Jianpi-Qingchang decoction alleviates ulcerative colitis by modulating endoplasmic reticulum stress-related autophagy in intestinal epithelial cells.

Endoplasmic reticulum stress (ERS)-related autophagy is involved in the occurrence and development of ulcerative colitis (UC). Therefore, regulating ERS-related autophagy is a potential therapeutic target for the treatment of UC. Jianpi-Qingchang (JPQC) decoction, consisting of nine Chinese herbal medicines, is used to treat patients with UC. However, its mechanism of action has not been completely elucidated. Here, we aimed to reveal the therapeutic effects and mechanisms of JPQC in UC. We established a colitis model using dextran sulfate sodium (DSS) and an ERS model using thapsigargin (Tg) and administered JPQC. We systematically examined ERS-related autophagy associated protein expression, inflammatory cytokines, apoptotic cells, and autophagic flux. Moreover, the cellular ultrastructure was observed via transmission electron microscopy (TEM). We found that JPQC reduced disease activity index (DAI) scores, counteracted colonic tissue damage, decreased the number of autophagosomes, inhibited proinflammatory cytokines, enhanced anti-inflammatory cytokines, and dampened ERS-related autophagy associated protein gene expression.

Clinical Efficacy of Jianpi Qingchang Decoction in Treating Patients with Spleen Deficiency Damp-heat Hormone-dependent Ulcerative Colitis / 中国实验方剂学杂志

Objective::To observe the effect of Jianpi Qingchang decoction on hormone withdrawal in patients with hormone-dependent spleen deficiency damp-heat ulcerative colitis. Method::The 60 patients with hormone-dependent ulcerative colitis with spleen deficiency and damp-heat were selected and collected from the outpatient department and the inpatient department of Longhua Hospital, Shanghai University of Traditional Chinese Medicine(TCM) between April 1, 2012 and January 31, 2014.All of patients in two groups were treated with standard hormone reduction method. The control group was given orally Bupi Yichang pills, 6 g/time, 3 times/day, and the experimental group was given orally Jianpi Qingchang recipe, 300 mL water decoction, 1 dose/d, 2 times/d. All of the patients received continuous treatment for 3 months. After treatment, disease activity index, mucosal healing evaluation, curative effect changes of TCM syndromes and changes of inflammatory factors in the two groups were observed. Result::Compared with before treatment, the two groups of Mayo scores after treatment were significantly reduced (P<0.01), and the experimental group was reduced more significantly than the control group (P<0.01). After treatment, 66.67%of patients in experimental group were in remission, and 13.33%of patients in control group were in remission, with statistically significant differences between two groups (P<0.01). After treatment, the healing rate of the control group was 46.67%, while that of the experimental group was 70.0%, with statistically significant differences (P<0.01). After treatment, the effective rate of TCM syndromes in control group was 80.0%, while that in experimental group was 96.67%, with statistically significant differences (P<0.01). Compared with control group before treatment, the levels of IL-1 in both groups were decreased (P<0.05), while the levels of IL-6 and IL-10 were increased (P<0.05). Compared with control group after treatment, the changes in experimental group were significantly better than those in control group (P<0.05). Conclusion::Jianpi Qingchang decoction can reduce the index of disease activity in patients with hormone-dependent ulcerative colitis due to spleen deficiency and dampness-heat, promote mucosal healing and improve the curative effect of TCM symptoms, and thus is worthy of clinical promotion.

Clinical Efficacy of Jianpi Qingchang Decoction in Treating Patients with Spleen Deficiency Damp-heat Hormone-dependent Ulcerative Colitis / 中国实验方剂学杂志

Objective:To observe the clinical efficacy of Jianpi Qingchang decoction in the treatment of spleen deficiency and damp-heat hormone-dependent ulcerative colitis and explore its possible target. Method:A total of 60 patients with spleen deficiency and damp-heat hormone-dependent ulcerative colitis were selected and collected from the outpatient department and the inpatient department of Longhua Hospital affiliated to Shanghai University of Chinese Medicine on April 31, 2012.Two groups were given the basic therapy of prednisone, and control group received orally bolus for spleen and spleen and intestines, 6 g/time, 3 times/d. The treatment continued for three months. The experimental group was given orally Jianpi Qingchang decoction, 1 dose per day, and 300 mL water decoction, 150 mL each time, 2 times/d, and took at different temperatures in the morning and evening. The treatment continued for three months. After treatment, changes in intestinal symptom score, traditional Chinese medicine (TCM) syndrome score and endoscopic score of two groups were observed. Result:Compared with before treatment, the symptom scores of diarrhea, mucous purulent in control group were significantly reduced after treatment (PPPPPPPPPConclusion:Jianpi Qingchang decoction can effectively improve mucous purulent stool and diarrhea symptoms in patients with spleen deficiency and damp-heat hormone-dependent ulcerative colitis, and reduce TCM syndrome score and endoscopic score, and thus is worthy of clinical reference and promotion.

