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.