Si Shen Wan Inhibits mRNA Expression of Apoptosis-Related Molecules in p38 MAPK Signal Pathway in Mice with Colitis

Abstract

Si Shen Wan (SSW) is used to effectively treat ulcerative colitis (UC) as a formula of traditional Chinese medicine. To explore the mechanism of SSW-inhibited apoptosis of colonic epithelial cell, the study observed mRNA expression of apoptosis-related molecules in p38 MAPK signal pathway in colonic mucosa in colitis mice treated with SSW. Experimental colitis was induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) in mice; meanwhile, the mice were administrated daily either SSW (5 g/kg) or p38 MAPK inhibitor (2 mg/kg) or vehicle (physiological saline) for 10 days. While microscopical evaluation was observed, apoptosis rate of colonic epithelial cell and mRNA expression of apoptosis-related molecules were tested. Compared with colitis mice without treatment, SSW alleviated colonic mucosal injuries and decreased apoptosis rate of colonic epithelial cell, while the mRNA expressions of p38 MAPK, p53, caspase-3, c-jun, c-fos, Bax, and TNF-α were decreased in the colonic mucosa in colitis mice treated with SSW, and Bcl-2 mRNA and the ratio of Bcl-2/Bax were increased. The present study demonstrated that SSW inhibited mRNA expression of apoptosis-related molecules in p38 MAPK signal pathway to downregulate colonic epithelial cells apoptosis in colonic mucosa in mice with colitis.

Geraniol ameliorates TNBS-induced colitis: Involvement of Wnt/β-catenin, p38MAPK, NFκB, and PPARγ signaling pathways

“…In the present work, TNBS boosted the apoptotic marker caspase-3, a finding that coincides with the results of previous studies [50,62]. Increased caspase-3 may be accredited, partly, to the activation of p38MAPK, where several studies proved that p38MAPK activation is responsible for apoptosis of colonic epithelial cells in UC [50]. Moreover, TNBS-induced caspase-3 may be responsible for the downregulation of PPARγ, where Guilherme et al [63] have evidenced that caspase-3 cleaves PPARγ protein and disrupts its nuclear localization.…”

“…In the present work, TNBS boosted the apoptotic marker caspase-3, a finding that coincides with the results of previous studies [50,62]. Increased caspase-3 may be accredited, partly, to the activation of p38MAPK, where several studies proved that p38MAPK activation is responsible for apoptosis of colonic epithelial cells in UC [50].…”

“…Moreover, and in accordance with our results, it was stated that colitis induces the nuclear translocation of β-catenin [10] and that β-catenin can promote colitis and colon cancer through imprinting proinflammatory properties in T cells [51]. As a correlation between β-catenin and proinflammatory mediators, β-catenin can be considered as a transcriptional coactivator that provides NFκB p50 subunit leading finally to induction of proinflammatory genes [50]. In a vicious cycle, the activated p38MAPK may be accredited to the increased production of reactive oxygen species, which activate diverse downstream signaling pathways, including NFκB [17].…”

Si Shen Wan Regulates Phospholipase Cγ-1 and PI3K/Akt Signal in Colonic Mucosa from Rats with Colitis

“…According to calculating by body surface area between human and rat, we designed dosage of SSW and projected the experimental protocol on the basis of our previous studies [ 7 – 9 ]. Ten animals were in each group.…”

“…Furthermore, we observed that the antiapoptotic effect of SSW was probably realized by inhibiting mRNA expression of apoptosis-related molecules in p38 MAPK signal pathway. All results had demonstrated that SSW effectively treated colitis by inhibiting excessive apoptosis of IECs [ 7 – 9 ].…”