OBJECTIVE To study the possible effects and mechanism of Jinxin oral liquid and its main ingredient baicalin on Respiratory syncytial virus (RSV)-induced abnormal cardiolipin metabolism.
METHODS BALB/c mice were randomly divided into control group, RSV group and Jinxin oral liquid treatment group. Mice were nasally administrated of RSV suspension to establish RSV infection model at the first 3 days. Then Jinxin oral liquid 27. 6 g·kg-1·d-1 was administrated intragastrically for the next 3 days from the afternoon of the third day. Raw264.7 cells were infected by RSV to establish an in vitro infection model and baicalin (100 mg·kg-1·d-1) was given for intervention. The changes of cardiolipin metabolism profiles in mice lung tissue and Raw264. 7 cells were detected by chromatography-mass spectrometry. Transcriptional mRNA levels of RSV surface proteins RSV-F and RSV-G, inflammatory cytokines IL-6, IL-1β and Tnf-α, cardiolipin metabolic enzymes Tafazzin (TAZ), Cardiolipin Synthase 1 (Crls1), Phospholipid Scramblase 3 (PLSCR3) and autophagy-related protein p62 were detected by qPCR. The protein level of p62 was detected by Western blot. Molecular docking was used to detect the binding ability of p62 to CL14∶0-16∶1-16∶1-18∶2.
RESULTS The expression of IL-6, IL-1β, and Tnf-α mRNA increased in RSV-infected mice and cell models (P < 0.05, P < 0.01, P < 0.001). Jinxin oral liquid and baicalin plays a certain restoration effect. The cardiolipin metabolism profile changes after RSV infection, and Jinxin oral liquid and baicalin can play a certain regulatory role. The expression of Crls1 and TAZ mRNA in the lung tissue of mice in the model group was significantly up-regulated (P < 0. 01), after administration of Jinxin oral liquid, the expression of Crls1 and TAZ mRNA was significantly reduced (P < 0. 01); the expression of Crls1 mRNA in the cell model group was significantly increased (P < 0. 001), and after baicalin intervention, the expression of Crls1 mRNA was significantly reduced (P < 0.000 1). The expression of p62 protein in the lung tissue of RSV-infected mice was significantly reduced (P < 0.001), and the expression of p62 protein was significantly increased after administration of Jinxin oral liquid (P < 0.01). The p62 protein expression in the Raw264.7 cell model group increased significantly (P < 0.05), and the p62 protein level further increased significantly after administration of baicalin (P < 0.000 1). Molecular docking results showed that cardiolipin CL14∶0-16∶1-16∶1-18∶2 can threshold-bind with the UBA structure of p62.
CONCLUSION Jinxin oral liquid and baicalin can improve RSV-induced cardiolipin metabolism disorder, regulate mitochondrial function, and thus exert anti-RSV infection effects.
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