Effect and mechanism of ligustrazine on Th1/Th2 cytokines in a rat asthma model.
Ligustrazine is an alkaloid isolated from the rhizome of Chuanxiong (Ligusticum chuanxiong Hort), which is known to possess antioxidant, anti-inflammatory, anti-fibrosis and immunomodulative effects. It is used clinically to treat asthma as an assistant therapy of glucocorticoid. The purpose of this study was to explore the effects of intraperitoneal ligustrazine on Th1/Th2 cytokines in a rat asthma model and the underlying mechanism. SD rats were sensitized and challenged with ovalbumin (OVA) to establish an asthmatic model. Within 24 hours after the last ovalbumin challenge, changes in airway histology were observed. The concentrations of IL-4 and IFN-gamma in bronchoalveolar lavage fluid (BALF) were measured by enzyme linked immunosorbent assay (ELISA). The protein expressions of GATA-3 and T-bet in lung were measured by Western blot. The results showed that an increase of Th2 cytokine and an inhibition of Th1 cytokine were accompanied by an increased expression of GATA-3 protein and a decreased expression of T-bet protein in rat asthmatic airways compared to those in normal control group. Intraperitoneal ligustrazine administration could significantly lower the level of IL-4 in BALF and the expression of GATA-3 protein in lung and also increase the level of IFN-gamma and T-bet in asthmatic rats, resulting in a decreased percentage of eosinophils (EOS) in BALF and ameliorated airway inflammatory cell infiltration. In conclusion, ligustrazine inhibits OVA induced airway inflammation by modulating key master switches GATA-3 and T-bet that result in reversing the Th2 cytokine patterns in asthma.
Xiong
Liang
L
Key Lab of Pulmonary Diseases of Ministry of Health, Department of Respiratory Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Fang
Zheng-Yu
ZY
Tao
Xiao-Nan
XN
Bai
Ming
M
Feng
Gang
G
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001249:Asthma / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid; D004195:Disease Models, Animal; D004804:Eosinophils / Q000378:metabolism; D050990:GATA3 Transcription Factor / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism*; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D010047:Ovalbumin; D011719:Pyrazines / Q000494:pharmacology*; D051381:Rats; D020825:T-Box Domain Proteins / Q000378:metabolism*; D018417:Th1 Cells / Q000187:drug effects / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects / Q000378:metabolism; D000098815:T-bet Transcription Factor
D000893:Anti-Inflammatory Agents; D050990:GATA3 Transcription Factor; D011719:Pyrazines; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D015847:Interleukin-4; D007371:Interferon-gamma; D010047:Ovalbumin; C017953:tetramethylpyrazine