Flavonoids are a class of ingredients with good antiviral activities, and widely found in varieties of traditional Chinese medicine and natural medicine.We made a summary for the antiviral activity of flavonoids in traditional Chinese medicine and natural medicine in the recent years, in the expectation of providing scientific basis for the development and utilization of flavonoid antiviral drugs, as well as their medicinal plant resources.
Key words:
Traditional Chinese medicine
;
Natural medicine
;
Flavonoids
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Antiviral activities
WUW,LIR,LIX,et al.Quercetin as an antiviral agent inhibits influenza A virus (IAV) entry[J].,2016,8(1):6.
Influenza A viruses (IAVs) cause seasonal pandemics and epidemics with high morbidity and mortality, which calls for effective anti-IAV agents. The glycoprotein hemagglutinin of influenza virus plays a crucial role in the initial stage of virus infection, making it a potential target for anti-influenza therapeutics development. Here we found that quercetin inhibited influenza infection with a wide spectrum of strains, including A/Puerto Rico/8/34 (H1N1), A/FM-1/47/1 (H1N1), and A/Aichi/2/68 (H3N2) with half maximal inhibitory concentration (IC50) of 7.756 ± 1.097, 6.225 ± 0.467, and 2.738 ± 1.931 μg/mL, respectively. Mechanism studies identified that quercetin showed interaction with the HA2 subunit. Moreover, quercetin could inhibit the entry of the H5N1 virus using the pseudovirus-based drug screening system. This study indicates that quercetin showing inhibitory activity in the early stage of influenza infection provides a future therapeutic option to develop effective, safe and affordable natural products for the treatment and prophylaxis of IAV infections.
VAIDYAB,CHOS,OHK,et al.Effectiveness of periodic treatment of quercetin against influenza A virus H1N1 through modulation of protein expression[J].,2016,64(21):4416-4425.
Kimchi, a traditional fermented food regularly consumed in Korea, contains various types of antimicrobial compounds. Among the tested compounds present in common spices used in Kimchi, quercetin showed the highest selectivity index against influenza A virus (IAV) H1N1. In this study, the effect of pretreatment and periodic treatment with quercetin against IAV in Madinarby canine kidney cells was observed. Compared to pretreatment, periodic treatment resulted in significantly higher cell viability but lower relative expression of the IAV PA gene and total apoptosis and cell death. To explain the mechanisms underlying the antiviral effects of quercetin treatment, a comparative proteomic analysis was performed in four samples (mock, quercetin-treated, IAV-infected, and quercetin-treated IAV-infected). Among the 220 proteins, 56 proteins were classified nonhierarchically into three clusters and were differentially modulated by quercetin treatment in IAV-infected cells. Post-translational modifications were ...
CHOI EJ,KIM HB,BAEK YH,et al.Differential microRNA expression following infection with a mouse-adapted,highly virulent avian H5N2 virus[J].,2014,14(1):252.
Background MicroRNAs (miRNAs) are known to regulate various biological processes, including expression of cellular gene and virus-induced inflammation. Recently, studies have indicated that some miRNAs could regulate influenza virus replication. Due to differential sensitivities of influenza A virus strains to different species (avian and mammalian), variations in host responses may be observed. Therefore, we investigated and compared the differences in global host miRNA expression in mouse lungs infected with wild type low pathogenicity A/Aquatic bird/Korea/w81/2005 (H5N2) (w81) or mouse-adapted virulent A/Aquatic bird /Korea/ma81/2007 (H5N2) (ma81) virus. Results Although the mice infected with ma81 exhibited much greater mortality than w81-infected mice, the parental w81 virus induced a higher number of differentially expressed miRNAs compared to the ma81 virus. Between these 2 viruses, a total of 27 and 20 miRNAs were commonly expressed at 1 dpi and 3 dpi, respectively. It is noteworthy that only 9 miRNAs (miR-100-5p, miR-130a-5p, miR-146b-3p, miR-147-3p, miR-151-5p, miR-155-3p, miR-223-3p, miR-301a-3p, and miR-495-3p) were significantly upregulated in both lungs infected with either wild type w81 or the mouse-adapted ma81 strain at both time points. Notably, expression levels of miR-147-3p, miR-151-5p, miR-155-3p, and miR-223-3p were higher in the lungs of mice infected with the ma81 virus than those infected with the w81 virus. To identify potential roles of these miRNAs in regulating influenza virus replication, each group of mice was intranasally treated with each inhibitor of specifically targeting 4 miRNAs, and then challenged with 5 mouse lethal dose 50% (MLD 50 ) of the virulent ma81 virus on the following day. Although the specific miRNA inhibitors could not completely attenuate mortality or reduce viral replication, the miR-151-5p- and miR-223-3p-inhibitors reduced mortality of inoculated mice to 70% and substantially delayed death. Conclusions Our results suggest that the mammalian adaptation of avian influenza A virus results in a different miRNA expression pattern in lungs of virus-infected mice compared with its parental strain, and use of specific miRNA inhibitors to target genes associated with the immune response or cell death may affect virulence and virus replication.
