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

J Ethnopharmacol. 2018 Jan 10:210:95-106. doi: 10.1016/j.jep.2017.08.034. Epub 2017 Aug 26.

Abstract

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-C18, 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-α) 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-κB 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-α and the expression of proteins iNOS and COX-2. In addition, the biochemical mechanistic study indicated that 1 regulated the NF-κB dependent transcriptional activity through inhibiting the nuclear translocation of p50/p65 dimer and decreasing the phosphorylation of IκB 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-κB and Erk1/2 signaling pathways.

Keywords: Anti-inflammation; NF-κB; Salvia plebeia; Salviplenoid A; Sesquiterpenoid.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / isolation & purification
  • Anti-Inflammatory Agents / pharmacology*
  • Chromatography, High Pressure Liquid / methods
  • Cytokines / metabolism
  • Disease Models, Animal
  • I-kappa B Proteins / metabolism
  • Inflammation / drug therapy
  • Inflammation Mediators / metabolism
  • Lipopolysaccharides / administration & dosage
  • MAP Kinase Signaling System / drug effects
  • Macrophages / drug effects*
  • Macrophages / metabolism
  • Medicine, Chinese Traditional
  • Mice
  • NF-kappa B / metabolism
  • Plant Components, Aerial
  • Plant Extracts / pharmacology
  • RAW 264.7 Cells
  • Salvia / chemistry*
  • Sesquiterpenes / isolation & purification
  • Sesquiterpenes / pharmacology*
  • Signal Transduction / drug effects
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • I-kappa B Proteins
  • Inflammation Mediators
  • Lipopolysaccharides
  • NF-kappa B
  • Plant Extracts
  • Sesquiterpenes
  • Tumor Necrosis Factor-alpha