Elucidating the material basis and mechanism of Shegan Mahuang decoction in inhibiting influenza virus pneumonia based on UHPLC-HRMS, network pharmacology and experimental verification.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Shegan Mahuang Decoction (SMD), a traditional Chinese medicinal prescription outlined in "Jin Gui Yao Lue". For approximately two thousand years, it has been widely used to treat asthma and flu-like symptoms in China and Japan for around twenty centuries. While the efficacy is confirmed, its pharmacological mechanism remains unclear. AIM OF THE STUDY: This study aimed to systematically evaluate the protective effects of SMD against influenza A virus (IAV)-induced pneumonia and explore its action mechanism. MATERIALS AND METHODS: Material basis and absorbed components of SMD were analyzed using UHPLC-HRMS. Integrating absorbed components and network pharmacology to predict its potential for treating influenza and its mechanism of action. By using the IAV pneumonia model, the abilities of SMD to suppress pathogenic-evil and pneumonia were confirmed using MDCK cells and BALB/c mice. RESULTS: UHPLC-HRMS identified 497 components in SMD, of which 125 were absorbed into the bloodstream of mice. Network pharmacology analysis based on absorbed components indicates SMD's anti-influenza effects through multiple biological processes associated with infection and immunity. SMD can inhibit viral proliferation in vitro and protect MDCK cells. It increased survival in infected mice from 8 to over 12 days. In the mice with IAV pneumonia, SMD significantly alleviated pathological damage, reduced viral proteins and mucins in lung tissue. It also regulates cytokines including TNF-α, IL-1β, and IL-6, and inhibited the activation of TLR/TAK/NF-κB and MEK/ERK signaling pathways. CONCLUSION: This study has confirmed that SMD can alleviate the hyper-inflammatory response in the host induced by IAV. It suggests that SMD can treat pneumonia by inhibiting pathogenic-evil factors.