Kolaviron Improves Morbidity and Suppresses Mortality by Mitigating Oxido-Inflammation in BALB/c Mice Infected with Influenza Virus.

Abstract

Influenza A viruses (IAV) induce cytokine storm and host's intracellular redox imbalance to ensure continuous replication and survival, leading to severe immunopathology and death. The unpredictability of broad-spectrum vaccines, the emergence of drug-resistant and/or more virulent strains, the prevalence of the amantadane-resistant IAV, and the prohibitive cost of available drugs especially in resource-poor countries necessitate exploring drugs with novel action mechanisms as anti-influenza agents. This study presents the protective role of kolaviron (KV), a natural antioxidant and anti-inflammatory agent from Garcinia kola seeds, on BALB/c mice challenged with influenza A/Perth/H3N2/16/09 (Pr/H3N2) virus. KV at 400 mg/kg was administered orally to groups of BALB/c mice for 3 days, 3 h, and 1 h prior to infection with 1LD50 or 3LD50 (14-day study) and 5LD50 (6-day study) Pr/H3N2. Pr/H3N2 in the lungs was detected by hemagglutination assay, while oxidative stress and inflammatory biomarkers were assayed in both lungs and liver. Infected mice treated with KV progressively increased in weight with minimal mortality. Single-dose administration of KV at 1 h or 3 h before viral challenge and 3 days pretreatment improved lung aeration and reduced lung consolidation as well as inflammatory cells infiltration in a way that had minimal impact on viral clearance, but attenuated myeloperoxidase activity and nitric oxide production via priming of reduced glutathione levels, thus enhancing the preservation of function in the lungs and liver. This study suggests that KV may be effective for delaying the development of clinical symptoms of influenza virus, and this may be through a mechanism unrelated to those deployed by the existing anti-influenza drugs but closely associated to its antioxidant and immunomodulatory properties.