Immunomodulatory effect of Moringa oleifera and Phyllanthus niruri extracts on anti-HBV cytokine production by human peripheral blood mononuclear cells

Background: Chronic hepatitis B (HBV) infection is a leading cause of cirrhosis and liver cancer globally. The current approved drugs for chronic HBV management include pegylated interferons and nucleoside analogs but these have limited efficacies and some adverse side effects. There is an urgent need to find safer and more effective antivirals for chronic HBV management. This study aimed to evaluate the in vitro immunostimulatory properties of the aqueous and ethanolic leaf extracts of the plants Moringa oleifera and Phyllanthus niruri on human peripheral blood mononuclear cells (PBMCs) from chronic HBV-infected persons yet to commence therapy and HBV-negative persons. Methods: Plant extracts were freeze-dried and stock solutions prepared for phytochemical analysis. Extracts were used to stimulate cultured PBMCs from HBV-infected and HBV-negative persons and the levels of selected cytokines in culture supernatants measured by a multiplexed Luminex assay. The MTT assay was used to assess extract cytotoxicity. Results: Aqueous and ethanol extracts of both plants were not cytotoxic but rather increased cell metabolic activity. The extracts induced the release of IL-6, IL-1β, IFN-γ, IL-10, TNF-α and IFN-α in PBMCs from both healthy individuals and chronic HBV patients, but cytokine levels were in most instances significantly higher in PBMCs from healthy individuals compared to HBV infected persons and may be related to the reduced immune responsiveness associated with chronic HBV infection. The reduced responsiveness of immune cells from chronic HBV-infected persons to stimulation may explain viral persistence and development of the chronic state. Overall, leaf extracts from both plants were safe and stimulated the release of HBV replication-limiting cytokines and may be important for chronic HBV management. Conclusions: These findings lay the foundation for the potential integration of these extracts into HBV management strategies and provide promising data for future therapeutic development aimed at improving immune responses in chronic HBV patients.