title: Farrerol inhibits IL-6 and IL-8 production in LPS-stimulated human gingival fibroblasts by suppressing PI3K/AKT/NF-κB signaling pathway.
abstract: OBJECTIVE
  Farrerol, a new type of 2,3-dihydro-flavonoid isolated from rhododendron, has been shown to have anti-bacterial and anti-inflammatory activities. In the present study, we investigated the anti-inflammatory effects of farrerol on the production of IL-6 and IL-8 in human gingival fibroblasts (HGFs) treated with lipopolysaccharide (LPS).
  
  
  METHODS
  The cytotoxicity of farrerol was determined using the MTT assay. The production of IL-6 and IL-8 was measured using ELISA and qRT-PCR. The effects of farrerol on PI3K, Akt phosphorylation, and NF-κB activation were detected using western blotting analyses.
  
  
  RESULTS
  These results showed that farrerol inhibited LPS-induced IL-6 and IL-8 production in a dose dependent manner. LPS-induced NF-κB activation was suppressed by farrerol. Furthermore, farrerol suppressed LPS-induced PI3K and Akt phosphorylation, which are upstream molecules of NF-κB.
  
  
  CONCLUSIONS
  These results indicated that farrerol attenuated IL-6 and IL-8 production by inhibition of PI3K and AKT phosphorylation, resulting in an inhibition of NF-κB activation. Farrerol may be a therapeutic agent for the treatment of periodontal disease.
authors.affiliation: Department of Pharmacy, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250000, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, The Second Hospital of Shandong University, Jinan, Shandong 250000, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, The Second Hospital of Shandong University, Jinan, Shandong 250000, China. Electronic address: yujinlongwx@163.com.
authors.forename: Jin-Long
authors.initials: JL
authors.lastname: Yu
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects*; D005881:Gingiva / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010510:Periodontal Diseases / Q000628:therapy; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D000093242:Interleukin-6 Inhibitors
chemical_list: D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D002867:Chromones; D015850:Interleukin-6; D016209:Interleukin-8; D008070:Lipopolysaccharides; D016328:NF-kappa B; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D000093242:Interleukin-6 Inhibitors; C015881:farrerol
keywords: Farrerol; Human gingival fibroblasts; IL-6; NF-κB; PI3K