Protective Effects of Citrus Flavonoid Hesperidin in Enterocytes After Induction with TNF-? and IFN-? Which Mimic the COVID-19 Disease

Abstract

BACKGROUND/AIMS: Coronavirus disease (COVID-19) is caused by a virus and exhibits various symptoms such as cough, fever, and chills. Flavonoids have a potential inhibitory effect on coronaviruses. In this study, we determined the effects of hesperidin on enterocyte cells (IEC) after tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma induction which mimics the severe acute respiratory therapy-coronavirus-2 (SARS-CoV-2) infection. MATERIALS AND METHODS: The IEC-6 were treated with 50 ng/mL of TNF-alpha and 100 ng/mL of IFN-y for 48 h to mimic inflammatory shock similar to COVID-19 disease. IEC-6 cells were cultured as control, COVID-19 disease mimic, hesperidin prophylactic, or treated groups. The cytotoxicity effect of hesperidin was analyzed using an MTT assay. Serum levels of TNF-alpha and interleukin (IL)8 were evaluated using ELISA. The distributions of TNF-alpha, IFN-y, IL-1ss, Insulin-like growth factor-I, and caspase-3 were analyzed by indirect immunoperoxidase staining. RESULTS: Both TNF-alpha and IL8 levels were higher in TNF-alpha and IFN-y induction of enterocyte culture medium than in the control. Lesser immunoreactivity of TNF-alpha was detected in the treatment group which hesperidin applicate after TNF-alpha and IFN-y combination. While IL-1 immunoreactivity was similar in both the hesperidin prophylactic and treatment groups, lesser immunoreactivity of TNF-alpha was observed in the hesperidin treatment group. Both IFN-y and vascular endothelial growth factor A immunoreactivities were also decreased in the hesperidin treatment group. CONCLUSION: We found that hesperidin had anti-inflammatory and cell protection effects in IEC after TNF-alpha and IFN-gamma induction which mimics the model of SARS-CoV-2 infection. Therefore, hesperidin could be used to reduce gastrointestinal system symptoms in COVID-19 disease.