الفهرس 
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Abstract
Knee osteoarthritis is a common cause of pain and long-term disability in elderly, and the incidence among middle-aged adults is considerable (Leslile, 2000) . Osteoarthritis is not a simple consequence of “wear and tear” or aging- the presence of cytokines suggests a role of inflammation (Pincus, 2001). It is of utmost importance to find out more about pathogenesis of the disease and thus allow the discovery of new treatment attempting to restrict its progression (Pelletier et al., 2001). Reactive oxygen species (ROS) are implicated in pathogenesis of osteoarthritis (Tiku et al., 2000) . Nitric oxide (NO) synthesis increases in OA (Fermor et al., 2001) with increase its serum concentration (Erosy et al., 2002) . Conventional medication used to treat OA can effectively control symptoms of the disease in some cases but these drugs, including NSAIDs have many side effects (Hungin and Kean, 2001) . This necessitates a real need for safe and effective treatment of osteoarthritis (Long et al., 2001). Herbal medicine or “phytotherapy” has been identified as having potential benefit in treatment of osteoarthritis (Little and Parsons, 2001) . One of the most effective botanicals used to moderate symptoms of OA are Boswellia and Turmeric as a natural leukotrienes inhibitors (Shweizer et al., 2001) . The objectives of this work is to evaluate the efficacy of Boswellia and Turmeric as a natural leukotrienes inhibitors in treatment of knee OA and assesment by clinical parameters in addition to detection of serum level of antioxidant enzyme (superoxide dismutase), free radical damage marker (nitric oxide) and T cell receptors (CD4+ T cells, CD45RO+ T cells) . This study was conducted on 45 adult patients with knee OA and 10 normal individuals (controls) . They were selected from the outpatient clinic of Rheumatology and Rehabilitation at Mansoura University Hospital. They were divided into the following 3 groups : Group I : 30 OA patients; treatment group Group II : 15 OA patients; placebo group Group III : 10 healthy normal subjects (control) Patients having diabetes mellitus, hypertension, peptic ulcer, renal failure, liver disorder were excluded from the study . After selection, the patients were evaluated weekly for a pre-treatment period of 2 weeks during which all their previous drugs are withdrawn . After informed consents, the patients were included into a double-blind, randomised, cross over study of treatment with a herbal formulation (Natural leukotrienes inhibitors) which is prepared from highly safe and pure extracts from Boswellia carteri and Turmeric in 500 mg hard gelatin capsules. Two (500 mg) capsules were taken every 8h after meals . Treatment was given for 3 months . In addition to thorough history taking and clinical examination. All were subjected to the following invetsigations : 1- Routine investigations : a- Erythrocyte sedmintation rate (ESR) b- Serum uric acid 2- Special laboratory investigations : i) Antioxidant enzyme : - Superoxide dismutase (SOD) ii) Free radical damage marker -Nitric oxide (nitrite & nitrate) iii) T cell receptors : - CD4+ T cells - CD45RO+ T cells iv) Apoptosis : - sFas/Apo-1/CD95 (ELISA) 3- Radiological investigations : (Plain x-ray of both knees) The results could be summarized as follows : I) Clinically : The outcome of group I (OA patients; treatment group) after one month of treatment was significant improvement of pain free walking time (P = 0.0145) After two months of therapy, there was a highly significant reduction of severity of pain on passive movement (P = 0.001), severity of pain on active movement (P = 0.004), degree of tenderness (P = 0.001) and highly significant prolongation of pain free walking time (P = 0.0012) . At the end of three months, there was a significant reduction of grade of knee effusion (P = 0.028), with highly significant reduction of pain on passive movement (P < 0.001), pain on active movement (P < 0.001), degree of tenderness (P < 0.001) and significant prolongation of pain free walking time (P < 0.001) . The outcome of group II (OA patients; placebo group) was no significant difference in the evaluation parameters after one month, two months and three months of placebo treatment . II) Laboratory : Serum NO nitrite and nitrate were significantly higher in group I and group II (P = 0.002, P < 0.001 respectively) than control group . After three months of treatment, there was a highly significant decrease in serum nitrite and nitrate in group I after end of therapy than before treatment (P < 0.001) . Also there was a highly significant decrease in serum nitrite and nitrate in group I than group II (P < 0.001) Serum SOD was significantly higher in both group I and group II (P < 0.001) than control group . After three months of treatment, there was a highly significant increase in serum SOD in group I after end of therapy (P < 0.001) than before therapy. Also there was a highly significant improvement of serum SOD in group I (P < 0.001) than group II Serum CD4+ T cells and CD45RO+ T cells were significantly higher in group I and group II (P < 0.001) than control group. After three months of treatment, there was a highly significant decrease in serum CD4+ T cells and CD45RO+ T cells in group I after therapy (P < 0.001) than before therapy . Also, there was a highly significant decrease in both serum CD4+ T cells and CD45RO+ T cells in group I (P < 0.001) than group II. Serum sFas at zero time and at 72h were significantly lower in group I and group II (P < 0.001) than control group . After three months of treatment, there was a highly significant increase in serum sFas in group I after three months of treatment at zero time and at 72h (P < 0.001) than before treatment . Also, there was a highly significant increase in serum sFas in group I at zero time and at 72h (P < 0.001) than group II . Conclusions : • Boswellia and Turmeric are effective botanicals can be used to moderate symptoms of osteoarthritis as manifested by improvement in degree of pain on active and passive movement, pain free walking time, tenderness and effusion. • Free radical damage marker (NO) is considered to be high in serum of OA patients. Boswellia and Turmeric produced positive impact on NO production as demonstrated by decrease its serum level . • Antioxidants (SOD) in OA patients is considered to be high but not sufficient to overcome the oxidative stress . Its serum level increased with Boswellia and Turmeric (anti-inflammatory and antioxidant) . • Serum TCR in OA patients was observed to be high as a marker of inflammation and this might support the postulation that immunological reaction has a role in the pathogenesis of osteoarthritis . Serum TCR decreased after treatment by Boswellia and Turmeric documenting its anti-inflammatory effects. • It is concluded that serum levels of free radical damage marker (NO), antioxidant (SOD) and T cell receptors (CD4+, CD45RO+ T cells) have a role in pathogenesis of OA . These markers may be used in the follow-up of the course of disease and to measure the efficacy of therapies in clinical practice . • It is also concluded that Boswellia and Turmeric are efficient (anti-inflammatory and antioxidant), safe (as non of 30 patients included in this study demonstrated significant side effects) and economic (less expensive cyclooxygenase (COX) inhibitor than pharmaceutical COX-inhibitor drugs) in treatment of knee OA