Anti-inflammatory sesquiterpenoids from the Traditional Chinese Medicine Salvia plebeia: Regulates pro-inflammatory mediators through inhibition of NF-κB and Erk1/2 signaling pathways in LPS-induced Raw264.7 cells

Ethnopharmacological relevance: Salvia plebeia R. Brown, a traditional Chinese medicinal herb, has been used to treat inflammatory diseases such as cough, hepatitis, and diarrhea for a long history. Aim of the study: The aim of the present study was to isolate and identify potential anti-inflammatory agents from the herb of S. plebeia, which may have contributed to its folk pharmacological use in the treatment of inflammatory diseases. Material and methods: The aerial parts of S. plebeia were extracted with 95% ethanol and separated by silica gel, RP-C-18, Sephadex LH-20, and HPLC. The structures of the isolated compounds were elucidated by extensive spectroscopic analysis (MS, NMR, and X-ray). Anti-inflammatory activities of all compounds were evaluated by the model of LPS-induced up-regulated of NO in Raw264.7 macrophages. The expression levels of cytokine (TNF-alpha) and proteins (iNOS and COX-2) were assessed by ELISA kit and Western blotting analysis, respectively. Furthermore, the influences of salviplenoid A (1) on NF-kappa B and MAPK signaling pathways were determined by Western blotting analysis and immunofluorescence assay. Results: Six new (1 - 6, salviplenoids A-F) and ten known (7-16) sesquiterpenoids were isolated from the herb of S. plebeia. The absolute configurations of compounds 1, 2, and 7 were determined by X-ray diffraction. The new eudesmane-type sesquiterpenoid, salviplenoid A (1), significantly decreased the release of NO and TNF-a and the expression of proteins iNOS and COX-2. In addition, the biochemical mechanistic study indicated that 1 regulated the NF-kappa B dependent transcriptional activity through inhibiting the nuclear translocation of p50/p65 dimer and decreasing the phosphorylation of I kappa B and Erk1/2. Conclusions: Among all sesquiterpenoids isolated from S. plebeian, the new salviplenoid A (1) exhibited the most potent anti-inflammatory activity in LPS-induced Raw264.7 cells via inhibition of NF-kappa B and Erk1/2 signaling pathways.