Jianpi Qingchang decoction regulates intestinal motility of dextran sulfate sodium-induced colitis through reducing autophagy of interstitial cells of Cajal.

AIM: To investigate the underlying effect of Jianpi Qingchang decoction (JQD) regulating intestinal motility of dextran sulfate sodium (DSS)-induced colitis in mice. METHODS: C57BL/6 mice were randomly divided into four groups: the control group, the DSS group, the JQD group, and the 5-aminosalicylic acid group. Except for the control group, colitis was induced in other groups by giving distilled water containing 5% DSS. Seven days after modeling, the mice were administered corresponding drugs intragastrically. The mice were sacrificed on the 15th day. The disease activity index, macroscopic and histopathologic lesions, and ultrastructure of colon interstitial cells of Cajal (ICC) were observed. The levels of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1ß, IL-10 and interferon gamma (IFN-γ), the expression of nuclear factor-kappa B (NF-κB) p65, c-kit, microtubule-associated protein 1 light chain 3 (LC3-II) and Beclin-l mRNA, and the colonic smooth muscle tension were assessed. RESULTS: Acute inflammation occurred in the mice administered DSS. Compared with the control group, the levels of IL-1ß, TNF-α, IL-10 and IFN-γ, the expression of LC3-II, Beclin-1 and NF-κB p65 mRNA, and the contractile frequency increased (P < 0.05), the expression of c-kit mRNA and the colonic smooth muscle contractile amplitude decreased in the DSS group (P < 0.05). Compared with the DSS group, the levels of IL-10 and IFN-γ, the expression of c-kit mRNA, and the colonic smooth muscle contractile amplitude increased (P < 0.05), the levels of TNF-α and IL-1ß, the expression of LC3-II, Beclin-1 and NF-κB p65 mRNA, and the contractile frequency decreased in the JQD group (P < 0.05). CONCLUSION: JQD can regulate the intestinal motility of DSS-induced colitis in mice through suppressing intestinal inflammatory cascade reaction, reducing autophagy of ICC, and regulating the network path of ICC/smooth muscle cells.

Jianpi Qingchang decoction alleviates ulcerative colitis by inhibiting nuclear factor-κB activation.

AIM: To investigate the therapeutic effect of Jianpi Qingchang decoction (JPQCD) on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice. METHODS: C57BL/c mice were injected intragastrically with 5% DSS instead of drinking water for 7 d, and their body weight, diarrhea severity and fecal bleeding were monitored, while the mice in the control group were treated with standard drinking water, without DSS. After 7 d, the DSS drinking water was changed to normal water and the DSS group continued with DSS water. The control and DSS groups were given normal saline by intragastric injection. The 5-aminosalicylic acid (5-ASA) group was treated orally with 5-ASA at a dose of 100 mg/kg daily. The JPQCD group was treated orally with JPQCD at a dose of 17.1 g/kg daily. On day 14, the colon length was measured, the colorectal histopathological damage score was assessed, and protein levels of interleukin (IL)-1ß, IL-8 and tumor necrosis factor-alpha (TNF-α) in colon supernatants were measured by enzyme-linked immunosorbent assay. mRNA expression of IL-1ß, IL-8, TNF-α and nuclear factor-kappa B (NF-κB) was detected by real-time quantitative polymerase chain reaction. Western blotting was used to detect the protein expression of NF-κB and inhibitor of kappa B. RESULTS: Acute inflammation occurred in the mice administered DSS, including the symptoms of losing body weight, loose feces/watery diarrhea and presence of fecal blood; all these symptoms worsened at 7 d. The colons of mice treated with DSS were assessed by histological examination, and the results confirmed that acute inflammation had occurred, as evidenced by loss of colonic mucosa and chronic inflammatory cell infiltration, and these features extended into the deeper layer of the colon walls. The expression levels of IL-1ß, IL-8 and TNF-α in the DSS group were higher than those in the control group (P < 0.05), and the expression levels of IL-1ß, IL-8 and TNF-α in the JPQCD and 5-ASA groups were lower than those in the DSS group after treating with JPQCD and 5-ASA. Comparing with the DSS group, the mRNA level of IL-1ß, IL-8, TNF-α and NF-κB was significantly reduced by 5-ASA and JPQCD. The difference between JPQCD and 5-ASA groups was not statistically significant (P > 0.05). Comparing with the DSS group, due to using JPQCD and 5-ASA, significant suppression of activation in DSS-induced NF-κB and increased phosphorylation of IκB in mice with experimental colitis occurred (P < 0.05). The difference between the JPQCD group and the 5-ASA group was not statistically significant (P > 0.05). CONCLUSION: Activation of the NF-κB signaling pathway is inhibited by JPQCD, which shows the potential mechanism by which JPQCD treats UC.