Biological activities of Phoenix dactylifera and Treg in Rheumatoid arthritis induced by hyperhomocysteinemia and formalin and on tumoral process

Abstract

Inflammation plays an important role in various diseases, such as rheumatoid arthritis, atherosclerosis and asthma, which all show a high prevalence globally and the absence of the immune tolerance which is insured by the lymphocyte Treg. This tolerance protects the selfantigens from the immune system’s reaction. In addition, some chronic inflammatory diseases are recently found to be associated with an increased levels of hs-CRP and plasma homocysteine. In the present study, we evaluated the in vivo, the effect of two varieties of Phoenix dactylifera (Azarza variety grown in Ghardaia and variety Homayra grown in Adrar) on the toxicity using the up and down test, the immunomodulatory activity of the extracts using the carbon clearance from the blood, antioxidant by the measurement of the GSH from liver’s homogenate, anti-inflammatory activity and anti-arthritis by the formalin and L-methionine test in Albino mice. Also we have carried a study in vitro to establish the anti-proliferative effect of the methanolic and acetone extracts dates on liver cancer cell line (HepG2), breast cancer cell line (MCF7) and healthy cells, endothelial cells (HUVEC) and hepatocytes (hNHEPS). In addition to this work, we tested the effect of Phoenix dactylifera extracts on apoptotic genes (Bcl2 and BAX) and on the differentiation of human naïve lymphocyte T CD4+ into regulatory lymphocytes Treg. The results showed that the extracts of Phoenix dactylifera have no toxic effect at a dose of 2000mg/kg, also we found that the extracts increased significantly the phagocytic activity of the reticuloendothelial system, and release of glutathione reduced (GSH) from the liver. Furthermore, the extracts of Phoenix dactylifera studied reveal correction on the inflammation associated with hyperhomocysteinemia presented by a significant decrease in the size of the edema induced by formalin injection and a significant decrease in the hs- CRPvalues and homocysteine Hcy (p ≤ 0.05) in mice treated compared to controls, where it was observed that the administration of L-methionine 400 mg/kg caused a worsening of inflammation presented by a significant increase in protein C-reactive (CRP) p≤0,05 and a significant increase in homocysteine (Hcy) p≤0,05. Our results demonstrate a significant inhibition of edema of mice paws treated with our extracts with a decrease in the Anti-CCP values. The results indicate that treatment with six different concentrations (2 mg/100mL, 4 mg/100mL, 7.5 mg/100mL, 8 mg/100mL, 16 mg/1 00mL and 20 mg/100mL) inhibited the growth of tumor cells but had no toxicity to healthy cells.