title: A wogonin-rich-fraction of Scutellaria baicalensis root extract exerts chondroprotective effects by suppressing IL-1β-induced activation of AP-1 in human OA chondrocytes.
abstract: Osteoarthritis (OA) is a common joint disorder with varying degrees of inflammation and sustained oxidative stress. The root extract of Scutellaria baicalensis (SBE) has been used for the treatment of inflammatory and other diseases. Here, we performed activity-guided HPLC-fractionation of SBE, identified the active ingredient(s) and investigated its chondroprotective potential. We found that the Wogonin containing fraction-4 (F4) was the most potent fraction based on its ability to inhibit ROS production and the suppression of catabolic markers including IL-6, COX-2, iNOS, MMP-3, MMP-9, MMP-13 and ADAMTS-4 in IL-1β-treated OA chondrocytes. OA chondrocytes treated with F4 in the presence of IL-1β showed significantly enhanced expression of anabolic genes ACAN and COL2A1. In an in vitro model of cartilage degradation treatment with F4 inhibited s-GAG release from IL-1β-treated human cartilage explants. The inhibitory effect of F4 was not mediated through the inhibition of MAPKs and NF-κB activation but was mediated through the suppression of c-Fos/AP-1 activity at transcriptional and post transcriptional levels in OA chondrocytes. Purified Wogonin mimicked the effects of F4 in IL-1β-stimulated OA chondrocytes. Our data demonstrates that a Wogonin-rich fraction of SBE exert chondroprotective effects through the suppression of c-Fos/AP-1 expression and activity in OA chondrocytes under pathological conditions.
authors.affiliation: Department of Anatomy &Neurobiology, Northeast Ohio Medical University, 4209 St Rt 44, Rootstown, OH 44272, USA.
authors.forename: Nazir M
authors.initials: NM
authors.lastname: Khan
authors.affiliation: Department of Anatomy &Neurobiology, Northeast Ohio Medical University, 4209 St Rt 44, Rootstown, OH 44272, USA.
authors.forename: Abdul
authors.initials: A
authors.lastname: Haseeb
authors.affiliation: Department of Anatomy &Neurobiology, Northeast Ohio Medical University, 4209 St Rt 44, Rootstown, OH 44272, USA.
authors.forename: Mohammad Y
authors.initials: MY
authors.lastname: Ansari
authors.affiliation: Department of Anatomy &Neurobiology, Northeast Ohio Medical University, 4209 St Rt 44, Rootstown, OH 44272, USA.
authors.forename: Tariq M
authors.initials: TM
authors.lastname: Haqqi
mesh_terms: D002478:Cells, Cultured; D005591:Chemical Fractionation / Q000379:methods; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D044950:Flavanones / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D010003:Osteoarthritis / Q000473:pathology; D010936:Plant Extracts / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry*; D020011:Protective Agents / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D031364:Scutellaria baicalensis / Q000737:chemistry*; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D044950:Flavanones; D053583:Interleukin-1beta; D015850:Interleukin-6; D010936:Plant Extracts; D020011:Protective Agents; D017382:Reactive Oxygen Species; C499814:Scutellaria baicalensis extract; D018808:Transcription Factor AP-1; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; C085514:wogonin