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

Abstract

Interleukin‑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.

IL‑6/STAT3 signaling pathway regulates the proliferation and damage of intestinal epithelial cells in patients with ulcerative colitis via H3K27ac

“…The IL-6/STAT3 signaling pathway is important in intestinal inflammation and colon cancer. For example, inhibition of the IL-6/STAT3 signaling pathway improves intestinal injury in acute enteritis (37). In addition, the IL-6/STAT3/suppressor of cytokine signaling-3 (SOCS3) signaling pathway plays an important role in the carcinogenesis of enteritis (38).…”

Inflammatory bowel disease: an overview of Chinese herbal medicine formula-based treatment

“…Gegen Qinlian Decoction and Huanglian Jiedu Decoction reduce inflammation by inhibiting JAK2/STAT3, decrease inflammation by inhibiting JAK2/STAT3 signaling, and has a protective effect on UC [ 45 , 83 ]. Qingre Zaoshi Liangxue Decoction, Pien Tze Huang, and Baitouweng Decoction significantly improved the inflammatory symptoms in mice with acute colitis, and the latent mechanism may be related to various signaling pathways, including regulation of gut microbiota and inflammatory signaling pathways, such as IL-6/STAT3 [ 46 , 84 , 85 ].…”

Pien Tze Huang (PZH) as a Multifunction Medicinal Agent in Traditional Chinese Medicine (TCM): a review on cellular, molecular and physiological mechanisms

“…Actually, administration of PZH has potentially prevented DSS-induced colon shortening, as well as ameliorating colonic histopathological changes (such as mucosal ulceration), infiltration of inflammatory cells, crypt distortion and diminishing hyperplastic epithelium. Moreover, PZH can markedly inhibit the serum levels of the inflammatory biomarker serum amylase A (SAA) in UC mice, probably through inhibiting IL-6/STAT3 cascades [118].…”