Forsythiaside A improves Influenza A virus infection through TLR7 signaling pathway in the lungs of mice

• Published in: BMC complementary and alternative medicine Vol. 22; no. 1; pp. 1 - 164
• Main Authors: Zheng, Xiao, Chen, Ziqi, Shi, Shanshan, Yan, Huijun, Zhou, Junmei, Jiang, Lifang, Wang, Hongli, Hou, Guanghui, Jiang, Zhenyou
• Format: Journal Article
• Language: English
• Published: London BioMed Central Ltd 22.06.2022; BioMed Central; BMC
• Subjects: Antiviral agents; Antiviral drugs; Body weight loss; Bronchitis; Cell culture; Chinese medicine; Disease resistance; Drug resistance; Flow cytometry; Forsythiaside A; Gene expression; Health aspects; Health risks; Helper cells; Herbal medicine; Immune system; Immunology; Immunosuppressive agents; Infections; Infectious diseases; Inflammation; Inflammatory response; Influenza; Influenza A; Influenza A virus; Influenza viruses; Lungs; Lymphocytes T; Medical research; Medicine, Experimental; Mice; mRNA; MyD88 protein; NF-κB protein; Oseltamivir; Pharmaceuticals; Polymerase chain reaction; Public health; RNA; Severe acute respiratory syndrome coronavirus 2; Side effects; Signal transduction; Signaling; TLR7 protein; TLR7−/− mouse; Toll-like receptors; Viral infections; Viruses; Weight loss; China; Japan
• ISSN: 2662-7671; 2662-7671; 1472-6882
• DOI: 10.1186/s12906-022-03644-8

Background Influenza A virus infection due to drug resistance and side effects of the conventional antiviral drugs yet remains a serious public health threat for humans and animals. Forsythiaside A is an effective ingredient isolated from the Chinese herbal medicine forsythia. It has various pharmacological effects and has a good therapeutic effect against a variety of infectious diseases. This study aimed to further explore the immunological mechanism of Forsythiaside A in the treatment of influenza virus-infected mice and its effect on the Toll-like receptor 7 (TLR7) signaling pathway in the lungs of these mice. Methods C57/BL6J mice and TLR7.sup.-/- mice were infected with the FM1 strains (H1N1 and A/FM/1/4) of the Influenza A virus. Each group of experimental mice were divided into the mock, virus, oseltamivir, and Forsythiaside A groups. Weight change, lung index change, and the mRNA and protein expression levels of key factors in the TLR7 signaling pathway were detected. Flow cytometry was used to detect the changes in the Th1/Th2 and Th17/Treg ratios. Results After infection with the Influenza A virus, the weight loss of C57/BL6J mice treated with forsythoside A and oseltamivir decreased, and the pathological tissue sections showed that the inflammatory damage was reduced. The expression levels of the key factors, TLR7, myeloid differentiation factor 88(Myd88), and nuclear factor-kappa B (NF-κB) in the TLR7 signaling pathway were significantly reduced. Flow cytometry showed that Th1/Th2 and Th17/Treg ratios decreased after Forsythiaside A treatment. In the TLR7.sup.-/- mice, there was no significant change after Forsythiaside A treatment in the virus group. Conclusions Forsythiaside A affects the TLR7 signaling pathway in mouse lung immune cells and reduces the inflammatory response caused by the Influenza A virus FM1 strain in mouse lungs. Keywords: Influenza A virus, Forsythiaside A, TLR7.sup.-/- mouse