Pien Tze Huang ameliorates DSS-induced colonic inflammation in a mouse colitis model through inhibition of the IL-6/STAT3 pathway

摘要

Intcrleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) pathway plays essential roles in the development of inflammatory diseases including ulcerative colitis (UC). Therefore, suppression of IL-6/STAT3 signaling provides a promising therapeutic strategy in UC. Pien Tze Huang (PZH), a well-known traditional Chinese formula, has been used in China and Southeast Asia for centuries as a folk remedy for various inflammatory diseases. However, the molecular mechanisms of its anti-inflammatory effects remain to be elucidated. In the present study, we generated a mouse colitis model by using dextran sulfate sodium (DSS) and evaluated the therapeutic efficacy of PZH against UC by observing the clinical manifestations. We found that PZH obviously alleviated DSS-induced colitis symptoms, including body weight loss, rectal bleeding and stool consistency. In addition, administration of PZH profoundly prevented DSS-induced colon shortening, and ameliorated colonic histopathological changes such as mucosal ulceration, infiltration of inflammatory cells, crypt distortion and hyperplastic epithelium. Moreover, PZH markedly inhibited the serum level of the inflammatory biomarker serum amylase A (SAA) in UC mice. Furthermore, PZH treatment significantly inhibited DSS-induced expression of IL-6 in colon tissues. Finally, the increased phosphorylation level of STAT3, induced either by DSS in experimental mice or by IL-6 in the differentiated human colorectal carcinoma cells, was significantly suppressed by PZH. These results suggest that the inhibition of IL-6/STAT3 signaling is a potential mechanism by which PZH is used in the treatment of UC.