lignans and Fish-Diseases

Spring viraemia of carp virus (SVCV) poses a serious threat to aquaculture industry due to the lack of approved antiviral treatments. Therefore, a novel arctigenin derivative, 4-(2-methylimidazole) octanoxy-arctigenin (MON), was synthesized to assess the antiviral activity against SVCV in vitro and in vivo. The results indicated MON decreased the SVCV glycoprotein (G) gene expression in vitro by a maximum inhibitory rate of > 99% at 3.5 μM. Furthermore, MON showed the protective effect on epithelioma papulosum cyprinid (EPC) cells and considerably decreased the cytopathic effect (CPE). More importantly, MON inhibited SVCV G gene expression levels in vitro at the half-maximal activity (IC

Topics: Animals; Antiviral Agents; Carps; Fish Diseases; Furans; Lignans; Rhabdoviridae; Rhabdoviridae Infections; Zebrafish

Topics: Animals; Bass; Biphenyl Compounds; Female; Fish Diseases; Lignans; Rhabdoviridae

Arctigenin derivatives form an elite class of naturally occurring compounds that possess promising antiviral therapeutic perspectives. In a previous study, we design and synthesize a arctigenin derivative, 4-(8-(2-ethylimidazole)octyloxy)-arctigenin (EOA), to evaluate its antiviral activity on infectious hematopoietic necrosis virus (IHNV). In this study, we find that the half maximal inhibitory concentrations (IC

Topics: Animals; Antiviral Agents; Cell Line; Fish Diseases; Furans; Imidazoles; Infectious hematopoietic necrosis virus; Lignans; Rhabdoviridae Infections

Topics: Animals; Antiviral Agents; Aquaculture; Cell Line; Fish Diseases; Fishes; Furans; Lignans; Rhabdoviridae; Rhabdoviridae Infections; Virus Replication

Viral diseases in aquaculture were challenging because there are few preventative measures and/or treatments. Our previous study indicated that imidazole arctigenin derivatives possessed antiviral activities against infectious hematopoietic necrosis virus (IHNV). Based on the structure-activity relationship in that study, a new imidazole arctigenin derivative, 4-(8-(2-ethylimidazole)octyloxy)-arctigenin (EOA), was designed, synthesized and its anti-IHNV activity was evaluated. By comparing inhibitory concentration at half-maximal activity (IC

Topics: Animals; Antiviral Agents; Cell Line, Tumor; Drug Evaluation, Preclinical; Fish Diseases; Furans; Infectious hematopoietic necrosis virus; Lignans; Microbial Sensitivity Tests; Oncorhynchus mykiss; Rhabdoviridae Infections

Many natural products from medicinal plants are small molecular weight compounds with enormous structural diversity and show various biological activities. Magnolol is a biphenol compound rich in the stem bark of Magnolia officinalis Rehd et Wils., and is able to suppress viral replication in GCRV-infected grass carp (Ctenopharyngodon idella) kidney (CIK) cells in the previous study. In this study, in vivo studies demonstrated that magnolol was efficient to restrain the replication of GCRV and repair the low level of superoxide dismutase and total antioxidant capacity in serum at the non-toxic concentration in vivo. Furthermore, magnolol inhibited CIK cell apoptosis induced by GCRV and kept the normal cellular morphological structure, reflecting in the protection of CIK cells from cell swelling, the formation of apoptotic bodies, the disappearance of cellular morphology and nuclear fragmentation. Reverse transcript quantitative polymerase chain reaction (RT-qPCR) showed that magnolol facilitated the expression of apoptosis-inhibiting gene bcl-2, while suppressed the expression of apoptosis-promoting gene bax in GCRV-infected cells. Besides, RT-qPCR and enzyme activity assays proved that magnolol suppressed the expression of caspase 3, caspase 8 and caspase 9. Moreover, interactions between magnolol and proteins were predicted by using the STITCH program, which revealed that ten proteins including caspase 3, were involved in the apoptosis pathway, p53 signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway and toll-like receptor signaling pathway. Further assays were performed to test the effect of magnolol on apoptosis pathway, which showed that magnolol dramatically inhibited the activity of caspase 3 rather than those of caspase 8 and caspase 9. Collectively, the present study revealed that magnolol heightened the resistance of grass carp against GCRV infection and refrained GCRV-induced apoptosis, which may be attributed to the direct interaction of magnolol with caspase 3. The present results make a contribution to understanding the mechanisms by which small-molecule drugs possess antiviral activities, and lay a foundation for the development of broad-spectrum antiviral compounds in aquaculture industry.

