Abstract

Influenza B virus (IBV) is one of the main pathogens of the annual influenza epidemic, and the disease burden is significant, especially among children and young teenagers. In this study, the antiviral and anti-inflammatory effects of a traditional Chinese medicine prescription, the Lianhua-Qingwen capsule, were evaluated. Our results showed that Lianhua-Qingwen capsule can inhibit both Victoria and Yamagata lineages, and the 50% inhibitive concentrations ranged from 0.228 ± 0.150 to 0.754 ± 0.161 mg/mL. The time course results demonstrated that IBV yields were reduced with treatment at 0–4 h after infection, and the mechanistic research verified that Lianhua-Qingwen capsule has hemagglutination inhibition activity against B/Guangzhou/0215/2012 but not A/California/04/2009. In addition to antiviral activity, Lianhua-Qingwen capsule can also inhibit excessive expression of RANTES, IL-6, IL-8, IP-10, TNF-α, MCP-1, MIP-1β, and IFN-λ at the mRNA level and prevent a severe inflammatory response. The in vivo results confirmed that orally administered Lianhua-Qingwen capsule (100–400 mg/kg/day) does not reduce IBV-induced lung viral load and mortality in mice. However, the pathological change in lungs was alleviated, and there were fewer inflammatory cells in the lungs of Lianhua-Qingwen capsule treated mice than those in controls. Further research confirmed that the combination treatment of 200 mg/kg/day of Lianhua-Qingwen capsule with 2 mg/kg/day of oseltamivir significantly reduced IBV infection over the individual administration of either alone in vivo. Our findings prove that Lianhua-Qingwen capsule could be used as an assistant medicine to enhance the effect of oseltamivir against influenza B virus infection.

Highlights

  • Influenza B virus (IBV), one of the main pathogens of annual influ enza epidemics, is divided into two genetically and antigenically distinct lineages, B/Victoria/2/1987-like (Victoria) and B/Yamagata/16/1988-like (Yamagata)

  • We tested the antiviral activity of LianhuaQingwen capsule (LQ) against five stains of influenza B viruses: B/Lee/40, three of Victoria-like virus, and one of Yamagata-like virus. e results (Table 1) showed that LQ exhibited an inhibitory effect on five IBV strains with 50% inhibitive concentrations (IC50) ranging from 0.228 ± 0.150 to 0.754 ± 0.161 mg/mL, and the selective index (SI) [18] ranged from 5.3 to 17.6. e inhibitory effect of LQ against the strains isolated in 2016 was more potent than that on the strains isolated before 2012

  • In posttreatment model, the time course results (Figure 1(b)) showed that IBV yield was reduced with treatment with 0.6 mg/mL of LQ at 0–4 h after infection, but treatment was not effective in reducing yield at more than 6 h. is demonstrated that LQ inhibits the early stages of viral cycle of IBV

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Summary

Introduction

Influenza B virus (IBV), one of the main pathogens of annual influ enza epidemics, is divided into two genetically and antigenically distinct lineages, B/Victoria/2/1987-like (Victoria) and B/Yamagata/16/1988-like (Yamagata). Both lineages of IBVs circulate or cocirculate globally with the H1N1 or H3N2 subtype of influenza A viruses (IAVs) in annual seasonal epidemics. Recent clinical studies suggest that oseltamivir is less effective in treating IBV than IAV [8, 9]. In clinical studies in Japan, when more than 100 children with influenza B or influenza A (H3N2) were administered oseltamivir, the results showed that oseltamivir was less effective for influenza B than influenza A in reducing the time the virus lasted or duration of fever [10,11,12]

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