LING JX,WEIF,LIN,et al.Amelioration of influenza virus-induced reactive oxygen species formation by epigallocatechin gallate derived from green tea[J].,2012,33(12):1533-1541.
AIM: To study whether epigallocatechin gallate (EGCG), a green tea-derived polyphenol, exerted anti-influenza A virus activity in vitro and in vivo. METHODS: Madin-Darby canine kidney (MDCK) cells were tested. The antiviral activity of EGCG in the cells was determined using hemagglutination assay and qPCR. Time of addition assay was performed to determine the kinetics of inhibition of influenza A by EGCG. The level of reactive oxygen species (ROS) were determined with confocal microscopy and flow cytometry. BALB/c mice were treated with EGCG (10, 20 or 40 mg·kg(-1)·d(-1), po) for 5 d. On the 3rd d of the treatment, the mice were infected with influenza A virus. Histopathological changes, lung index and virus titers in the lungs were determined. RESULTS: Treatment of influenza A-infected MDCK cells with EGCG (1.25-100 nmol/L) inhibited influenza A replication in a concentration-dependent manner (the ED(50) value was 8.71±1.11 nmol/L). Treatment with EGCG (20 nmol/L) significantly suppressed the increased ROS level in MDCK cells following influenza A infection. In BALB/c mice infected with influenza virus, oral administration of EGCG (40 mg·kg(-1)·d(-1)) dramatically improved the survival rate, decreased the mean virus yields and mitigated viral pneumonia in the lungs, which was equivalent to oral administration of oseltamivir (40 mg·kg(-1)·d(-1)), a positive control drug. CONCLUSION: The results provide a molecular basis for development of EGCG as a novel and safe chemopreventive agent for influenza A infection.
VLAHOSR,STAMBASJ,SELEMIDISS.Suppressing production of reactive oxygen species (ROS) for influenza A virus therapy[J].,2012,33(1):3-8.
Influenza A viral infections claim millions of lives worldwide and continue to impose a major burden on healthcare systems. Current pharmacological strategies to control influenza A virus-induced lung disease are problematic owing to antiviral resistance and the requirement for strain-specific vaccination. The production of reactive oxygen species (ROS), particularly superoxide, is an important host defence mechanism for killing invading pathogens. However, excessive superoxide may be detrimental following influenza A virus infection. Indeed, suppression of superoxide production by targeting the primary enzymatic source of superoxide in mammalian inflammatory cells, NADPH oxidase 2 (Nox2), markedly alleviates influenza A virus-induced lung injury and virus replication, irrespective of the infecting strain. Therefore, we propose that Nox2 oxidase inhibitors, in combination with current therapeutics (i.e. antivirals and vaccines), could be useful for suppression of influenza A virus-induced lung disease.
目的:探讨桑白皮不同有效部位群对小鼠呼吸道合胞病毒肺炎病毒载量的影响。方法小鼠按体质量等级随机分为5组,分别为正常组、模型组、桑白皮总黄酮组、桑白皮总多糖组、病毒唑组,每组30只。以呼吸道合胞病毒滴鼻感染小鼠,治疗组分别予桑白皮总黄酮、桑白皮总多糖、病毒唑干预。每日观察小鼠的生存状态;呼吸道合胞病毒感染后3、5、7 d 计算肺指数,实时荧光定量PCR(real time RT - PCR)检测小鼠肺组织中病毒载量。结果模型组与正常组比较肺指数在不同时间点有不同程度的增高( P ﹤0.05);各治疗组与模型组比较,第3、5、7天肺指数均明显降低( P ﹤0.05),总黄酮及总多糖组明显优于病毒唑组( P ﹤0.05)。正常组肺组织未检测到呼吸道合胞病毒,模型组病毒载量随时间逐渐增多。各治疗组与模型组相比各时间点病毒载量有不同程度降低,但桑白皮总黄酮组最低,与桑白皮总多糖及病毒唑组比较差异有统计学意义( P ﹤0.05)。结论桑白皮总黄酮对呼吸道合胞病毒肺炎有一定的治疗作用,优于桑白皮总多糖及病毒唑组。
SUEDEEA,TEWTRAKULS,PANICHAYUPAKARANA-NTP.Anti-HIV-1 integrase compound from Pometia pinnata leaves[J].,2013,51(10):1256-1261.