Topics: Animals; Antiviral Agents; Apoptosis; Biphenyl Compounds; Carps; Cell Line; Cytopathogenic Effect, Viral; Fish Diseases; Immunity, Innate; Lignans; Reoviridae; Reoviridae Infections

Aeromonas hydrophila is a common zoonotic pathogen which can cause several infections both in human and animals, particular aquatic animals. Antibiotics have been widely used in the treatment of A. hydrophila infections, however, the development of resistance has limited the treatment for these infections. There is an urgent need for novel agents and strategies against these infections. Aerolysin, a pore-forming toxin secreted by most pathogenic A. hydrophila, is known to contribute to the pathogenesis of A. hydrophila infections. Therefore, aerolysin has been identified as a potential target for drug discovery. In this paper, we found that magnolol, a natural compound without anti -A. hydrophila activity, could significantly inhibit the hemolytic activity of A. hydrophila culture supernatants by inhibiting the transcription of the aerolysin encoding gene aerA at low concentrations. Furthermore, the survival assay showed that magnolol could significantly reduce the mortality induced by A. hydrophila infection in channel catfish (Ictalurus punctatus). Taken together, these findings provide a potent agent against A. hydrophila infections.

Topics: Aeromonas hydrophila; Animals; Bacterial Toxins; Biphenyl Compounds; Fish Diseases; Gram-Negative Bacterial Infections; Hemolysis; Ictaluridae; Lignans; Microbial Sensitivity Tests; Pore Forming Cytotoxic Proteins; Virulence Factors

Medicinal plants have been widely used for a long history. Exploration of pharmacologically active compounds from medicinal plants present a broad prevalent of application. By examining viral mRNA expression in GCRV-infected Ctenopharyngodon idella kidney (CIK) cells treated with thirty kinds of plant extracts, we identified Magnolia officinalis Rehd et Wils. was able to preferably suppress viral replication. Further studies demonstrated that the main ingredients of magnolia bark, namely, magnolol and honokiol presented protective pharmacological function when treated GCRV-infected CIK cells with a concentration of 2.00 μg/ml and 1.25 μg/ml, respectively. Furthermore, reverse transcript quantitative polymerase chain reaction (RT-qPCR) and western blot showed that both magnolol and honokiol were efficient to restrain the replication of GCRV in CIK cells at non-toxic concentration (2.51 ± 0.51 μg/ml for magnolol, and 3.18 ± 0.61 μg/ml for honokiol). Moreover, it was found that magnolol and honokiol promoted the expression of immune-related genes. Magnolol obviously significantly increased the expression of interferon (IFN) regulatory factor (IRF)7 rather than that of IRF3 in the GCRV-infected cells, leading to the activation of type I IFN (IFN-I). Simultaneously, magnolol drastically facilitated the expression of interleukin (IL)-1β, but failed to induce the molecules in nuclear factor (NF)-κB pathways. Differently, honokiol strikingly motivated not only the expression of IL-1β, but also those of tumor necrosis factor α (TNFα) and NF-κB. Interestingly, though honokiol motivated the expression of IFN-β promoter stimulator 1 (IPS-1), IRF3 and IRF7, it failed to up-regulate the expression of IFN-I, indicating that honokiol enhanced the host innate antiviral response to GCRV infection via NF-κB pathways. Collectively, the present study revealed that magnolol and honokiol facilitated the expression of innate immune-related genes to strengthen the innate immune signaling responses to resist GCRV infection, which contributed to understanding the mechanisms by which small-molecule drugs possessed antiviral activities. In addition, these results lay a foundation for the development of broad-spectrum antiviral compounds in aquaculture industry.

Topics: Animals; Biphenyl Compounds; Carps; Cell Line; Colorimetry; Cytopathogenic Effect, Viral; Fish Diseases; Immunity, Innate; Lignans; Magnolia; Reoviridae; Reoviridae Infections; Tetrazolium Salts; Thiazoles

The present study was to investigate the protective effect and possible mechanism of phyllanthin against carbon tetrachloride (CCl4)-induced hepatocyte damage in carp. Phyllanthin (5, 10, and 15 μg/ml) was added to carp primary hepatocytes before (pre-treatment) and after (post-treatment) incubation of the hepatocytes in medium containing CCl4 at 8 mM; supernatant and cell were collected for the analyses of cell viability, biochemical parameters, and gene expression. The results showed that phyllanthin at the concentration of 15 μg/ml significantly suppressed the elevation of glutamate pyruvate transaminase (GPT), glutamate oxalate transaminase (GOT), lactate dehydrogenase (LDH), and malondialdehyde (MDA), and the reduction of cell viability, superoxide dismutase (SOD) activity, cytochrome P450 1a (CYP1A), and cytochrome P450 3a (CYP3A) messenger RNA (mRNA) levels expect LDH in the post-treatment. The levels of GPT, GOT, and CYP1A mRNA were also effectively restored in the pretreatment with phyllanthin (10 μg/ml). Overall, our results suggested that phyllanthin may be used as a hepatoprotective agent to prevent liver diseases in fish.

Topics: Animals; Carbon Tetrachloride; Carps; Cell Survival; Fish Diseases; Hepatocytes; Lignans; Liver; Protective Agents