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Berberine Attenuates Inflammation Associated with Delayed-Type Hypersensitivity via Suppressing Th1 Response and Inhibiting Apoptosis

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ABSTRACT

Berberine, one of the active alkaloids from Rhizoma Coptidis, has been indicated to have anti-inflammatory and immunosuppressive properties. The aim of this study was to determine the role of berberine on ovalbumin (OVA)-induced delayed-type hypersensitivity (DTH) and its potential mechanisms. Berberine treatment significantly reduced footpad swelling, inflammatory cells infiltration, anti-OVA IgG levels, IgE concentration in serum, and the tetramer+CD8+ cells. In homogenized footpad tissue, the production of Th1-mediated cytokines including IFN-γ, TNF-α, and IL-2 were suppressed following the administration of berberine. Detailed studies revealed that berberine prevented differentiation into Th1 cells in the OVA-primed lymphocytes, resulting from suppressing the expression of T-bet and secretion of IFN-γ but not IL-4. Concanavalin A stimulation assay and MTT assay also indicated inhibiting effect of berberine treatment on IFN-γ production and decreased cytotoxicity in lymphocytes proliferation, respectively. Additionally, berberine obviously decreased the cell apoptosis and enzymatic activity of caspase-3, which was further confirmed by the facts that berberine clearly lowered Bax/Bcl-2 ratio and expression of cleaved caspase-3 protein. On correlation analysis, the percentage of apoptotic cells showed a significant positive relationship with IFN-γ/IL-4 ratio of supernatant from footpad tissue in berberine-treated DTH mice. These results demonstrated that berberine attenuated Th1-mediated inflammation in OVA-induced DTH by curbing Th1 response and inhibiting cell apoptosis, suggesting a therapeutic potential for berberine for the treatment of type IV hypersensitivity.

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ACKNOWLEDGEMENTS

This study was supported by the grants from the Health and Family Planning Commission of Hubei Province (No. 2013Z-Z01) and the Natural Science Foundation of Hubei Province of China (No. 2015CFA096).

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Authors and Affiliations

  1. Department of Pathogen Biology, College of Basic Medicine, Hubei University of Chinese Medicine, Wuhan, 430065, China

    Zhigang Wang & Hong Fan

  2. Department of Integrated Chinese Traditional and Western Medicine, Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology, Wuhan, 430030, China

    Zhe Chen

  3. Department of Anatomy, College of Basic Medicine, Hubei University of Chinese Medicine, Wuhan, 430065, China

    Tao Chen & Zhou Zheng

  4. College of Basic Medicine, Hubei University of Chinese Medicine, Wuhan, 430065, China

    Tao Yi

  5. Hubei Provincial Collaborative Innovation Center of Preventive Treatment by Acupuncture and Moxibustion, Hubei University of Chinese Medicine, 1 Huangjiahu West Road, Hongshan District, Wuhan, 430065, Hubei, China

    Zebin Chen

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  1. Zhigang Wang
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Correspondence to Zebin Chen.

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Wang, Z., Chen, Z., Chen, T. et al. Berberine Attenuates Inflammation Associated with Delayed-Type Hypersensitivity via Suppressing Th1 Response and Inhibiting Apoptosis. Inflammation 40, 221–231 (2017). https://doi.org/10.1007/s10753-016-0472-6

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