Mechanism of Jinzhen Oral Liquid against influenza-induced lung injury based on metabonomics and gut microbiome

Abstract

Ethnopharmacological relevance: Jinzhen Oral Liquid (JZOL) is a traditional Chinese patent medicine and widely used clinically, which consists of eight herbs including Bovis Calculus Atifactus, Fritillariae Ussuriensis Bulbus (Fritillaria ussuriensis Maxim.), Caprae Hircus Cornu, Rhei Radix et Rhizoma (Rheum palmatum L.), Scutellariae Radix (Scutellaria baicalensis Georgi), Glycyrrhizae Radix et Rhizoma (Glycyrrhiza uralensis Fisch. ex DC.), Chloriti Lapis, and Gypsum Fibrosum (Their ratio is 9.45 : 47.25: 94.5 : 31.5: 15.75 : 31.5: 15.75 : 23.62). A large number of clinical studies have proved that JZOL has a good antiviral effect and can treat lung injury, pneumonia, and bronchitis caused by a variety of viral infections.

Aim of the study: Influenza infection frequently exhibit dysregulation of gut microbiota and host metabolomes, but the mechanism of JZOL is still unclear and needs to be further explored. Here, after influenza virus infection induced lung injury, the regulation roles of JZOL in metabolic and gut microbiota balances are investigated to comprehensively elucidate its therapeutic mechanism.

Materials and methods: A mouse model of lung injury was replicated via intranasal instillation of influenza A (H1N1). The efficacy of JZOL was evaluated by pathological sections, lung index, the levels of TNF-α and IFN-γ, and viral load in lung tissue. Its modulation of endogenous metabolites and gut microbiota was assessed using plasma metabolomic technique and 16S rRNA high-throughput sequencing technique.

Results: JZOL not only significantly relieved lung inflammation and edema in influenza mice, but also alleviated the disturbance of endogenous metabolites and the imbalance of gut microbiota mainly by regulating glycerophospholipid and fatty acid metabolism and Lactobacillus. The anti-influenza effects of JZOL were gut microbiota dependent, as demonstrated by antibiotic treatment. The altered metabolites were significantly correlated with Lactobacillus and pharmacodynamic indicators, further confirming the reliability of these results.

Conclusions: JZOL attenuates H1N1 influenza infection induced lung injury by regulating lipid metabolism via the modulation of Lactobacillus. The results support the clinical application of JZOL, and are useful to further understand the mechanism of TCM in the treatment of influenza.

Keywords: Gut microbiome; Influenza-induced lung injury; Jinzhen oral liquid; Lactobacillus; Lipid metabolism; Metabolomics.