Forsythoside A Controls Influenza A Virus Infection and Improves the Prognosis by Inhibiting Virus Replication in Mice

Abstract

Abstract:Objective: The objective of this study was to observe the effects of forsythoside A on controlling influenza A virus (IAV) infection and improving the prognosis of IAV infection. Methods: Forty-eight SPF C57BL/6j mice were randomly divided into the following four groups: Group A: normal control group (normal con); Group B: IAV control group (V con); Group C: IAV+ oseltamivir treatment group (V oseltamivir; 0.78 mg/mL, 0.2 mL/mouse/day); Group D: IAV+ forsythoside A treatment group (V FTA; 2 µg/mL, 0.2 mL/mouse/day). Real-time fluorescence quantitative PCR (RT-qPCR) was used to measure mRNA expression of the TLR7, MyD88, TRAF6, IRAK4 and NF-κB p65 mRNA in TLR7 signaling pathway and the virus replication level in lung. Western blot was used to measure TLR7, MyD88 and NF-κB p65 protein. Flow cytometry was used to detect the proportion of the T cell subsets Th1/Th2 and Th17/Treg. Results: The body weight began to decrease after IAV infection, while FTA and oseltamivir could reduce the rate of body weight loss. The pathological damages in the FTA and oseltamivir group were less serious. TLR7, MyD88, TRAF6, IRAK4 and NF-κB p65 mRNA were up-regulated after virus infection (p < 0.01) while down-regulated after oseltamivir and FTA treatment (p < 0.01). The results of TLR7, MyD88 and NF-κB p65 protein consisted with correlative mRNA. Flow cytometry showed the Th1/Th2 differentiated towards Th2, and the Th17/Treg cells differentiated towards Treg after FTA treatment. Conclusions: Our study suggests forsythoside A can control influenza A virus infection and improve the prognosis of IAV infection by inhibiting influenza A virus replication.

Forsythiae Fructus: A Review on its Phytochemistry, Quality Control, Pharmacology and Pharmacokinetics

“…Phenylethanoid glycosides are the major bioactive constituents of Forsythiae Fructus with verified anti-inflammatory, antioxidant, antibacterial and antiviral effects [ 27 , 28 , 76 , 77 ]. Since forsythoside A ( 1 ) was reported by Endo et al [ 20 ] in 1984, fifty-one phenylethanoid glycosides have been isolated from Forsythiae Fructus and their structures were shown in Figure 1 .…”

“…Four compounds from Forsythia Fructus , namely forsythoside A ( 1 ), calceolarioside B ( 33 ), phillyrin ( 60 ) and rengynic acid ( 108 ), also demonstrated significant antiviral activity. In vivo, forsythoside A ( 1 ) at 20 ug/kg was able to control H1N1 infection and relieved the symptoms by inhibiting expression of Toll-like receptor 7 (TLR7), MyD88, tumor necrosis factor receptor-associated factor 6 (TRAF6), interleukin-4 receptor-associated kinase (IRAK4) and NF-kB p65 mRNA and H1N1 replication in C57BL/6j mice [ 77 ]. Phillyrin ( 60 ) inhibited H1N1 expresstion by down-regulating the gene of the H1N1 nucleoprotein in vitro and in vivo [ 118 , 119 ].…”

Exploration of the mechanisms of Ge Gen Decoction against influenza A virus infection

“…Lung and peripheral blood were harvested for further analysis. Based on previous reports, the viral load in the lung tissue was determined by RT-PCR assay [21] .…”

Effect of Forsythiaside A on the RLRs Signaling Pathway in the Lungs of Mice Infected with the Influenza A Virus FM1 Strain

“…In addition, FTA acts as an immunomodulatory agent by regulating different types of cytokines and is considered a potential therapeutic agent [9,10]. In fact, FTA was reported to show a significant therapeutic effect against influenza A virus infection in mice [11]. The molecular structure is shown in Figure 1.…”