Baicalin Downregulates RLRs Signaling Pathway to Control Influenza A Virus Infection and Improve the Prognosis

Abstract

The objective of this study is to investigate the effects of baicalin on controlling the pulmonary infection and improving the prognosis in influenza A virus (IAV) infection. PCR and western blot were used to measure the changes of some key factors in RLRs signaling pathway. MSD electrochemiluminescence was used to measure the expression of pulmonary inflammatory cytokines including IFN-γ, TNF-α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, and KC/GRO. Flow cytometry was used to detect the proportion of Th1, Th2, Th17, and Treg. The results showed that IAV infection led to low body weight and high viral load and high expression of RIG-I, IRF3, IRF7, and NF-κB mRNA, as well as RIG-I and NF-κB p65 protein. However, baicalin reduced the rate of body weight loss, inhibited virus replication, and downregulated the key factors of the RLRs signaling pathway. Besides, baicalin reduced the high expression inflammatory cytokines in lung and decreased the ratios of Th1/Th2 and Th17/Treg to arouse a brief but not overviolent inflammatory response. Therefore, baicalin activated a balanced host inflammatory response to limit immunopathologic injury, which was helpful to the improvement of clinical and survival outcomes.

Antiviral effect of baicalin on Marek’s disease virus in CEF cells

“…In addition, the expression levels of pro-in ammatory factors IL-1β and IL-6 were slightly decreased in MDV infected CEF cells treated with baicalin, but the difference was not signi cant. This is inconsistent with previous study that baicalin controls in uenza A virus infection by down-regulating the RLRs signaling pathway [16]. This difference may be related to the different antiviral mechanisms of baicalin in different cells.…”

Antiviral effect of baicalin on Marek’s disease virus in CEF cells

“…In addition, the expression levels of pro-inflammatory factors IL-1β and IL-6 were slightly decreased in MDV infected CEF cells treated with baicalin, but the difference was not significant. This is inconsistent with previous study that baicalin controls influenza A virus infection by down-regulating the RIG-I-like receptors signaling pathway [20]. This difference may be related to the different antiviral mechanisms of baicalin in different cells.…”

Natural product derived phytochemicals in managing acute lung injury by multiple mechanisms

“… Compounds Structure In vitro/in vivo Model (effective dose) Cells (effective concentration) Related pharmacological indicators Related molecular mechanisms Refs. Luteolin 1 LPS/CLP (1 mg/kg) RAW 264.7 (20 μM) MPO↓ TNF-α↓ IL1-β↓ IL-6↓ MDA↓ SOD↑ CAT↑ GSH↑ COX-2↓ iNOS↓ ICAM-1↓ HMGB1↓ Inhibition of PI3K/Akt-mediated NF-κB and MAPK signaling pathways Activation of ERK1/2- and Ca 2+ -dependent HO-1 induction [ [65] , [66] , [67] , [68] , [69] , [70] , [71] , [72] , [73] ] Baicalein 2 CLP/I/R (10 mg/kg) MPMs (2.5 μM) MPO↓ TNF-α↓ IL1-β↓ IL-6↓ ICAM-1↓ IL-12↓ MCP-1↓ Inhibition of TLR4-MD2- MAPKs/ NF-κB signaling pathways Upregulation of Nrf2/HO-1 signaling pathway Inhibition of Bax/Bcl-2-mediated apoptosis [ [74] , [75] , [76] ] Baicalin 3 LPS/ Burn/RSV/IAV/APEC/ SiO 2 /Air embolism/Paraquat /Cigarette smoke/Pancreas (20 mg/kg) MPO↓ TNF-α↓ IL1-β↓ IL-6↓ IL-8↓IL-23↓ MDA↓ SOD↑ CAT↑ IL-18↓ TGF-β↓ HMGB1↓ Activation of Nrf2/HO-1 signaling pathway Inhibition of NLRP3 inflammasome Inhibition of the crosstalk between CX3CL1-CX3CR1 axis and NF-κB pathway Up-regulation of autophagy Inhibition of PI3K/AKT/ NF-κB signaling pathway [ [77] , [78] , [79] , [80] , [81] , [82] , [83] , [84] , [85] , [86] , [87] ] Tanshinone IIA 4 LPS/Paraquat/Blast/Pancreatitis /Seawater...…”

“…Baicalin 3 , also one of the principal constituents extracted from Chinese medicinal plant Scutellaria baicalensis Georgi, can alleviate lung impairment as shown by attenuated MPO activity, lung edema and lung histopathologic changes in ALI models induced by various stimuli such as LPS, burn, respiratory syncytial virus (RSV), Influenza A virus (IAV), SiO 2 , air embolism, paraquat, cigarette smoke or pancreatitis [ [77] , [78] , [79] , [80] , [81] , [82] , [83] , [84] , [85] ]. Baicalin could alleviate pulmonary inflammation through down-regulating expression of pro-inflammatory cytokines TNF-a, IL-1β, IL-6, IL-8, IL-18, IL-23 and MMP9 [ 77 ].…”