Flavonoids and Polysaccharides from Houttuynia Cordata Synergistically Alleviated H1N1-Induced Viral Pneumonia in Mice Via Multimodal Regulation of Pulmonary and Intestinal Homeostasis

Ethnopharmacological relevance: Houttuynia cordata Thunb. (HC, Saururaceae family) is a classical Traditional Chinese Medicine used to treat pneumonia clinically. The total flavonoids (HCF) and polysaccharides (HCP) are key medicinal components of H. cordata involved in its beneficial effect on viral pneumonia.Aim of the studyThe purpose of the study is to investigate the synergistic or complementary effects of combination of HCF and HCP on viral pneumonia as well as the mechanisms underlying.Materials and methods: HCF or HCP were administrated separately, or combined in different proportions on influenza virus H1N1 – infected mice. The survival and lung weight of mice were recorded. The synergistic effect on HCF and HCP combination was calculated by Chou-Talalay method. H&E staining was performed to detect lung histomorphology. Western blots, immunohistochemistry and enzyme linked immunosorbent assay were done to analyze the representative protein expression in lung and intestine tissue. AB - PAS staining on intestine tissue sections was performed to evaluate the histopathology of intestine. Bacterial genomic DNA was extracted and sequenced for gut microbiota analysis.Results: In H1N1 lethally infected mice, the combined administration of HCF and HCP significantly increased the survival rate and prolonged the life span of mice, compared with mono-drug therapy. The viral pneumonia was remarkably improved by combination treatment which was reflected by lower lung index, more intact lung morphology, and less inflammatory cells and mediates. Furthermore, the combination of HCF and HCP regulated intestinal microbiota, significantly reduced the proportion of pathogenic Proteobacteria and the secretion of proinflammatory cytokine in gut. The combined HCF and HCP showed synergistic effect on reducing lung and intestine injury.The complementary interaction was also found in HCF and HCP combined therapy, as HCF provided the significant antiviral activity and HCP markedly improved intestinal physical barrier and increased the protein expression involving removal of edema.Conclusions: Our findings indicated that combination of HCF and HCP from H. cordata synergistically alleviated H1N1-induced viral pneumonia in mice via multimodal regulation of both pulmonary and intestinal homeostasis, which might imply novel therapeutic strategy for treating viral pneumonia.