Diverse bioactive metabolites from Callicarpa longifolia var. floccosa: terpenoids, polyketide, and callilongiflocin A as a potent anti-inflammatory diterpenoid targeting IL-17/TNF-α/MAPK signaling with anti-psoriatic activity.

Abstract

Seven previously undescribed compounds comprising four diterpenoids (1-4), two sesquiterpenoids (5, 6), and one polyketide (7), together with four known diterpenoids (8-11), were isolated from Callicarpa longifolia Lamk. var. floccosa Schauer. Their structures and absolute configurations were established using HRESIMS, UV, IR, NMR and ECD calculations. All isolated compounds (1-11) were evaluated for anti-inflammatory activity by LPS-induced RAW264.7 cells. While all compounds inhibited nitric oxide (NO) release to varying degrees, callilongiflocin A (1) exhibited the most potent effects, significantly suppressing the production of NO, pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor-α (TNF-α), and the overexpression of inducible NO synthase (iNOS) in a concentration-dependent manner. Proteomics sequencing revealed that compound 1 modulates IL-17 and TNF signaling pathways. This regulation was further validated by Western blotting, demonstrating 1's inhibition of the common downstream mitogen-activated protein kinase (MAPK) pathway. Furthermore, in an IL-17A plus TNF-α-induced keratinocyte HaCaT model of psoriasis, compound 1 effectively suppressed the inflammatory cytokine IL-6, C-C motif chemokine ligand 20 (CCL-20), and the protein expression of intercellular cell adhesion molecule-1 (ICAM-1), suggesting its potential anti-psoriatic activity.