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Anti-influenza effect and action mechanisms of the chemical constituent gallocatechin-7-gallate from Pithecellobium clypearia Benth

  
@article{APS9891,
	author = {Chao Li and Lv-jie Xu and Wen-wen Lian and Xiao-cong Pang and Hao Jia and Ai-lin Liu and Guan-hua Du},
	title = {Anti-influenza effect and action mechanisms of the chemical constituent gallocatechin-7-gallate from  Pithecellobium clypearia  Benth},
	journal = {Acta Pharmacologica Sinica},
	volume = {39},
	number = {12},
	year = {2018},
	keywords = {},
	abstract = {Host cdc2-like kinase 1 (CLK1) is responsible for the alternative splicing of the influenza virus M2 gene during influenza virus infection and replication that has been recognized as a potential anti-influenza virus target. In this study, we showed that gallocatechin-7-gallate (J10688), a novel CLK1 inhibitor isolated from Pithecellobium clypearia Benth, exerted potent anti-influenza virus activity in vivo and in vitro. ICR mice were intranasally infected with a lethal dose of H1N1. Administration of J10688 (30 mg·kg−1·d−1, iv, for 5 days) significantly increased the survival rate of the H1N1-infected mice to 91.67% and prolong their mean survival time from 5.83 ± 1.74 days to 13.66 ± 1.15 days. J10688 administration also slowed down body weight loss, significantly alleviated influenza-induced acute lung injury, reduced lung virus titer, elevated the spleen and thymus indexes, and enhanced the immunological function. We further explored its anti-influenza mechanisms in the H1N1-infected A549 cells: as a novel CLK1 inhibitor, J10688 (3, 10, 30 μmol/L) dose-dependently impaired synthesis of the viral proteins NP and M2, and significantly downregulated the phosphorylation of splicing factors SF2/ASF and SC35, which regulate virus M2 gene alternative splicing. As a novel CLK1 inhibitor with potent anti-influenza activity in vitro and in vivo, J10688 could be a promising antiviral drug for the therapy of influenza A virus infection.},
	url = {http://www.chinaphar.com/article/view/9891}
}