Berberine Attenuates Inflammation Associated with Delayed-Type Hypersensitivity via Suppressing Th1 Response and Inhibiting Apoptosis.
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.
Department of Pathogen Biology, College of Basic Medicine, Hubei University of Chinese Medicine, Wuhan, 430065, China.
Zhigang
Z
Wang
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
Z
Chen
Department of Anatomy, College of Basic Medicine, Hubei University of Chinese Medicine, Wuhan, 430065, China.
Tao
T
Chen
College of Basic Medicine, Hubei University of Chinese Medicine, Wuhan, 430065, China.
Tao
T
Yi
Department of Anatomy, College of Basic Medicine, Hubei University of Chinese Medicine, Wuhan, 430065, China.
Zhou
Z
Zheng
Department of Pathogen Biology, College of Basic Medicine, Hubei University of Chinese Medicine, Wuhan, 430065, China.
Hong
H
Fan
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. chenzebin-hbtcm@outlook.com.
Zebin
Z
Chen
D000818:Animals; D000893:Anti-Inflammatory Agents; D017209:Apoptosis / Q000187:drug effects*; D001599:Berberine / Q000494:pharmacology* / Q000627:therapeutic use; D002454:Cell Differentiation / Q000187:drug effects; D016207:Cytokines / Q000187:drug effects; D006968:Hypersensitivity, Delayed / Q000473:pathology*; D007166:Immunosuppressive Agents; D007249:Inflammation / Q000188:drug therapy*; D051379:Mice; D010047:Ovalbumin; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D007166:Immunosuppressive Agents; D001599:Berberine; D010047:Ovalbumin
Th1 response; apoptosis; berberine; delayed-type hypersensitivity; inflammation