BACKGROUND: Berberine (Ber), used widely as an antibacterial, antifungal, and anti-inflammatory drug, has long been used as a gastrointestinal remedy in Chinese traditional medicine. Recent reports have suggested that Ber suppresses Th17 responses that was mediated by direct actions on T cells and thymic stromal lymphopoietin production in primary mast cells. It has been suggested that Ber may be useful in treating allergic response. The purpose of this study was to assess the effects of Ber treatment on allergic inflammation in an allergic rhinitis mouse model and to examine the underlying mechanism(s). METHODS: BALB/c mice were divided into control, Derf with no treated (Derf), Ber treated, and Ber with anti-C25 monoclonal antibody treated (Ber + anti-CD25) groups. All mice, with the exception of the control group, were sensitized with an intraperitoneal i.p. injection of Dermatophagoides farinae (Derf). Mice in the Ber and Ber + anti-CD25 group were treated intranasally with 10 #181;g/mL. Then, 1 week after sensitization, all mice were challenged intranasally with 20 #181;g Derf for 5 consecutive days. Mice in the anti-CD25 group were treated intraperitoneally with 250 #181;g anti-CD25 monoclonal antibody 1 day before the first intra-nasal challenge with Derf. Allergic symptom scores, eosinophil counts, and serum Derf-specific IgE levels were measured. T-bet, GATA-3, interferon-g (IFN-γ), interleukin (IL)-10, IL-13, and Foxp3 expression was examined by real-time polymerase chain reaction and Western blotting. CD4⁺ CD25⁺ Foxp3⁺ T cells were assessed by flow cytometry. RESULTS: Symptom scores, serum Derf-specific IgE levels, GATA-3 mRNA levels, T-bet mRNA levels, and tissue eosinophil counts were decreased in the Ber versus the Derf group. In the Ber + anti-CD25 group, serum IL-10 levels were decreased versus the control, Derf, and Ber groups. In the Ber + anti-CD25 mAb groups, Foxp3 mRNA levels were decreased versus the control group. In the Ber group, Foxp3 mRNA levels were increased versus the control group. In the Ber group, the percentage of CD4⁺ CD25⁺ Foxp3⁺ T cells was increased versus the Derf group. The percentage of CD4⁺ CD25⁺ Foxp3+ T cells was increased in the Ber versus the Derf groups. CONCLUSIONS: In our study, Ber reduced allergic inflammation significantly. Moreover, our findings suggest that the mechanism of action of Ber may be via CD4⁺ CD25⁺ Foxp3⁺ Treg cells, possibly through not only by increasing their numbers but also altering their function.
BACKGROUND:Berberine (Ber), used widely as an antibacterial, antifungal, and anti-inflammatory drug, has long been used as a gastrointestinal remedy in Chinese traditional medicine. Recent reports have suggested that Ber suppresses Th17 responses that was mediated by direct actions on T cells and thymic stromal lymphopoietin production in primary mast cells. It has been suggested that Ber may be useful in treating allergic response. The purpose of this study was to assess the effects of Ber treatment on allergic inflammation in an allergic rhinitismouse model and to examine the underlying mechanism(s). METHODS: BALB/c mice were divided into control, Derf with no treated (Derf), Ber treated, and Ber with anti-C25 monoclonal antibody treated (Ber + anti-CD25) groups. All mice, with the exception of the control group, were sensitized with an intraperitoneal i.p. injection of Dermatophagoides farinae (Derf). Mice in the Ber and Ber + anti-CD25 group were treated intranasally with 10 #181;g/mL. Then, 1 week after sensitization, all mice were challenged intranasally with 20 #181;g Derf for 5 consecutive days. Mice in the anti-CD25 group were treated intraperitoneally with 250 #181;g anti-CD25 monoclonal antibody 1 day before the first intra-nasal challenge with Derf. Allergic symptom scores, eosinophil counts, and serum Derf-specific IgE levels were measured. T-bet, GATA-3, interferon-g (IFN-γ), interleukin (IL)-10, IL-13, and Foxp3 expression was examined by real-time polymerase chain reaction and Western blotting. CD4⁺ CD25⁺ Foxp3⁺ T cells were assessed by flow cytometry. RESULTS: Symptom scores, serum Derf-specific IgE levels, GATA-3 mRNA levels, T-bet mRNA levels, and tissue eosinophil counts were decreased in the Ber versus the Derf group. In the Ber + anti-CD25 group, serum IL-10 levels were decreased versus the control, Derf, and Ber groups. In the Ber + anti-CD25 mAb groups, Foxp3 mRNA levels were decreased versus the control group. In the Ber group, Foxp3 mRNA levels were increased versus the control group. In the Ber group, the percentage of CD4⁺ CD25⁺ Foxp3⁺ T cells was increased versus the Derf group. The percentage of CD4⁺ CD25⁺ Foxp3+ T cells was increased in the Ber versus the Derf groups. CONCLUSIONS: In our study, Ber reduced allergic inflammation significantly. Moreover, our findings suggest that the mechanism of action of Ber may be via CD4⁺ CD25⁺ Foxp3⁺ Treg cells, possibly through not only by increasing their numbers but also altering their function.
Authors: Jason R Burchett; Jordan M Dailey; Sydney A Kee; Destiny T Pryor; Aditya Kotha; Roma A Kankaria; David B Straus; John J Ryan Journal: Cells Date: 2022-09-27 Impact factor: 7.666