In vivo antibacterial activity of medicinal plant Sophora flavescens against Streptococcus agalactiae infection.

Streptococcosis disease caused by Streptococcus agalactiae (Group B Streptococcus, GBS) results in a huge economic loss of tilapia culture. It is urgent to find new antimicrobial agents against streptococcosis. In this study, 20 medicinal plants were evaluated in vitro and in vivo to obtain medicinal plants and potential bioactive compounds against GBS infection. The results showed that the ethanol extracts of 20 medicinal plants had low or no antibacterial properties in vitro, with a minimal inhibitory concentration ≥256 mg/L. Interestingly, in vivo tests showed that 7 medicinal plants could significantly inhibit GBS infection in tilapia, and Sophora flavescens (SF) had the strongest anti-GBS activity in tilapia, reaching 92.68%. SF could significantly reduce the bacterial loads of GBS in different tissues (liver, spleen and brain) of tilapia after treated with different tested concentrations (12.5, 25.0, 50.0 and 100.0 mg/kg) for 24 h. Moreover, 50 mg/kg SF could significantly improve the survival rate of GBS-infected tilapia by inhibiting GBS replication. Furthermore, the expression of antioxidant gene cat, immune-related gene c-type lysozyme and anti-inflammatory cytokine il-10 in liver tissue of GBS-infected tilapia significantly increased after treated with SF for 24 h. Meanwhile, SF significantly reduced the expression of immune-related gene myd88 and pro-inflammatory cytokines il-8 and il-1ß in liver tissue of GBS-infected tilapia. The negative and positive models of UPLC-QE-MS, respectively, identified 27 and 57 components of SF. The major components of SF extract in the negative model were α, α-trehalose, DL-malic acid, D- (-)-fructose and xanthohumol, while in the positive model were oxymatrine, formononetin, (-)-maackiain and xanthohumol. Interestingly, oxymatrine and xanthohumol could significantly inhibit GBS infection in tilapia. Taken together, these results suggest that SF can inhibit GBS infection in tilapia, and it has potential for the development of anti-GBS agents.

Natural component geniposide enhances survival rate of crayfish Procambarus clarkii infected with white spot syndrome virus.

White Spot Disease (WSD), caused by white spot syndrome virus (WSSV), is an acute and highly lethal viral disease of shrimp. Currently, there are no commercially available drugs to control WSD. It is urgent and necessary to find anti-WSSV drugs. Natural compounds are an important source of antiviral drug discovery. In this study, the anti-WSSV activity of natural compound geniposide (GP) was investigated in crayfish Procambarus clarkii. Results showed that GP had a concentration-dependent inhibitory effect on WSSV replication in crayfish at 24 h, and highest inhibition was more than 98%. In addition, GP significantly inhibited the expression of WSSV immediate-early gene ie1, early gene DNApol, late gene VP28. The mortality of WSSV-infected crayfish in control groups was 100%, while it reduced by 70.0% when treated with 50 mg/kg GP. Co-incubation, pre-treatment and post-treatment experiments showed that GP could prevent and treat WSSV infection in crayfish by significantly inhibiting WSSV multiplication. Mechanistically, the syntheses of WSSV structural proteins VP19, VP24, VP26 and VP28 were significantly inhibited by GP in S2 cells. Furthermore, GP could also suppress WSSV replication by blocking the expression of antiviral immunity-related factor STAT to reduce ie1 transcription. Moreover, GP possessed anti-inflammatory and anti-oxidative activity in crayfish. Overall, GP has the potential to be developed as a preventive or therapeutic agent against WSSV infection.

Natural component plumbagin as a potential antibacterial agent against Streptococcus agalactiae infection.

Streptococcus agalactiae, also known as Group B Streptococcus (GBS), can infect humans, terrestrial animals and fish. The emergence of bacterial resistance of S. agalactiae to antibiotics leads to an urgent need of exploration of new antimicrobial agents. In the study, the antibacterial activity of natural component plumbagin (PLB) against S. agalactiae was investigated in vitro and in vivo. The results showed that the minimal inhibitory concentration (MIC) of PLB against S. agalactiae was 8 mg/L. The growth curve assay revealed that PLB could inhibit the growth of S. agalactiae. In addition, the time-killing curve showed that S. agalactiae was killed almost completely by 2-fold MIC of PLB within 12 h. Transmission electron microscopy results showed obvious severe morphological destruction and abnormal cells of S. agalactiae after treated with PLB. The pathogenicity of S. agalactiae to zebrafish was significantly decreased after preincubation with PLB for 2 h in vitro, further indicating the bactericidal activity of PLB. Interestingly, PLB could kill S. agalactiae without inducing resistance development. Furthermore, pretreatment and post-treatment assays suggested that PLB also exhibited the antibacterial activity against S. agalactiae infection in vivo by effectively reducing the bacterial load and improving the survival rate of S. agalactiae-infected zebrafish. In summary, PLB had potent antibacterial activity against S. agalactiae in vitro and in vivo, and it could be an excellent antimicrobial candidate to prevent and control S. agalactiae infection.

The Long Noncoding RNA 150Rik Promotes Mesangial Cell Proliferation via miR-451/IGF1R/p38 MAPK Signaling in Diabetic Nephropathy.

BACKGROUND/AIMS: Diabetic nephropathy (DN) as the primary cause of end-stage kidney disease is a common complication of diabetes. However, the initiating molecular events triggering DN are unknown. Recently, long noncoding RNAs (lncRNAs) have been shown to play important roles in DN. METHODS: The expression level of lncRNA 1500026H17Rik (150Rik for short) was measured by qRT-PCR (quantitative real-time PCR). Cell proliferation ability was detected by 5-Ethynyl-2'-deoxyuridine (EdU). The relationship between 150Rik and microRNA 451 (miR-451) was examined by luciferase assay and RNA immunoprecipitation (RIP) assay. Finally, the effect of 150Rik on cell proliferation through the miR-451/insulin-like growth factor 1 receptor (IGF1R)/mitogen-activated protein kinases (p38MAPK) pathway was detected by EdU, flow cytometry analysis, western blot. RESULTS: We found that 150Rik, an evolutionarily conserved lncRNA, was significantly upregulated in renal tissue of db/db DN mice and in mesangial cells (MCs) cultured under a high glucose condition. Further, overexpression or knockdown of 150Rik was found to regulate cell proliferation in MCs. Moreover, 150Rik was found to interact with miR-451 in both a direct and argonaute-2 (Ago2)-dependent manner. Results also revealed that overexpression of 150Rik inhibited cell proliferation through the miR-451/IGF1R/p38MAPK pathway in MCs under the high glucose condition, while knockdown of 150Rik increased cell proliferation via the miR-451/IGF1R/p38MAPK pathway. CONCLUSION: Taken together, these results provide new insight into the association between 150Rik and the miR-451/IGF1R/p38MAPK signaling pathway during DN progression.