunomodulatory of sesquiterpenoids and sesquiterpenoid dimers-based toll-like receptor 4 (TLR4) from Dysoxylum parasiticum stem bark.
Toll-Like Receptor 4
/ metabolism
Humans
Animals
Plant Bark
/ chemistry
Mice
Sesquiterpenes
/ pharmacology
HEK293 Cells
Meliaceae
/ chemistry
Plant Extracts
/ pharmacology
Immunologic Factors
/ pharmacology
Cytokines
/ metabolism
RAW 264.7 Cells
Immunomodulating Agents
/ pharmacology
Lipopolysaccharides
/ pharmacology
Dysoxylum parasiticum (Osbeck) Kosterm.
Immunomodulatory TLR4
Proinflammatory cytokines
Sesquiterpenoids and sesquiterpenoid dimers
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
06 Jul 2024
06 Jul 2024
Historique:
received:
16
02
2024
accepted:
24
06
2024
medline:
7
7
2024
pubmed:
7
7
2024
entrez:
6
7
2024
Statut:
epublish
Résumé
In recent decades, the interest in natural products with immunomodulatory properties has increased due to their therapeutic potential. These products have a wider range of pharmacological activities and demonstrate lower toxicity levels when compared to their synthetic counterparts. Therefore, this study aimed to investigate the immunomodulatory effects of sesquiterpenoids (SQs) and sesquiterpenoid dimers (SQDs) isolated from Dysoxylum parasiticum (Osbeck) Kosterm. stem bark on human and murine cells, particularly focusing on toll-like receptor 4 (TLR4). Utilizing the secreted alkaline phosphatase (SEAP) assay on engineered human and murine TLR4 of HEK-Blue cells, antagonist TLR4 compounds were identified, including SQs 6, 9, and 10, as well as SQDs 17 and 22. The results showed that 10-hydroxyl-15-oxo-α-cadinol (9) had a potent ability to reduce TLR4 activation induced by LPS stimulation, with minimal toxicity observed in both human and murine cells. The SEAP assay also revealed diverse immune regulatory effects for the same ligand. For instance, SQs 12, 14, and 16 transitioned from antagonism on human to murine TLR4. The SQs (4, 7, 11, and 15) and SQDs (18-20) offered partial antagonist effect exclusively on murine TLR4. Furthermore, these selected SQs and SQDs were assessed for their influence on the production of proinflammatory cytokines TNF-α, IL-1α, IL-1β, and IL-6 of the NF-κB signaling pathway in human and murine macrophage cell lines, showing a dose-dependent manner. Additionally, a brief discussion on the structure-activity relationship was presented.
Identifiants
pubmed: 38971811
doi: 10.1038/s41598-024-65829-0
pii: 10.1038/s41598-024-65829-0
doi:
Substances chimiques
Toll-Like Receptor 4
0
Sesquiterpenes
0
Plant Extracts
0
Immunologic Factors
0
Cytokines
0
TLR4 protein, human
0
Immunomodulating Agents
0
Lipopolysaccharides
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
15597Informations de copyright
© 2024. The Author(s).
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