Diterpenoid WT-29 isolated from Wedelia exerted anti-inflammatory and anti-allergic activities
Wedelia (Sphagneticola trilobata) is a traditional anti-inflammatory herb native to tropical America. It is commonly used to treat some inflammatory related diseases clinically, such as pertussis, pharyngitis, etc. However, its specific anti-inflammatory mechanism is still unclear. WT-29 (3α-angeloy...
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Veröffentlicht in: | Journal of ethnopharmacology 2024-01, Vol.319, p.117265-117265, Article 117265 |
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Zusammenfassung: | Wedelia (Sphagneticola trilobata) is a traditional anti-inflammatory herb native to tropical America. It is commonly used to treat some inflammatory related diseases clinically, such as pertussis, pharyngitis, etc. However, its specific anti-inflammatory mechanism is still unclear.
WT-29 (3α-angeloyloxy-9β-hydroxyent-kaura-16-en-19-oic acid) is a main bioactive diterpenoid isolated and purified from Wedelia. This study aims to explore the potential anti-inflammatory and anti-allergic properties of WT-29 on RAW264.7 cells stimulated with LPS and P815 cells induced by C48/80, as well as investigating their underlying molecular mechanisms.
The anti-inflammatory mechanism of WT-29 was analyzed and predicted using network pharmacology, and then verified through experiments. The Griess reagent assay was employed to evaluate the impact of WT-29 on the generation of nitric oxide (NO) in RAW264.7 cells induced by LPS, the expression of various inflammatory cytokines and the release of histamine in cells were measured through qRT-PCR and ELISA techniques. The impact of WT-29 on the translocation of the NF-κB p65 protein to the nucleus was assessed through immunofluorescence staining. Western blot technique was utilized to investigate protein expression in inflammation, allergy, and autophagy pathways.
The study found that WT-29 can reduce the secretion of inflammatory factors (NO, iNOS, COX-2, IL-6, IL-1β and TNF-α), inhibit NF-κB activation and MAPK family phosphorylation, and induce autophagy in RAW264.7 cells stimulated with LPS. In addition, it demonstrated that WT-29 could inhibit histamine release and degranulation, as well as inhibit the MAPK family in C48/80-induced P815 cells.
WT-29 isolated from Wedelia exerts anti-inflammatory and anti-allergic effects mainly through NF-κB, Nrf2/Keap-1, MAPK pathways and regulating of autophagy, suggesting that it might be a potential anti-inflammatory and anti-allergic agent and could be used as medicine or health benefit product.
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•Wedelia is an anti-inflammatory herb to treat inflammatory related diseases.•WT-29 is a main anti-inflammatory diterpenoid of Wedelia.•WT-29 can inhibit the NF-κB pathway and activate the Nrf2/HO-1 pathway.•WT-29 exerts anti-inflammatory and anti-allergic effects through MAPK pathway.•The anti-inflammatory effect of WT-29 was enhanced in combination with autophagy. |
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ISSN: | 0378-8741 1872-7573 |
DOI: | 10.1016/j.jep.2023.117265 |