Effect of Sishen Pill on Memory T Cells From Experimental Colitis Induced by Dextran Sulfate Sodium

Abstract

Immune memory has a protective effect on the human body, but abnormal immune memory is closely related to the occurrence and development of autoimmune diseases including inflammatory bowel disease (IBD). Sishen Pill (SSP) is a classic prescription of traditional Chinese medicine, which is often used to treat chronic colitis, but it is not clear whether SSP can alleviate experimental colitis by remodeling immune memory. In the present study, the therapeutic effect of SSP on chronic colitis induced by dextran sulfate sodium (DSS) was evaluated by colonic length, colonic weight index, macroscopic and microscopic scores, and pathological observation. The cytokine levels were tested by enzyme-linked immunosorbent assay (ELISA); the percentages of central memory T (Tcm) and effector memory T (Tem) cells were analyze\d by flow cytometry; and activation of phosphoinositide 3-kinase (PI3K)/Akt signaling proteins was measured by western blotting. After 7-days' treatment, SSP alleviated DSS-induced colitis, which was demonstrated by decreased colonic weight index, colonic weight, histopathological injury scores, restored colonic length, gradual recovery of colonic mucosa, and lower levels of interleukin (IL)-2, IL-7, IL-12, and IL-15, while SSP increased IL-10 expression. SSP obviously regulated the quantity and subpopulation of Tcm and Tem cells. Furthermore, SSP markedly inhibited activation of PI3K, Akt, phospho-Akt, Id2, T-bet, forkhead box O3a, Noxa, and C-myc proteins in the PI3K/Akt signaling pathway and activated Rictor, Raptor, tuberous sclerosis complex (TSC)1, TSC2, phospho-AMPactivated kinase (AMPK)-a, AMPK-a, eukaryotic translation initiation factor 4E-binding protein 2, kinesin family member 2a, and 70-kDa ribosomal protein S6 kinase. These results indicate that SSP effectively controls Tem cells in the peripheral blood to relieve experimental colitis induced by DSS, which were potentially related with inhibiting the PI3K/Akt signaling pathway.

Curcumin Regulated the Homeostasis of Memory T Cell and Ameliorated Dextran Sulfate Sodium-Induced Experimental Colitis

“…In addition, colonic histopathological damage scores were higher in the DSS group than in the normal group (Figure 1F). This was consistent with previous reports (Ge et al, 2020), suggesting that the DSSinduced experimental colitis was successfully replicated.…”

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

“…Zuojin Pill can modulate the crosstalk between intestinal microbes and Treg cells to attenuate DSS-induced colitis through PI3K/Akt signaling pathway [ 76 ]. Sishen Pill alleviates DSS-induced colitis, which may be related to inhibiting the PI3K/Akt signaling pathway [ 77 ]. Xianglian Pill can block the activation of the PI3K/Akt/mTOR pathway, inhibit the secretion of pro-inflammatory cytokines, and repair the dysfunction of the intestinal epithelial barrier to enhance autophagy [ 78 ].…”

Sishen Pill Regulates Memory T Cells in Mice with Colitis via JAK/STAT 5 Signaling Pathway

“…(Pharmacopoeia of China (2015)), which were prepared into pills according to the dose ratio (100g, 200g, 400g, 200g, 200g, and 200g, ratio:1:2:4:2:2:2, respectively). The main active ingredients were measured by High-Performance Liquid Chromatography (HLPC) according to a previously described approach [9]. ASA (Mesalazine enteric-coated tablets) (batch number 181003) was obtained from Sun ower Pharmaceutical Group Jiamusi Luling Pharmaceutical Co., Ltd. (Heilongjiang, China).…”