Joint related diseases such as arthritis, contributes a large segment of an orthopaedic’s caseload. Arthritic diseases interfere with our daily activities as it causes enormous burdens in terms of pain, crippling and disability. Osteoarthritis (OA), the most common form of arthritis is the leading cause of chronic disability at older age. It is estimated that the prevalence of symptomatic knee OA in population above the age of 65 is 30 % and women suffer from knee OA two times higher than men. OA is characterized by a slow progressive degeneration of articular cartilage that leads to joint signs and symptoms, including changes at the subchondral bone and synovium. OA commonly affects the hands, spine, knees and hips  with other joints such as the wrist, elbows, and shoulders less frequently involve. While all tissues involving the synovial joint are affected, the degeneration of articular cartilage is the main pathological feature in this disease. The breakdown of articular cartilage in OA may start as a focal lesion and progressively extend to involve multiple components of the synovial joints such as alteration in the bone underneath the cartilage, development of marginal outgrowths, osteophytes and increased thickness of subchondral bone .
Research has proven that although age is the substantial risk factor for the account of this disease, other factors are also known to affect the progression of OA which includes obesity, mechanical factors such as trauma or injury to the joint  and genetic abnormalities . However, the exact pathogenesis of this disease is still poorly understood. But latest detection methods showed that OA does not only result from the breakdown of articular cartilage due to aging and biomechanical factors, but is also caused by elevated levels of hydrolytic enzymes activity [4, 5]. Hyaluronidase or hyaluronate glycanohydrolase (EC 184.108.40.206) is large neglected class of hydrolytic enzymes that belongs to the family of degradative endoglucosaminidase. This enzyme was found to be one of the most predominant glycosidase present during cytokine-induced ECM degradation associated with the synovial joint disease . Hyaluronidase is also widespread in nature, which present abundantly in mammals, insects, leeches and bacteria [7, 8]. Hyaluronan or hyaluronic acid (HA), the major building blocks of the matrix components in the ECM are degraded upon exposure to free radicals and hyaluronidases (predominantly HYAL1, HYAL2, HYAL3). Hyaluronidases break down HA excessively resulting in the degeneration and gradual loss of articular cartilage leading to OA.
Besides, destruction of the ECM in cartilage tissue is also caused by the locally produced matrix metalloproteinases (MMPs). MMPs are a group of proteases which consists of collagenases (e.g. MMP-1 and MMP-13), stromelysins (e.g. MMP-3), gelatinases and membrane type MMPs . MMPs have been implicated in the biophysical degradation of ECM and the collagenous framework of articular cartilage. Activated MMPs are capable of cleaving most of the components in the ECM including type II collagen and aggrecan. Stromelysin-1 (MMP-3) cleaves proteoglycans (PGs), collagens, gelatins and link protein of aggrecan, whereas collagenase-3 (MMP-13) cleaves type II collagen and aggrecan at particular sites . In cases of degenerative joint disease, such as OA, the expression and synthesis of both MMP-3 and MMP-13 are increased.
Currently, OA is being treated using conventional therapeutic interventions which include drug treatments and injectable agents such as glucocorticoids and hyaluronan. Drug therapies although costly, have extensively being used in mild to moderate cases where the use of drug treatments is to control pain and prolong disease progression. Although drug medication have proven to be effective in controlling pain, the prolong use of this drugs have been associated with serious adverse effects, mainly ulcer formation and gastrointestinal complications . Hence, there appears to be a need for drugs with low toxicity and effective in the treatment of OA. Therefore, patients are turning increasingly to alternative medications.
The uses of natural products in treating such diseases have been gaining attention due to reasons such as they are found in nature and safer. Furthermore, report on incidences of adverse effects from consumption of natural products seems low as it may provide a much needed alternative for patients with long-term chronic OA . Hence, in this project Payena dasyphylla a selected Malaysian tree locally known as “nyatoh” has been studied for its inhibitory effect on hyaluronidase enzyme activity and MMPs protein expressions as well as its anti-radical scavenging activity.