Hyperhomocysteinemia is considered to be one of the risk factors for inflammatory bowel disease (IBD), it is a chronic, relapsing, and remittent inflammatory disease of the gastrointestinal tract. Citrus sinensis L. has been used traditionally to treat bowel disorders. The present study aims to quantify the phenolic and flavonoid contents of the Citrus sinensis L. fruit (ORF) extract and to evaluate in vitro the antioxidant activity and the anti-inflammatory effect of ORF in vivo on intestinal inflammation induced by hyperhomocysteinemia. The total phenolic and flavonoid contents of the extract were determinated using the spectrophotometric method and the evaluation of antioxidant activity was performed by four methods: DPPH, ABTS, CUPRAC, and reducing power. The inflammatory marker (plasma homocysteine), the reduced glutathione (GSH) content in the liver tissue were measured and the histological sections of the intestines of the mice used were examined to assess the anti-inflammatory activity of ORF. The results of this study showed that the ethanolic extract of ORF possessed high phenolic content and exhibited good antioxidant activity. The use of ORF powder in the in vivo study showed an increase in GSH levels, a decrease in plasma homocysteine levels, and a restoration of the integrity of the intestinal epithelium. Keywords: Hyperhomocysteinemia, Intestinal Inflammation, Citrus sinensis L. fruit, Antioxidant activity, Anti-inflammatory

Introduction:The world is testifying a difficult time with the coronavirus disease (COVID-19) which was declared a pandemic by the World Health Organization (WHO) on March 11 th , 2020. Various symptoms of patients infected with COVID-19 indicated the importance of immune regulation in the human body. So, the immune system is regulated by stimulating the immune cells which has recently been confirmed by the use of quantitative methods for the exploration of the activity of the reticuloendothelial system (RES) with plant extracts by the immune modulation. Methodology: In this study we have evaluated the immunostimulatory activity of Haqua Revitalize Therapy-HART (hot water at 50°) and compared it with vitamin C at the dose 500 mg/kg in mice and determination of catalase concentrations. Results: Our results show that the treatment with hot water and vitamin C increased the phagocytic activity of the reticuloendothelial system (SRE), the corrected phagocytic index α and decreased the rate of carbon clearance (t 1/2) and the concentration of catalase enzyme activity. Conclusion: we concluded that hot water and vitamin C as a preventive and a natural source of antioxidant and they have immunostimulatory activity against pathogens such as virus.