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Andrographolide as an anti-H1N1 drug and the mechanism related to retinoic acid-inducible gene-I-like receptors signaling pathway #MMPMID24972581
Yu B; Dai CQ; Jiang ZY; Li EQ; Chen C; Wu XL; Chen J; Liu Q; Zhao CL; He JX; Ju DH; Chen XY
Chin J Integr Med 2014[Jul]; 20 (7): 540-5 PMID24972581show ga
OBJECTIVE: To observe the anti-virus effects of andrographolide (AD) on the retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) signaling pathway when immunological cells were infected with H1N1. METHODS: Leukomonocyte was obtained from umbilical cord blood by Ficoll density gradient centrifugation, and immunological cells were harvested after cytokines stimulation. Virus infected cell model was established by H1N1 co-cultured with normal human bronchial epithelial cell line (16HBE). The optimal concentration of AD was defined by methyl-thiazolyl-tetrazolium (MTT) assay. After the virus infected cell model was established, AD was added into the medium as a treatment intervention. After 24-h co-culture, cell supernatant was collected for interferon gamma (IFN-gamma) and interleukin-4 (IL-4) enzyme-linked immunosorbent assay (ELISA) detection while immunological cells for real-time polymerase chain reaction (RT-PCR). RESULTS: The optimal concentration of AD for anti-virus effect was 250 mug/mL. IL-4 and IFN-gamma in the supernatant and mRNA levels in RLRs pathway increased when cells was infected by virus, RIG-I, IFN-beta promoter stimulator-1 (IPS-1), interferon regulatory factor (IRF)-7, IRF-3 and nuclear transcription factor kappaB (NF-kappaB) mRNA levels increased significantly (P<0.05). When AD was added into co-culture medium, the levels of IL-4 and IFN-gamma were lower than those in the non-interference groups and the mRNA expression levels decreased, RIG-I, IPS-1, IRF-7, IRF-3 and NF-kappaB decreased significantly in each group with significant statistic differences (P<0.05). CONCLUSIONS: The RLRs mediated viral recognition provided a potential molecular target for acute viral infections and andrographolide could ameliorate H1N1 virus-induced cell mortality. And the antiviral effects might be related to its inhibition of viral-induced activation of the RLRs signaling pathway.
|Adaptor Proteins, Signal Transducing/genetics/metabolism[MESH]