Anti-inflammatory activity of phlomisoside F isolated from Phlomis younghusbandii Mukerjee

• Anti-inflammatory effects of PMF were firstly reported.
• PMF exhibits anti-inflammatory activities on four animal inflammatory models.
• PMF inhibits releases of pro-inflammatory cytokines and enzymes in macrophages.
• PMF exerts anti-inflammatory effects by regulating NF-κB/MAPK pathways.

This study was designed to investigate the anti-inflammatory effect of phlomisoside F (PMF) isolated from Phlomis younghusbandii and to explore the possible pharmacological mechanisms. Anti-inflammatory effects of PMF were evaluated by using carrageenan-induced rat paw edema test, dimethylbenzen-induced ear edema test, acetic acid-induced vascular permeability and cotton pellet granuloma test. Furthermore, the releases of pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β) were determined by ELISA. To explore the potential mechanisms, expressions of iNOS and COX-2 were determined by quantitative real-time PCR and western blotting assays. In addition, the expressions of nuclear p65, cytosolic p65, IκB, p38, p-p38, p-ERK1/2, ERK1/2, JNK and p-JNK were determined by western blotting assay. Our results indicated that PMF administered orally could not only significantly decrease rat paw edema in rats and ear edema in mice, but also reduce the vascular permeability in mice and granuloma weights in rats. In vitro, the releases of LPS-induced pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) and enzymes (iNOS and COX-2) were decreased significantly by PMF treatment in RAW 264.7 cells. In addition, the LPS-induced up-regulations of nuclear p65, p38, p-p38, p-ERK1/2, JNK and p-JNK proteins in RAW 264.7 cells significantly decreased by PMF, and expressions of cytosolic p65 and IκB were obviously up-regulated after treatment with PMF. In conclusion, we suggested that the PMF is a promising potential anti-inflammatory drug, and PMF could down-regulate expressions of pro-inflammatory cytokines and mediators by inhibiting the NF-κB/MAPK pathways.

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