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      Effect of feeding Chinese herb medicine ageratum-liquid on intestinal bacterial translocations induced by H9N2 AIV in mice

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          As a low pathogenic influenza virus, avian influenza virus subtype H9N2 (H9N2 AIV) often induces high morbidity in association with secondary bacterial infections in chickens or mammals. To explore this phenomenon, the relationship between intestinal microflora changes and bacterial translocations was studied post H9N2 AIV challenge and post AIV infection plus Ageratum-liquid treatment.


          Illumina sequencing, histological examination and Neongreen-tagged bacteria were used in this study to research the microbiota composition, intestinal barrier, and bacterial translocation in six weeks of BALB/c mice.


          H9N2 AIV infection caused intestinal dysbacteriosis and mucosal barrier damages. Notably, the villus length was significantly reduced ( p < 0.01) at 12 dpi and the crypt depth was significantly increased ( p < 0.01) at 5 dpi and 12 dpi with infection, resulting in the mucosal regular villus-length/crypt-depth (V/C) was significantly reduced ( p < 0.01) at 5 dpi and 12 dpi. Moreover, degeneration and dissolution of the mucosal epithelial cells, loose of the connective tissue and partial glandular atrophy were found in infection group, indicating that intestinal barrier function was weakened. Eventually, intestinal microbiota ( Staphylococcus, E. coli, etc.) overrun the intestinal barrier and migrated to liver and lung tissues of the mice at 5 and 12 dpi. Furthermore, the bacteria transferred in mesentery tissue sites from intestine at 36 h through tracking the Neongreen-tagged bacteria. Then the Neongreen-tagged bacteria were isolated from liver at 48 h post intragastrical administration. Simultaneously, Ageratum-liquid could inhibit the intestinal microbiota disorder post H9N2 AIV challenge via the respiratory tract. In addition, this study also illustrated that Ageratum-liquid could effectively prevent intestinal bacterial translocation post H9N2 AIV infection in mice.


          In this study, we report the discovery that H9N2 AIV infection could damage the ileal mucosal barrier and induce the disturbance of the intestinal flora in BALB/c mice resulting in translocation of intestinal bacteria. In addition, this study indicated that Ageratum-liquid can effectively prevent bacterial translocation following H9N2 infection. These findings are of important theoretical and practical significance in prevention and control of H9N2 AIV infection.

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          The online version of this article (10.1186/s12985-019-1131-y) contains supplementary material, which is available to authorized users.

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          Most cited references 26

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          Honokiol, a multifunctional antiangiogenic and antitumor agent.

          Honokiol is a small-molecule polyphenol isolated from the genus Magnolia. It is accompanied by other related polyphenols, including magnolol, with which it shares certain biologic properties. Recently, honokiol has been found to have antiangiogenic, antiinflammatory, and antitumor properties in preclinical models, without appreciable toxicity. These findings have increased interest in bringing honokiol to the clinic as a novel chemotherapeutic agent. In addition, mechanistic studies have tried to find the mechanism(s) of action of honokiol, for two major reasons. First, knowledge of the mechanisms of action may assist development of novel synthetic analogues. Second, mechanistic actions of honokiol may lead to rational combinations with conventional chemotherapy or radiation for enhanced response to systemic cancers. In this review, we describe the findings that honokiol has two major mechanisms of action. First, it blocks signaling in tumors with defective p53 function and activated ras by directly blocking the activation of phospholipase D by activated ras. Second, honokiol induces cyclophilin D, thus potentiating the mitochondrial permeability transition pore, and causing death in cells with wild-type p53. Knowledge of the dual activities of honokiol can assist with the development of honokiol derivatives and the design of clinical trials that will maximize the potential benefit of honokiol in the patient setting.
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            Pathogenesis of emerging avian influenza viruses in mammals and the host innate immune response.

            Influenza A viruses of avian origin represent an emerging threat to human health as the progenitors of the next influenza pandemic. In recent years, highly pathogenic avian influenza H5N1 viruses have caused unprecedented epizootics on three continents and rare but highly fatal disease among humans exposed to diseased birds. Avian viruses of the H7 and H9 subtypes have also infected humans but generally resulted in far milder disease, yet they too should be considered as possible pandemic threats. Influenza virus infection elicits a complex network of host immune responses that, in uncomplicated influenza, results in effective control of the virus and the development of long-term memory responses. However, fatal avian H5N1 virus infection in both humans and experimental mammalian models is characterized by a high viral load in the respiratory tract, peripheral leukopenia and lymphopenia, a massive infiltration of macrophages into the lung, and dysregulation of cytokine and chemokine responses. This review focuses on avian influenza viruses as a pandemic threat, their induction of host innate immune responses in mammalian species, and the contribution of these responses to the disease process.
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              Honokiol is a potent scavenger of superoxide and peroxyl radicals.

              Honokiol, a compound extracted from Magnolia officinalis, has antitumor and antiangiogenic properties in several tumor models in vivo. Among the downstream pathways inhibited by honokiol is nuclear factor kappa beta (NFkappabeta). A prime physiologic stimulus of NFkappabeta is reactive oxygen species. The chemical structure of honokiol suggests that it may be an effective scavenger of reactive oxygen species. In this work, we have studied the reactions of honokiol with superoxide and peroxyl radicals in cell-free and cellular systems using electron spin resonance (ESR) and high-performance liquid chromatography (HPLC) techniques. Honokiol efficiently scavenged superoxide radicals in xanthine oxidase and cytochrome P-450 cell-free systems with the rate constant 3.2x10(5)M(-1)s(-1), which is similar to reactivity of ascorbic acid but 20-times higher than reactivity of vitamin E analog trolox. Honokiol potently scavenged intracellular superoxide within melanoma cells. In addition, honokiol scavenged peroxyl radicals generated by 2,2'-azo-bis(2-amidinopropane hydrochloride) (AAPH). The rate constant of the reaction of honokiol with peroxyl radicals (1.4x10(6)M(-1)s(-1)) was calculated from the competition with spin trap 5-(ethoxycarbonyl)-5-methyl-1-pyrroline N-oxide (EMPO), and was found close to reactivity of trolox (2.5x10(6)M(-1)s(-1)). Therefore, honokiol is an effective scavenger of both superoxide and peroxyl radicals, which may be important for physiological activity of honokiol.

                Author and article information

                Virol J
                Virol. J
                Virology Journal
                BioMed Central (London )
                21 February 2019
                21 February 2019
                : 16
                [1 ]Guangdong experimental high school, Guangzhou, 510145 Gaungdong China
                [2 ]ISNI 0000 0000 9546 5767, GRID grid.20561.30, College of Animal Science, , South China Agricultural University and Guangdong Provincial Key Laboratory of Agro-Animal Genomics and Molecular Breeding and Key Laboratory of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture, ; Guangzhou, 510642 People’s Republic of China
                [3 ]Key Laboratory of Animal Health Aquaculture and Environmental Control, Guangdong Guangzhou, 510642 People’s Republic of China
                [4 ]ISNI 0000 0004 0404 0958, GRID grid.463419.d, USDA, Agriculture Research Service, Avian Disease and Oncology Laboratory, ; East Lansing, MI 48823 USA
                © The Author(s). 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                Funded by: the National Modern Agricultural Industry Technology System Project of China
                Award ID: CARS-41
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100011523, Guangdong Key Laboratory of Innovation Method and Decision Management System;
                Award ID: 2018LM1112
                Award Recipient :
                Funded by: the National Key R&D Program of China
                Award ID: 2017YFD0502001
                Award Recipient :
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                © The Author(s) 2019


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