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

Abstract

Forsythiaside A, a phenylethanoid glycoside monomer extracted from Forsythia suspensa, shows anti-inflammatory, anti-infective, anti-oxidative, and antiviral pharmacological effects. The precise mechanism underlying the antiviral action of forsythiaside A is not completely clear. Therefore, in this study, we aimed to determine whether the anti-influenza action of forsythiaside A occurs via the retinoic acid-inducible gene-I–like receptors (RLRs) signaling pathway in the lung immune cells. Forsythiaside A was used to treat C57BL/6J mice and MAVS−/− mice infected with mouse-adapted influenza A virus FM1 (H1N1, A/FM1/1/47 strain), and the physical parameters (body weight and lung index) and the expression of key factors in the RLRs/NF-κB signaling pathway were evaluated. At the same time, the level of virus replication and the ratio of Th1/Th2 and Th17/Treg of T cell subsets were measured. Compared with the untreated group, the weight loss in the forsythiaside A group in the C57BL/6J mice decreased, and the histopathological sections showed less inflammatory damage after the infection with the influenza A virus FM1 strain. The gene and protein expression of retinoic acid-inducible gene-I (RIG-I), MAVS, and NF-κB were significantly decreased in the forsythiaside A group. Flow cytometry showed that Th1/Th2 and Th17/Treg differentiated into Th2 cells and Treg cells, respectively, after treatment with forsythiaside A. In conclusion, forsythiaside A reduces the inflammatory response caused by influenza A virus FM1 strain in mouse lungs by affecting the RLRs signaling pathway in the mouse lung immune cells.

Forsythiaside A inhibits hydrogen peroxide-induced inflammation, oxidative stress, and apoptosis of cardiomyocytes

“…Protein expression of p-p65 was upregulated in H2O2-stimulated H9c2 cells suggesting that the NF-κB pathway was activated. Forsythiaside A was shown to decrease NF-κB expression to alleviate virusinduced lung tissue damage [15]. In this study, forsythiaside A reduced p-p65 expression in H2O2-induced H9c2 cells.…”

Toxicity as prime selection criterion among SARS-active herbal medications

“…The aqueous extract of the fruit of Forsythia is widely used in traditional medicines against many frequently occurring disorders including inflammation, pain, fever, nausea, vomiting and abscess, leading to a rich treasure of information on its use ( Wang et al, 2018 ). Forsythoside A ( Law et al, 2017 ; Zheng et al, 2019 ) and labdane diterpenoids ( Xiang et al, 2020 ; Zhao et al, 2020 ) isolated from the fruits of Forsythia suspensa showed antiviral activities and, as already stated in the Introduction, Forsythia is one of the herbal medicines, which were successfully used for the therapy of the SARS-CoV infected patients in the 2002/2003 SARS epidemic ( Liu et al, 2006 ; 2012a , 2012b ; Wang et al, 2014 ; Luo et al, 2020 ).…”

Pharmacologic Activities of Plant-Derived Natural Products on Respiratory Diseases and Inflammations

“…The number of neutrophils as mediators of inflammation and macrophages was reduced which typically reduced inflammations in the lungs of cigarette and smoke-induced mice [ 154 ]. It was reported to act as an immunomodulatory agent which showed an increment in anti-inflammatory cytokines after treatment and restrained the activation of T cell immune response [ 172 ]. Forsythiaside A could be developed as a possible therapeutic candidate against respiratory complications.…”