Biological activities of some medicinal plants on rheumatoid arthritis induced by hyperhomocysteinemia and formalin and on tumoral process

Abstract

Inflammation is an immune response that underlies a wide variety of physiological and pathological processes; there is growing evidence suggesting that inflammation plays a key role in the pathogenesis of rheumatoid arthritis, cardiovascular diseases and cancer. In addition, some chronic inflammatory diseases are recently found to be associated with an increased level of homocysteine (hyperhomocysteinemia). In fact, a link seems to connect homocysteine (Hcy) and the immuno-inflammatory activation, when inflammatory activation may contribute to Hcy increase, Hcy, in its turn, may act as a pro-inflammatory molecule cooperating to the injury. Natural products from medicinal plants play a crucial role in drug discovery; the investigation of medicinal plants products has resulted in wide number of compounds with promising biological activities. In the present study we evaluated in vivo the effect of three Algerian medicinal plants namely Argania spinosa, Citrullus colocynthis, and Boswellia serrata harvested in Tindouf andTiguentourine respectively on the toxicity, immunostimulatory activity and pain. Another work was about a comparative screening of the immunomodulatory activity of the three oils which were compared with virgin olive oil. The toxicity assessment was performed using up and down test in Albinos rats , the immunomodulatory activity was assessed in the reticulo-endothelial system using carbon clearance assay, the analgesic effect was studied by acetic acid induced writhing test in Mus musculus mice. The results obtained showed that the extracts of medicinal plants did not present any toxic effect with the administration of the dose 2000mg/kg; also increased significantly the phagocytic activity in dose dependent manner and have analgesic effect by reducing significantly the writhing in mice induced by acetic acid. Also we have obtained that the phagocytic activity was increased very highly significantly in the groups of rats treated with Boswellia serrata (200mg/kg) and olive oil (100mg/kg) P≤0,001. Another study was carried on the anti-inflammatory activity of the three plants extracts which was assessed using an acute model of inflammation which is xylene ear oedema and other was carried with only Argania spinosa seeds on arthritis which was assessed in two chronic models of inflammation consisting of formalin induced arthritis and formalin induced arthritis associated with L- methionine induced hyperhomocysteinemia. The results obtained demonstrated that there was significant inhibition of ear oedema caused by the three extracts treatment. Our research also revealed that administration of L- methionine at dose 400mg/kg caused aggravation of inflammation presented by very high significantly increase of C-reactive proteins (CRP) P≤0,001 and high significantly increase of homocysteine (Hcy) P ≤0,01, in addition , necrosis, degeneration and inflammatory cells accumulation were observed in the articular cartilage, but the treatment by crude extract of Argania spinosa seeds at doses of 100 and 200 mg/kg attenuate this effect reducing the paw thickness in both models of chronic arthritis and this also was confirmed by normal histological sections. Moreover, in the present thesis, we conducted a study in vitro to evaluate the anti-proliferative effect of the three oils on the T-cell acute lymphoblastic leukemia cell lines and on signaling proteins (NOTCH 1 and ERK1/2).The results revealed that treatment with the different oils at the dose of 100μg/ml inhibited the growth of tumor cells, but the Argania spinosa oil only reduced the expression levels of signaling proteins ERK1/2 and NOTCH1.