Diterpenoid WT-29 isolated from Wedelia exerted anti-inflammatory and anti-allergic activities

Ethnopharmacological relevance: 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. Aim of the study: WT-29 (3 alpha-angeloyloxy-9 beta-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.Methods: 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-kappa B 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.Results: The study found that WT-29 can reduce the secretion of inflammatory factors (NO, iNOS, COX-2, IL-6, IL1 beta and TNF-alpha), inhibit NF-kappa B 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.Conclusion: WT-29 isolated from Wedelia exerts anti-inflammatory and anti-allergic effects mainly through NF kappa B, Nrf2/Keap-1, MAPK pathways and regulating of autophagy, suggesting that it might be a potential antiinflammatory and anti-allergic agent and could be used as medicine or health benefit product.

Automated summary

The study found that WT-29 isolated from Wedelia exhibits anti-inflammatory and anti-allergic effects mainly through the regulation of NF kappa B, MAPK pathways, and autophagy. This suggests that WT-29 may have potential as an anti-inflammatory and anti-allergic agent, and could be used as a medicine or health benefit product.