Effect of Shufeng Jiedu Capsules on Improving Lung Inflammation in Mice Infected with Human Coronavirus 229E by Regulating TLR4/TRIF/TBK1 Signaling Pathway
ObjectiveTo study the anti-inflammatory and immunomodulatory effects of Shufeng Jiedu capsules in a mouse model infected with human coronavirus 229E (HCoV-229E).MethodsForty-eight BALB/c mice were randomly divided into a normal group, a model group, a chloroquine positive group, and high-dose, medium-dose, and low-dose groups of Shufeng Jiedu capsules, with eight mice in each group. The coronavirus infection model was established by intranasal infection with the HCoV-229E virus solution. On the fourth day after infection, the mice were killed by cervical dislocation. The pathological changes in the lung were evaluated by weighing the wet weight of the lung and calculating the lung index. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot (WB) techniques were used to detect the expression levels of key genes and proteins such as Toll-like receptor 4 (TLR4), Toll/interleukin-1 receptor (TIR)-domain-containing adapter inducing interferon-β (TRIF), tumor necrosis factor receptor-associated factor 6 (TRAF6), TANK-binding kinase 1 (TBK1), phospho-TANK-binding kinase 1 (p-TBK1), interferon regulatory factor 3 (IRF3), and phospho-interferon regulatory factor 3 (p-IRF3) in lung tissue.ResultsCompared with that in the normal group, the lung index of the mice in the model group was significantly increased (P<0.01). There was a large amount of inflammatory exudation in the pulmonary interstitium, and the expression of TLR4, TRIF, TRAF6, TBK1, p-TBK1, IRF3, and p-IRF3 proteins was significantly increased (P<0.01), indicating that HCoV-229E caused severe pulmonary inflammation. Compared with the model group, Shufeng Jiedu capsules at each dose significantly reduced the lung index of mice (P<0.01), among which the lung index inhibition rate of the high-dose and medium-dose groups was 78.18% and 79.27%. At the same time, Real-time PCR and WB results showed that the medium-dose Shufeng Jiedu capsules significantly reduced the gene and protein expression levels of TLR4, TRIF, TRAF6, TBK1, p-TBK1, and p-IRF3 (P<0.05).ConclusionShufeng Jiedu capsules can alleviate lung inflammation and tissue injury caused by coronavirus infection by inhibiting the excessive activation of the TLR4/TRIF/TBK1 signaling pathway.