bufotalin and Disease-Models--Animal

Allergic rhinitis (AR) is one of the most common inflammatory diseases. IgE, inflammatory cytokine production and Th17/Tregs imbalance have been implicated in AR pathogenesis. Bufotalin, a component extracted from toad venom skin secretions and auricular glands, has anti-inflammatory activity and regulates Th17/Tregs balance. Here, the effects of bufotalin on AR were explored.. The AR mice model was established using ovalbumin (OVA). AR mice were treated with bufotalin started on Day 22 with various doses (1, 10, 100 μg or 1 mg per mouse) every day to Day 30. The sneezing and rubbing frequencies were counted. Serum levels of IL-1β, IL-10 and OVA-specific IgE were measured. The superficial cervical lymph nodes were harvested and the percentage of Tregs in lymph node was determined using CD4 and Foxp3 markers.. OVA treatment successfully induced AR model in mice with significantly increased sneezing and rubbing frequency, elevated levels of serum histamine, IL-1β, IL-10 and OVA-specific IgE. Bufotalin treatment significantly ameliorated AR symptoms, with reduced histamine, IgE and IL-1β levels, as well as sneezing and rubbing frequency. Moreover, bufotalin treatment decreased the serum levels of IL-1β, IL-10 and OVA-specific IgE in AR mice.. Bufotalin ameliorated allergic rhinitis symptoms in AR mice by restoring Tregs in lymph node.

Topics: Animals; Cytokines; Disease Models, Animal; Histamine; Immunoglobulin E; Interleukin-10; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic; Sneezing

When Zika virus emerged as a public health emergency there were no drugs or vaccines approved for its prevention or treatment. We used a high-throughput screen for Zika virus protease inhibitors to identify several inhibitors of Zika virus infection. We expressed the NS2B-NS3 Zika virus protease and conducted a biochemical screen for small-molecule inhibitors. A quantitative structure-activity relationship model was employed to virtually screen ∼138,000 compounds, which increased the identification of active compounds, while decreasing screening time and resources. Candidate inhibitors were validated in several viral infection assays. Small molecules with favorable clinical profiles, especially the five-lipoxygenase-activating protein inhibitor, MK-591, inhibited the Zika virus protease and infection in neural stem cells. Members of the tetracycline family of antibiotics were more potent inhibitors of Zika virus infection than the protease, suggesting they may have multiple mechanisms of action. The most potent tetracycline, methacycline, reduced the amount of Zika virus present in the brain and the severity of Zika virus-induced motor deficits in an immunocompetent mouse model. As Food and Drug Administration-approved drugs, the tetracyclines could be quickly translated to the clinic. The compounds identified through our screening paradigm have the potential to be used as prophylactics for patients traveling to endemic regions or for the treatment of the neurological complications of Zika virus infection.

Topics: Animals; Antiviral Agents; Artificial Intelligence; Chlorocebus aethiops; Disease Models, Animal; Drug Evaluation, Preclinical; High-Throughput Screening Assays; Immunocompetence; Inhibitory Concentration 50; Methacycline; Mice, Inbred C57BL; Protease Inhibitors; Quantitative Structure-Activity Relationship; Small Molecule Libraries; Vero Cells; Zika Virus; Zika Virus Infection

Chronic inflammatory autoimmune disease Sjögren's syndrome (SS) is characterized by the reduced secretion of exocrine glands, suggesting strategies targeting inflammation to be a potential option for SS therapy. Bufotalin, an active constituent of Bufadienolides, exerts potent antitumor effects with unknown effects on autoimmune diseases including SS. This study aims to investigate whether bufotalin possesses therapeutic potentials to SS and the underlying mechanisms. The experimental Sjögren's syndrome (ESS) murine model was constructed by SG-immunization and murine naïve CD4

Topics: Animals; Autoantigens; Bufanolides; Disease Models, Animal; Female; Inflammation Mediators; Mice; Mice, Inbred C57BL; Salivary Glands; Sjogren's Syndrome; Th17 Cells