as Complementary Therapy in Osteoarthritis
Osteoarthritis (OA) is a joint inflammatory disease which limits patient’s activities. Inflammation in OA is associated with angiogenesis. Inflammation stimulates angiogenesis and angiogenesis facilitates inflammation(1) .In inflammation, inflammatory cells (macrophages and mast cells) secrete inflammatory mediators: Interleukin-1β (IL-1β) and Tumor Necrosis Factor-α (TNF-α), which then stimulate matrix metalloproteinases that degrades joint proteoglycan and collagen. (1)
is a shark cartilage extract which contains glycosaminoglycan (GAG) derivatives (chondroitin sulfate), glucosamine and anti-angiogenic factor (heat-stable proteoglycan) which have beneficial effects for joint. Chondroitin sulfate is a kind of GAG required in joint proteoglycan synthesis.(2) It is primarily formed from combining alternating residues of differently sulfated and/or unsulfated residues of glucuronic acid and N-acetylgalactosamine into a polysaccharide chain.(3) Chondroitin sulfates in shark cartilage is different from chondroitin sulfate of other sources such as bovine and porcine. The chondroitin sulfates in shark cartilage are chondroitin 4-sulfate (Chs A), chondroitin 6-sulfate (Chs C) and chondroitin 2,6-disulfate (Chs D, present only in shark cartilage).(4) The beneficial effects of chondroitin sulfate for OA are as anti-inflammatory, anti-degradative, neurite outgrowth promoting activity and cytoprotective. Chondroitin sulfate also has metabolic effects in joint proteoglycan synthesis. (5-9)
Fig. 13. Bioactive Substances in
Proteoglycan is heat stable, stable to extreme pH and stable to proteolytic digestion. This heat-stable proteoglycan has a molecular weight fraction of about 10 kDa that contains the majority of the antiangiogenic activity associated with shark cartilage.(10) The heat stable proteoglycan may help to reduce angiogenesis and inflammation in OA.
There are two kinds of glucosamine in : free glucosamine and N-acetylglucosamine. N-acetylglucosamine can reduce activity of inflammatory mediators more than free glucosamine. Free glucosamine can reduce IL-1β and Nitric oxide (NO) production also Matrix Metalloproteinases (MMPs) activity, whereas N-acetylglucosamine can reduce IL-1β, NO, TNF-α production and Cyclooxygenase-2 (COX-2) activity.(11)
Fig.14. Mechanism of Action of Glycosaminolycan and Proteoglycan in OA