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 by combining the alternative residues of glucuronic acid (both sulfated and unsulfated) 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) In Osteoarthritis, chondroitin sulphate will function as an anti-inflammatory and anti-degradative agent, neurite outgrowth promoting activator, and cytoprotector. Chondroitin sulfate also affect metabolic processes in joint proteoglycan synthesis. (5-9)
Fig. 13. Bioactive Substances in
Proteoglycan is stable in heat, extreme pH and 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.
Free glucosamine and N-acetylglucosamine are two kinds of glucosamine that are found in . 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