ABSTRACT
Background and aim: Qingfei Jiedu Granules (QFJD) are a new Traditional Chinese Medicine (TCM) which has been clinically used against coronavirus pneumonia in China. In this study, the therapeutic effect and the underlying mechanisms of QFJD against influenza were investigated. Experimental procedure: Pneumonia mice were induced by influenza A virus. Survival rate, weight loss, lung index and lung pathology were measured to evaluate the therapeutic effect of QFJD. The expression of inflammatory factors and lymphocytes was used to assess anti-inflammatory and immunomodulatory effect of QFJD. Gut microbiome analysis was performed to decipher the potential effect of QFJD on intestinal microbiota. Metabolomics approach was conducted to explore the overall metabolic regulation of QFJD. Result and conclusion: QFJD shows a significant therapeutic effect on the treatment of influenza and the expression of many pro-inflammatory cytokines were obviously inhibited. QFJD also markedly modulates the level of T and B lymphocytes. The high-dose QFJD has shown similar therapeutic efficiency compared to positive drugs. QFJD profoundly enriched Verrucomicrobia and maintained the balance between Bacteroides and Firmicutes. QFJD associated with 12 signaling pathways in metabolomics study, 9 of which were the same as the model group and were closely related to citrate cycle and amino acid metabolism.To sum up, QFJD is a novel and promising drug against influenza. It can regulate inflammation, immunity, metabolism, and gut microbiota to fight influenza. Verrucomicrobia shows great potential to improve influenza infection and may be an important target.
ABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Coronavirus and influenza virus infection seriously threaten human health. Cangma Huadu Granules (CMHD) is an in-hospital preparation composed of eight traditional Chinese medicines (TCM), which has been clinically used against COVID-19 in China and may be a promising candidate for the treatment of influenza. However, the role of its treatment urgently needs to be studied. AIM OF THE STUDY: To evaluate the therapeutic effects of CMHD on pneumonia induced by coronavirus (HCoV-229E) and influenza A virus (H1N1/FM1) in mice and explore its mechanism of anti-infection. MATERIALS AND METHODS: Mice were infected with HCoV-229E or H1N1/FM1 virus through the nasal cavity. CMHD (12.1, 6.05 and 3.03 g/kg/d) or the positive control drugs were administered intragastrically. The lung index and histopathological changes were used to evaluate the therapeutic effect of CMHD. The expression of TNF-α, IL-1ß, IL-6 and IL-4 in Serum and the proportion of CD4+ and CD8+ T lymphocytes in peripheral blood were detected to evaluate the anti-inflammatory and immune regulation effects of CMHD, respectively. Furthermore, the levels of p-NF-κBp65/ NF-κB p65, which was the key targets of the NF-κB pathway was analyzed. RESULTS: In HCoV-229E-induced pneumonia, the lung index was markedly reduced, and lung pathology was improved in mice that treated with CMHD (12.1, 6.05 g/kg/d). Meanwhile, the expression of TNF-α, IL-6 were obviously inhibited, but the expression of IL-4 was significantly increased in CMHD groups. Compared with the model group, CMHD could also markedly upregulate the level of CD4+ and CD8+. Furthermore, CMHD has a markedly effect on inhibit the expression of p-NF-κB p65/NF-κB p65 in the lung. In H1N1-induced pneumonia, the lung index of mice in the CMHD (12.1 g/kg/d) treatment group was lower than that in the model group, and less inflammatory infiltration could be seen in the lung pathological. Moreover, CMHD could also obviously decrease the expression of TNF-α, IL-1ß, IL-6, but significantly increase the expression of IL-4. Except for that, CMHD could also markedly downregulate the level of CD4+ and upregulate the level of CD8+ compared with the model group. In addition, CMHD has a markedly effect on inhibit the expression of p-NF-κB p65/NF-κB p65 in the lung. CONCLUSION: CMHD can significantly combats viral infections caused by HCoV-229E and H1N1, and the mechanism may be related to its multiple functions of anti-inflammatory, immunity regulating and inhibiting NF-κB signal transduction pathway.