Intestinal microbiota analysis and network pharmacology reveal the mechanism by which Lianhua Qingwen capsule improves the immune function of mice infected with influenza A virus

Abstract

ObjectiveLianhua Qingwen capsule (LHQW) can attenuate lung injury caused by influenza virus infection. However, it is unclear whether the intestinal microbiota plays a role in LHQW activity in ameliorating viral infectious pneumonia. This study aimed to investigate the role of intestinal microbiota in LHQW activity in ameliorating viral infectious pneumonia and its possible mechanisms.Research design and methodsA mouse model of influenza A viral pneumonia was established by intranasal administration in BALB/c mice. Detection of influenza virus in the lungs, pathological examination of the lungs and small intestine, and biochemical detection of inflammatory indices were performed. The effects of LHQW on intestinal microbiota were evaluated by 16S rRNA gene sequencing. The key components and targets of LHQW were screened via network pharmacology and verified through molecular docking, molecular dynamics simulation, and free binding energy calculations.ResultsBody weight decreased, inflammatory factor levels were disturbed, and the lung and intestinal mucosal barriers were significantly injured in the infected group. The alpha diversity of the intestinal microbiota decreased, and the abundance of Bacteroidetes, Muribaculaceae_unclassified, and Streptococcus decreased significantly. LHQW treatment reduced the viral load in the lungs, rescued body weight and survival, alleviated lung and intestinal mucosal barrier injury, reversed the reduction in the intestinal microbiota alpha diversity, and significantly increased the abundance of Bacteroidetes and Muribaculaceae. Network pharmacological analysis showed that six active herbal medicinal compounds from LHQW could regulate the intestinal microbiota and inhibit the immune-inflammatory response through the Toll-like receptor (TLR) and nuclear factor-κB (NF-κB) signalling pathways in the lungs.ConclusionThese results suggest that LHQW is effective for treating influenza A virus infectious pneumonia, and the mechanism is associated with the regulation of the TLR4/NF-κB signalling pathway in the lungs by restoring intestinal microbiota and repairing the intestinal wall.

“Three medicines and three formulas” in COVID-19: From bench to bedside

“…LHQW can be used to treat COVID-19 by targeting ACE2 and 3CL pro , achieving immunoregulation via targeting the immune responses to SARS-CoV-2, providing anti-inflammation activity by targeting cytokines, and thus demonstrating anti-viral potency against SARS-CoV-2 [73] . The results of intestinal microbiota analysis and network pharmacology have revealed that LHQW can be used to effectively treat influenza A virus–infected pneumonia, the mechanism of which may be related to the regulation of the lung TLR4/NF-κB signaling pathway by restoring intestinal flora and repairing the intestinal wall [74] .…”