title: Berberine prevents nitric oxide-induced rat chondrocyte apoptosis and cartilage degeneration in a rat osteoarthritis model via AMPK and p38 MAPK signaling.
abstract: Chondrocyte apoptosis is an important mechanism involved in osteoarthritis (OA). Berberine (BBR), a plant alkaloid derived from Chinese medicine, is characterized by multiple pharmacological effects, such as anti-inflammatory and anti-apoptotic activities. This study aimed to evaluate the chondroprotective effect and underlying mechanisms of BBR on sodium nitroprusside (SNP)-stimulated chondrocyte apoptosis and surgically-induced rat OA model. The in vitro results revealed that BBR suppressed SNP-stimulated chondrocyte apoptosis as well as cytoskeletal remodeling, down-regulated expressions of inducible nitric oxide synthase (iNOS) and caspase-3, and up-regulated Bcl-2/Bax ratio and Type II collagen (Col II) at protein levels, which were accompanied by increased adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and decreased phosphorylation of p38 mitogen-activated protein kinase (MAPK). Furthermore, the anti-apoptotic effect of BBR was blocked by AMPK inhibitor Compound C (CC) and adenosine-9-β-D-arabino-furanoside (Ara A), and enhanced by p38 MAPK inhibitor SB203580. In vivo experiment suggested that BBR ameliorated cartilage degeneration and exhibited an anti-apoptotic effect on articular cartilage in a rat OA model, as demonstrated by histological analyses, TUNEL assay and immunohistochemical analyses of caspase-3, Bcl-2 and Bax expressions. These findings suggest that BBR suppresses SNP-stimulated chondrocyte apoptosis and ameliorates cartilage degeneration via activating AMPK signaling and suppressing p38 MAPK activity.
authors.affiliation: Department of Orthopedics, Central Laboratory, Renmin Hospital, Wuhan University, Wuhan, 430060, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.forename: Shi-Qing
authors.initials: SQ
authors.lastname: Liu
authors.forename: Ling
authors.initials: L
authors.lastname: Yu
authors.forename: Bin
authors.initials: B
authors.lastname: He
authors.forename: Shi-Hao
authors.initials: SH
authors.lastname: Wu
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhao
authors.forename: Shao-Qiang
authors.initials: SQ
authors.lastname: Xia
authors.forename: Hong-Jun
authors.initials: HJ
authors.lastname: Mei
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001599:Berberine / Q000494:pharmacology*; D002358:Cartilage, Articular / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D004195:Disease Models, Animal; D007093:Imidazoles / Q000494:pharmacology; D007719:Knee Joint / Q000166:cytology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D010003:Osteoarthritis / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D014740:Vidarabine / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D000470:Alkaloids; D051017:Apoptosis Regulatory Proteins; D007093:Imidazoles; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D001599:Berberine; D009599:Nitroprusside; D009569:Nitric Oxide; D048051:p38 Mitogen-Activated Protein Kinases; D055372:AMP-Activated Protein Kinases; D014740:Vidarabine; C093642:SB 203580