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erucic acid from Isatis indigotica Fort. suppresses influenza A virus replication and inflammation in vitro and in vivo through modulation of NF-kB and p38 MAPK pathway

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Journal of Pharmaceutical Analysis 2020年第2期10卷 130-146页

作者： Xiaoli Liang Yuan Huang Xiping Pan Yanbing Hao Xiaowei Chen Haiming Jiang Jing Li Beixian Zhou Zifeng Yang State Key Laboratory of Respiratory Diseases Guangzhou Institute of Respiratory HealthNational Clinical Centre of Respiratory DiseaseThe First Affiliated HospitalGuangzhou Medical UniversityGuangzhou510120China Hutchison Whampoa Guangzhou Baiyunshan Chinese Medicine Co. LtdGuangzhou510515China Institute of Combination Chinese and Western Medicine Guangzhou Medical UniversityGuangzhou511436China Department of Pharmacy The People's Hospital of GaozhouGaozhou525200GuangdongChina State Key Laboratory of Quality Research in Chinese Medicine Macao Institute for Applied Research in Medicine and HealthMacao University of Science and TechnologyAvenida Wai LongTaipaMacao999078PR China

Isatis indigotica Fort.(Ban-Lan-Gen)is an herbal medicine prescribed for influenza ***,its active components and mode of action remain mostly *** the present study,erucic acid was isolated from Isatis indigotica Fort.,and subsequently its underlying mechanism against influenza A virus(IAV)infection was investigated in vitro and in *** results demonstrated that erucic acid exhibited broad-spectrum antiviral activity against IAV resulting from reduction of viral polymerase transcription *** acid was found to exert inhibitory effects on IAV or viral(v)RNA-induced pro-inflam-matory mediators as well as interferons(IFNs).The molecular mechanism by which erucic acid with antiviral and anti-inflammatory properties was attributed to inactivation of NF-kB and p38 MAPK ***,the NF-kB and p38 MAPK inhibitory effect of erucic acid led to diminishing the transcriptional activity of interferon-stimulated gene factor 3(ISGF-3),and thereby reducing IAV-triggered pro-inflammatory response amplification in IFN-β-sensitized ***,IAV-or vRNA-triggered apoptosis of alveolar epithelial A549 cells was prevented by erucic *** vivo,erucic acid administration consistently displayed decreased lung viral load and viral antigens ***,erucic acid markedly reduced CD8+cytotoxic T lymphocyte(CTL)recruitment,pro-apoptotic signaling,hyperactivity of multiple signaling pathways,and exacerbated immune inflammation in the lung,which resulted in decreased lung injury and mortality in mice with a mouse-adapted A/FM/1/47-MA(H1N1)strain *** findings provided a mechanistic basis for the action of erucic acid against IAV-mediated inflammation and injury,suggesting that erucic acid may have a therapeutic potential in the treatment of influenza.

关键词： Influenza A virus Isatis indigotica Fort. erucic acid Antiviral Anti-inflammatory NF-kB p38 MAPK Lung injury

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