HIV-1 integrase (HIV-1 IN) is a key enzyme involved in the replication cycle of the retrovirus. Any new knowledge on inhibitors of this enzyme could provide essential clues for the development of anti-HIV drugs.To evaluate anti-HIV-1 IN activity of some Thai medicinal plant extracts, and the extract that possessed the strongest anti-HIV-1 IN activity was subjected to isolation of the active compounds.Ethanol extracts of eight Thai medicinal plants were evaluated for their inhibitory effect against HIV-1 IN. An extract of Pometia pinnata J. R. Forst. & G. Forst (Sapindaceae) leaves that possessed the strongest anti-HIV-1 IN activity was fractionated to isolate the active compounds by anti-HIV-1 IN assay-guided isolation process.The leaf extract from P. pinnata had the strongest anti-HIV-1 IN activity with an IC50 value of 8.8 08g/mL. An anti-HIV-1 IN assay-guided isolation of the active compounds from a leaf extract of P. pinnata resulted in the isolation of one active compound, identified as proanthocyanidin A2. Proanthocyanidin A2 showed satisfactory anti-HIV-1 IN activity with an IC50 value of 30.1 08M. Three flavonoids, epicatechin, kaempferol-3-O-rhamnoside, quercetin-3-O-rhamnoside; a glycolipid, 1-O-palmitoyl-3-O-[α-.-galactopyranosyl-(165→65 6)-β-.-galactopyranosyl]-sn-glycerol; a steroidal glycoside; stigmasterol-3-O-glucoside; and a pentacyclic triterpenoid saponin, 3-O-α-.-arabinofuranosyl-(165→653)-[α-.-rhamnopyranosyl-(165→65 2)]-α-.-arabinopyranosyl hederagenin were also isolated but were inactive at a concentration of 1006508M.
COTINS,CALLISTEC,MAZERONM,et al.Eight flavonoids and their potential as inhibitors of human cytomegalovirus replication[J].,2012,96(2):181-186.
The drugs currently available for treatment of severe human cytomegalovirus (HCMV) infections suffer from many drawbacks, particularly toxicity, and potential teratogenicity contraindicating their use in target populations such as pregnant women. The emergence of drug-resistant strains is still a problem for disease management, particularly in immunosuppressed populations where antivirals are used for extended periods of time. The flavonoid family of drugs contains promising candidates as they have low toxicity and inhibit different targets to currently available antivirals. We report here that, unlike their chalcon homologs, four flavonoids (baicalein, quercetin, quercetagetin and naringenin) inhibit various stages of HCMV replication, the most active anti-HCMV compound being baicalein and the less active and less selective being quercetagetin. These drugs could provide potential inhibitors of virus replication alone or in combination, without increased toxicity.
O'CONNOR CM,VANICEK J,MURPHY E A.Host microRNA regulation of human cytomegalovirus immediate early protein translation promotes viral latency[J].,2014,88(10):5524-5532.
Abstract Reactivation of human cytomegalovirus (HCMV) is a significant cause of disease and death in immunocompromised patients, underscoring the need to understand how latency is controlled. Here we demonstrate that HCMV has evolved to utilize cellular microRNAs (miRNAs) in cells that promote latency to regulate expression of a viral protein critical for viral reactivation. Our data reveal that hsa-miR-200 miRNA family members target the UL122 (immediate early protein 2) 3' untranslated region, resulting in repression of this viral protein. Utilizing recombinant viruses that mutate the miRNA-binding site compared to the sequence of the wild-type virus results in lytic rather than latent infections in ex vivo infections of primary CD34+ cells. Cells permissive for lytic replication demonstrate low levels of these miRNAs. We propose that cellular miRNA regulation of HCMV is critical for maintenance of viral latency. IMPORTANCE: Human cytomegalovirus (HCMV) is a herpesvirus that infects a majority of the population. Once acquired, individuals harbor the virus for life, where the virus remains, for the most part, in a quiet or latent state. Under weakened immune conditions, the virus can reactivate, which can cause severe disease and often death. We have found that members of a family of small RNAs, termed microRNAs, encoded by human myeloid progenitor cells are capable of repressing a key viral protein, thus enabling the virus to ensure a quiet/latent state. As these progenitor cells mature further down the myeloid lineage toward cells that support active viral replication, the levels of these microRNAs decrease. Together, our data suggest that host cell microRNA regulation of HCMV is important for the quiet/latent state of this pathogen.
STEED AL,CHRISTOPHI GP,KAIKO GE,et al.The microbial metabolite desaminotyrosine protects from influenza through type I interferon[J].,2017,357(6350):498-502.
The microbiota is known to modulate the host response to influenza infection through as-yet-unclear mechanisms. We hypothesized that components of the microbiota exert effects through type I interferon (IFN), a hypothesis supported by analysis of influenza in a gain-of-function genetic mouse model. Here we show that a microbially associated metabolite, desaminotyrosine (DAT), protects from influenza through augmentation of type I IFN signaling and diminution of lung immunopathology. A specific human-associated gut microbe, Clostridium orbiscindens, produced DAT and rescued antibiotic-treated influenza-infected mice. DAT protected the host by priming the amplification loop of type I IFN signaling. These findings show that specific components of the enteric microbiota have distal effects on responses to lethal infections through modulation of type I IFN.