Indirubin, a bisindole alkaloid from Isatis indigotica, reduces H1N1 susceptibility in stressed mice by regulating MAVS signaling
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Chong Jie1,2, Zhuo Luo1,2, Huan Chen1,2, Min Wang3, Chang Yan1,2, Zhong-Fu Mao1,2, Gao-Keng Xiao2, Hiroshi Kurihara1,2, Yi-Fang Li1,2 and Rong-Rong He1,2
1Anti-Stress and Health Research Center, College of Pharmacy, Jinan University, Guangzhou 510632, China
2Institute of Traditional Chinese Medicine & Natural Products, Jinan University, Guangzhou 510632, China
3Department of Pharmacy, Hainan General Hospital, Hainan 570311, China
Rong-Rong He, email: firstname.lastname@example.org
Yi-Fang Li, email: email@example.com
Hiroshi Kurihara, email: Kurihara_hiroshi@163.com
Keywords: indirubin; influenza virus; virus susceptibility; MAVS; STING
Received: February 25, 2017 Accepted: July 18, 2017 Published: November 09, 2017
Isatis indigotica has a long history in treating virus infection and related symptoms in China. Nevertheless, its antivirus evidence in animal studies is not satisfactory, which might be due to the lack of appropriate animal model. Previously, we had utilized restraint stress to establish mouse H1N1 susceptibility model which was helpful in evaluating the anti-virus effect of medicines targeting host factors, such as type I interferon production. In this study, this model was employed to investigate the effect and mechanism of indirubin, a natural bisindole alkaloid from Isatis indigotica, on influenza A virus susceptibility. In the in vitro study, the stress hormone corticosterone was used to simulate restraint stress. Our results demonstrated that indirubin decreased the susceptibility to influenza virus with lowered mortality and alleviated lung damage in restraint-stressed mice model. Moreover, indirubin promoted the expression of interferon-β and interferon inducible transmembrane 3. In addition, indirubin maintained the morphology and function of mitochondria following influenza A virus infection. Further study revealed that indirubin promoted interferon-β production through promoting mitochondrial antiviral signaling pathway. Our study indicated that indirubin could be a candidate for the therapy of influenza.
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