PMID- 29091888 OWN - NLM STAT- MEDLINE DCOM- 20180803 LR - 20180803 IS - 1950-6007 (Electronic) IS - 0753-3322 (Linking) VI - 97 DP - 2018 Jan TI - Oroxylin A suppresses influenza A virus replication correlating with neuraminidase inhibition and induction of IFNs. PG - 385-394 LID - S0753-3322(17)34046-5 [pii] LID - 10.1016/j.biopha.2017.10.140 [doi] AB - Because it is highly contagious, the influenza A virus (IAV) has the potential to cause pandemics in humans. The emergence of drug-resistant strains requires the development of new chemical therapeutics. Oroxylin A (OA) is a flavonoid which has been shown to have antioxidant and antitumor effects. However, intensive studies in which OA fights against different influenza virus strains and the underlying antiviral mechanisms have not been reported. In our study, the antiviral activities in cells and in mice, the preliminary mechanisms of OA were investigated. Our data show that it can inhibit A/FM/1/47 (H1N1), A/Beijing/32/92 (H3N2) and oseltamivir-resistant A/FM/1/47-H275Y (H1N1-H275Y) viruses in MDCK cells in a dose-dependent manner with inhibitory rates of 70.9%, 59.5% and 23.2%, respectively, at 50muM doses. Orally administered OA effectively protected mice from H1N1 virus-induced death, body weight loss and lung injury, with a survival rate of 60.0% at 100mg/kg/d dose. In addition, the H1N1 M1 gene transcription and protein synthesis were suppressed by 43.7% and 33.2%, respectively, in the late biosynthesis stage. This resulted in inhibition of viral replication. Furthermore, we found that OA has a neuraminidase (NA) inhibitory effect with IC(50) values for H1N1-H275Y and A/Anhui/1/2013-R294K (H7N9-R294K) of 241.4muM and 203.6muM, respectively. Interferons (IFNs) produced by the virally infected cells play important roles in antiviral defense, therefore, IFN levels in the blood were also tested in mice. We found that IFN-beta and IFN-gamma in the OA 100mg/kg/d group were markedly increased by 24.5pg/mL and 859.9pg/mL, respectively, compared with those in the model group. This indicated that OA could induce the secretion of IFNs. The potent inhibition of virus replication and NA inhibitory activity, as well as the promotion of IFN production suggest that OA could be a drug candidate to fight against IAVs including oseltamivir-resistant strains. CI - Copyright (c) 2017 Elsevier Masson SAS. All rights reserved. FAU - Jin, Jing AU - Jin J AD - State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, Jiangsu, PR China. FAU - Chen, Shuo AU - Chen S AD - State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, Jiangsu, PR China. FAU - Wang, Dechuan AU - Wang D AD - Department of Organic Chemistry, School of Science, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, Jiangsu, PR China. FAU - Chen, Yuanjin AU - Chen Y AD - State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, Jiangsu, PR China. FAU - Wang, Yuxu AU - Wang Y AD - State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, Jiangsu, PR China. FAU - Guo, Min AU - Guo M AD - State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, Jiangsu, PR China. FAU - Zhou, Changlin AU - Zhou C AD - State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, Jiangsu, PR China. Electronic address: cl_zhou@cpu.edu.cn. FAU - Dou, Jie AU - Dou J AD - State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, Jiangsu, PR China. Electronic address: doujie@cpu.edu.cn. LA - eng PT - Journal Article DEP - 20171106 PL - France TA - Biomed Pharmacother JT - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JID - 8213295 RN - 0 (Antiviral Agents) RN - 0 (Enzyme Inhibitors) RN - 0 (Flavonoids) RN - 53K24Z586G (5,7-dihydroxy-6-methoxy-2-phenylchromen-4-one) RN - 9008-11-1 (Interferons) RN - EC 3.2.1.18 (Neuraminidase) SB - IM MH - Animals MH - Antiviral Agents/*pharmacology MH - CHO Cells MH - Cricetinae MH - Cricetulus MH - Dogs MH - Dose-Response Relationship, Drug MH - Enzyme Inhibitors/pharmacology MH - Flavonoids/*pharmacology MH - Influenza A Virus, H1N1 Subtype/*drug effects/physiology MH - Interferons/*biosynthesis MH - Madin Darby Canine Kidney Cells MH - Mice, Inbred ICR MH - Neuraminidase/*antagonists & inhibitors/metabolism MH - Virus Replication/*drug effects/physiology OTO - NOTNLM OT - Antiviral activity OT - IFNs OT - Influenza A virus OT - Neuraminidase OT - Oroxylin A EDAT- 2017/11/02 06:00 MHDA- 2018/08/04 06:00 CRDT- 2017/11/02 06:00 PHST- 2017/08/10 00:00 [received] PHST- 2017/10/18 00:00 [revised] PHST- 2017/10/24 00:00 [accepted] PHST- 2017/11/02 06:00 [pubmed] PHST- 2018/08/04 06:00 [medline] PHST- 2017/11/02 06:00 [entrez] AID - S0753-3322(17)34046-5 [pii] AID - 10.1016/j.biopha.2017.10.140 [doi] PST - ppublish SO - Biomed Pharmacother. 2018 Jan;97:385-394. doi: 10.1016/j.biopha.2017.10.140. Epub 2017 Nov 6.