Inhibitory effects of polyphenol punicalagin on type-II collagen degradation in vitro and inflammation in vivo

• Published in: Chemico-biological interactions 2013-09, Vol.205 (2), p.90-99
• Main Authors: Jean-Gilles, Dinorah, Li, Liya, Vaidyanathan, V.G., King, Roberta, Cho, Bongsup, Worthen, David R., Chichester, Clinton O., Seeram, Navindra P.
• Format: Article
• Language: English
• Subjects: animal models; Animals; anti-inflammatory activity; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Arthritis; Arthritis, Experimental - drug therapy; Binding Sites; body measurements; body weight; cartilage; Cartilage - drug effects; Cartilage - metabolism; Cartilage degradation; catalytic activity; Cattle; collagen; Collagen Type II - chemistry; Collagen Type II - metabolism; collagenase; culture media; ellagic acid; Ellagic Acid - pharmacology; Ellagitannins; extracellular matrix; Hydrolyzable Tannins - pharmacology; Inflammation; interleukin-1beta; Male; Matrix Metalloproteinase 13 - metabolism; Matrix Metalloproteinase Inhibitors - pharmacology; Models, Molecular; Polyphenols; Polyphenols - pharmacology; Pomegranate; proteoglycans; Proteoglycans - metabolism; Proteolysis - drug effects; Rats; Rats, Inbred Lew; surface plasmon resonance
• ISSN: 0009-2797; 1872-7786
• DOI: 10.1016/j.cbi.2013.06.018

•Polyphenol punicalagin inhibited type-II collagen degradation in vitro.•Punicalagin has multiple binding interactions with type-II collagen by SPR.•Molecular docking studies show punicalagin binds with type-II collagen.•Punicalagin inhibited inflammation in a rat model. 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