title: Inhibitory effects of polyphenol punicalagin on type-II collagen degradation in vitro and inflammation in vivo.
abstract: Cartilage destruction is a crucial process in arthritis and is characterized by the degradation of cartilage proteins, proteoglycans, and type II collagen (CII), which are embedded within the extracellular matrix. While proteoglycan loss can be reversed, the degradation of CII is irreversible and has been correlated with an over-expression and over-activation of matrix metalloproteinases (MMPs). Among the various MMPs, the collagenase MMP-13 possesses the greatest catalytic activity for CII degradation. Here we show that the pomegranate-derived polyphenols, punicalagin (PA) and ellagic acid (EA), inhibit MMP-13-mediated degradation of CII in vitro. Surface plasmon resonance studies and molecular docking simulations suggested multiple binding interactions of PA and EA with CII. The effects of PA on bovine cartilage degradation (stimulated with IL-1β) were investigated by assaying proteoglycan and CII release into cartilage culture media. PA inhibited the degradation of both proteins in a concentration-dependent manner. Finally, the anti-inflammatory effects of PA (daily IP delivery at 10 and 50mg/kg for 14days) were tested in an adjuvant-induced arthritis rat model. Disease development was assessed by daily measurements of body weight and paw volume (using the water displacement method). PA had no effect on disease development at the lower dose but inhibited paw volume (P<0.05) at the higher dose.
authors.affiliation: Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, United States.
authors.forename: Dinorah
authors.initials: D
authors.lastname: Jean-Gilles
authors.forename: Liya
authors.initials: L
authors.lastname: Li
authors.forename: V G
authors.initials: VG
authors.lastname: Vaidyanathan
authors.forename: Roberta
authors.initials: R
authors.lastname: King
authors.forename: Bongsup
authors.initials: B
authors.lastname: Cho
authors.forename: David R
authors.initials: DR
authors.lastname: Worthen
authors.forename: Clinton O
authors.initials: CO
authors.lastname: Chichester
authors.forename: Navindra P
authors.initials: NP
authors.lastname: Seeram
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001169:Arthritis, Experimental / Q000188:drug therapy; D001665:Binding Sites; D002356:Cartilage / Q000187:drug effects / Q000378:metabolism; D002417:Cattle; D024043:Collagen Type II / Q000737:chemistry / Q000378:metabolism*; D004610:Ellagic Acid / Q000494:pharmacology; D047348:Hydrolyzable Tannins / Q000494:pharmacology*; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology; D008958:Models, Molecular; D059808:Polyphenols / Q000494:pharmacology; D011509:Proteoglycans / Q000378:metabolism; D059748:Proteolysis / Q000187:drug effects; D051381:Rats; D011917:Rats, Inbred Lew
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D024043:Collagen Type II; D047348:Hydrolyzable Tannins; D061965:Matrix Metalloproteinase Inhibitors; D059808:Polyphenols; D011509:Proteoglycans; D004610:Ellagic Acid; C115642:punicalagin; D053509:Matrix Metalloproteinase 13; C507083:Mmp13 protein, rat
keywords: Arthritis; Cartilage degradation; Ellagitannins; Inflammation; Polyphenols; Pomegranate