Combinations of 1,8‐cineol and oseltamivir for the treatment of influenza virus A (H3N2) infection in mice

Abstract

It is need for development of new means against influenza virus due to the lack of efficacy of available therapeutic strategies. In previous research, 1,8-cineol exert its inhibition of nuclear factor (NF)-κB, the main regulator of cytokine and chemokine production in influenza, and anti-inflammatory activity. These fact supports and helps establish the hypothesis that 1,8-cineol may have synergism with an antiviral on influenza virus infection. The combined effect of 1,8-cineol with oseltamivir in a mouse type A influenza virus (Victoria/3/75,H3N2) model were examined. We initially tested combinations of 1,8-cineol (30, 60, and 120 mg/kg/day) and oseltamivir (0.1, 0.2, and 0.4 mg/kg/day). In addition, the 0.4 mg/kg/day of oseltamivir combined with 120 mg/kg of 1,8-cineol was selected for further combination studies. Oseltamivir was 30%, 40%, and 60% protective at 0.1, 0.2, and 0.4 mg/kg/d. Combinations of 1,8-cineol (30, 60, and 120 mg/kg/d) and oseltamivir (0.1, 0.2, and 0.4 mg/kg/d) increased the number of survivors and mean survival time (MST) following combination treatment was greater than monotherapy alone. Three dimensional analysis of drug interactions using the MacSynergy method showed a strong synergistic effect of these drug combinations. Survival, MST, lung parameters (lung index, viral titers, and pathology), and cytokines (IL-10, TNF-α, IL-1β, and IFN-γ) expression in lung demonstrated the high effectiveness of the combination. Combined treatment was associated with longer MST and more reduced cytokine levels than oseltamivir alone. These data demonstrate that combinations of 1,8-cineol and oseltamivir have synergistic effect against influenza A virus (H3N2) infection.

Targeting ectromelia virus and TNF/NF-κB or STAT3 signaling for effective treatment of viral pneumonia

“…showed that combined treatment with baricitinib, a selective inhibitor of Janus kinase and remdesivir (an inhibitor of viral, RNA-dependent RNA polymerase) had a greater impact than remdesivir alone in reducing recovery time and improving clinical status of patients hospitalized with COVID-19 ( 59 ). Similarly, different combined-treatment approaches, at least in mouse models, have been reported as promising therapeutic options against influenza pneumonia, namely, hepatocyte growth factor and oseltamivir ( 60 ), clopidogrel (platelet receptor antagonist) and oseltamivir ( 61 ), 1,8-cineol and oseltamivir ( 62 ), L-N G -monomethyl-arginine and oseltamivir ( 63 ), and sphingosine-1-phosphate receptor agonist and oseltamivir ( 64 ). However, translation of these animal studies into clinical practice is limited, as treatments in these studies were commenced either on the day of viral infection or before the onset of clinical signs.…”

Rosmarinus officinalis L. (rosemary) as therapeutic and prophylactic agent

“…Antinociceptive[223]f. Antiviral[224]Rosmanola. Antinociceptive, antidepressant, and anxiolytic[82]b.…”

Essential Oils and COVID-19

“…Additionally, the combination of EOs might be a good strategy for fighting coronaviruses as they are more effective against foodborne pathogens and spoilage bacteria [94,95]. EO ingredients may act synergistically to enhance the effects of other antiviral drugs, or they may relieve COVID-19 symptoms [96], e.g., 1., combinations of eucalyptol and oseltamivir increased the number of survivors, improved lung parameters (viral titers, lung index, and pathology) and reduced cytokines (IL-1β, IL-10, TNF-α) expression in the lung [97], e.g., 2., the combination of Melissa officinalis EO and oseltamivir enhanced the effect of oseltamivir against avian influenza A virus (H9N2) [98], e.g., 3., germacrone plus oseltamivir exhibited additive anti-influenza virus effects in both in vivo and in vitro [99], and, e.g., 4., piperitenone oxide (the main component of Mentha suaveolens EO) plus acyclovir also exhibited synergistic activity against HSV1 [15].…”