Mechanistic perspective of the oxido‐immunopathologic resolution property of kolaviron in mice influenza pneumonitis

Abstract

Implicated in influenza-associated pathology are innate defence overzealousness and unabated secretion of oxidative tissue-sensitive antimicrobial agents. At different time points, mice were pre-treated with kolaviron (400 mg/kg), a natural antioxidant and anti-inflammatory agent, and subsequently challenged with 2 LD influenza A/H3N2/Perth/16/09 virus. After euthanasia at day 6, blood, lungs, liver and spleen were collected and processed for biochemical, immunohistochemical and flow cytometric assessment of redo-inflammatory imbalance, cytokine storm indices and T helper 1 host response. Previously kolaviron was reported to delay mortality onset, improve morbidity and attenuate myeloperoxidase activity and nitric oxide production with minimal impact on viral clearance. This study additionally confirmed nitric oxide, but not hydrogen peroxide, as the major culprit implicated in influenza virus-induced oxido-pathology. Systemic effect of the sustained inflammation and nitrosative stress was more prominent in the spleen and lung than in the liver of mice infected with A/H3N2/Perth/16/09. Influential to immunopathology was heightened pulmonary expression of IL-1β, RANTES, IL-10, MCP-1, NF-κB, iNOS and COX-2. However, kolaviron combated the influenza-established nitrative stress, reversed the elicited cytokine storm and restored the oxidized environment to a reductive milieu. Our data also suggest that kolaviron administration early in infection may foster CD4 response. These data indicate that kolaviron may confer disease-dwindling properties during acute influenza infection via a system-wide protective approach involving multiple targets especially at the early stage of the infection.

Virus genes and host correlates of pathology are markedly reduced during respiratory syncytial and influenza virus co-infection in BALB/c mice

“…Although, caution must be exercised when inferring mouse model studies to humans especially in RSV and IAV infections, this study corroborates findings elsewhere that have described more severe infections during single RSV and IAV infections when compared with cases of viral co-infections (Diaz et al., 2015; Kuchar et al., 2015; Ljubin-sternak et al., 2016). Severe immunopathology and mortality caused by IAV infection has been widely attributed to sustained activation of innate immune responses that supposedly should elicit viral clearance but paradoxically contribute to pathology via a typically defined mechanism known as cytokine storm (Awogbindin et al., 2017; Gruta et al., 2007).…”

Redox control in the pathophysiology of influenza virus infection

“…Kaempferol inhibits the NF-κB and MAPK pathways, leading to an increase in SOD activity, the attenuation of ROS levels, and H9N2induced acute LI [57]. Some ROS scavengers, such as polyphenols, may modulate the NF-κB and MAPK pathways and upregulate GSH biosynthesis through Nrf2 activation [154,172,[190][191][192][193][194]. The immune-regulatory properties of NAC and IV-induced pneumonia are [228] Qi et al [200] related to the inhibition of the p38 MAPK pathway [195].…”

“…Quercetin decreases the production of superoxide in alveolar macrophages during IV infection [ 88 ] and exerts an antiviral activity by inhibiting HA2 during IV infection [ 189 ]. A bioflavonoid isolated from Garcinia kola seeds (kolaviron) exhibits strong anti-IV activity via an antioxidative pathway [ 190 ].…”

Kolaviron ameliorates hepatic and renal dysfunction associated with multiwalled carbon nanotubes in rats

“…anti-inflammatory bioactivities of kolaviron (KV), a natural bioflavonoid derived from the edible but astringent Garcinia kola seed. [19][20][21] Substantial evidence have also shown that KV confers protection against hepatotoxicity and genotoxicity independently induced by potent hepatotoxicants 2-acetyl aminofluorene, aflatoxin B1, dimethyl nitrosamine, and ethanol. [22][23][24][25][26] These toxicants, similar to MWCNTs, 12,13,17 elicit hepatic injury through oxidative stress and pro-inflammatory response whereas the mechanism of protection conferred by KV is largely related to its antioxidant, anti-inflammatory, and antiapoptotic mechanisms.…”

“…Avalanche of reports have demonstrated the antioxidant and anti‐inflammatory bioactivities of kolaviron (KV), a natural bioflavonoid derived from the edible but astringent Garcinia kola seed 19‐21 . Substantial evidence have also shown that KV confers protection against hepatotoxicity and genotoxicity independently induced by potent hepatotoxicants 2‐acetyl aminofluorene, aflatoxin B1, dimethyl nitrosamine, and ethanol 22‐26 .…”