Feng-Yun Wang

Herbal prescription Chang'an II repairs intestinal mucosal barrier in rats with post-inflammation irritable bowel syndrome

Aim:The herbal prescription Changan II is derived from a classical TCM formula Tong-Xie-Yao-Fang for the treatment of liver-qi stagnation and spleen deficiency syndrome of irritable bowel syndrome (IBS). In this study we investigated the effects of Changan II on the intestinal mucosal immune barrier in a rat post-inflammation IBS (PI-IBS) model.Methods:A rat model of PI-IBS was established using a multi-stimulation paradigm including early postnatal sibling deprivation, bondage and intrarectal administration of TNBS. Four weeks after TNBS administration, the rats were treated with Changan II (2.85, 5.71 and 11.42 g·kg−1·d−1, ig) for 14 d. Intestinal sensitivity was assessed based on the abdominal withdrawal reflex (AWR) scores and fecal water content. Open field test and two-bottle sucrose intake test were used to evaluate the behavioral changes. CD4+ and CD8+ cells were counted and IL-1β and IL-4 levels were measured in intestinal mucosa. Transmission electron microscopy was used to evaluate ultrastructural changes of the intestinal mucosal barrier.Results:PI-IBS model rats showed significantly increased AWR reactivity and fecal water content, and decreased locomotor activity and sucrose intake. Changan II treatment not only reduced AWR reactivity and fecal water content, but also suppressed the anxiety and depressive behaviors. Ultrastructural study revealed that the gut mucosal barrier function was severely damaged in PI-IBS model rats, whereas Changan II treatment relieved intestinal mucosal inflammation and repaired the gut mucosal barrier. Furthermore, PI-IBS model rats showed a significantly reduced CD4+/CD8+ cell ratio in lamina propria and submucosa, and increased IL-1β and reduced IL-4 expression in intestinal mucosa, whereas Changan II treatment reversed PI-IBS-induced changes in CD4+/CD8+ cell ratio and expression of IL-1β and IL-4.Conclusion:Changan II treatment protects the intestinal mucosa against PI-IBS through anti-inflammatory, immunomodulatory and anti-anxiety effects.

Clinical practice guideline of Chinese medicine for chronic gastritis

Chronic gastritis (CG) is an inflammatory condition of the gastric mucosa, induced by various causes. A commonly-seen disease in clinical practice, it is found in about 80%-90% of patients undergoing gastroscopic examination. The prevalence rate in the general population remains unclear. It is generally considered that its incidence rate accords with Helicobacter. pylori infection rate and the prevalence of CG is 30%-80% in China. Possible etiological factors include H. pylori infection, smoking, drinking alcohol, food allergies, duodenal juice reflux, drug-induced injuries, heredity, immunity, and radiation. (1-8) Some patients with CG have no obvious clinical manifestations, and symptomatic patients mainly show symptoms of non-specific dyspepsia. In H. pylori related CG, the disease will persist unless the H. pylori infection is eradicated. There is a higher risk of gastric cancer if chronic atrophic gastritis (CAG) is accompanied by intestinal metaplasia or dysplasia; it is commonly believed that the canceration rate of atrophic gastritis is 0.5%-1% annually. (9)

A randomized, controlled, double-blinded and double-dummy trial of the effect of Tongjiang Granule (通降颗粒) on the nonerosive reflux disease of and Gan (肝)-Wei (胃) incoordination syndrome

ObjectiveTo assess the effectiveness of Tongjiang Granule (TJG, 通降颗粒) on the patients with nonerosive reflux disease (NERD) of Gan (肝)-Wei (胃) incoordination syndrome, its impact on their quality of life, and its safety.MethodA randomized, controlled, double-blinded, and double-dummy method was adopted in the trial. There were 120 NERD patients enrolled in the study and randomly divided into the experiment and control groups, each with 60 patients; drugs were distributed according to the drug number by patients’ inclusion sequences. In the experiment group, patients were given TJG 10 g and mosapride citrate dummy 5 mg three times a day, and in the control group, patients were given mosapride citrate 5 mg and TJG dummy 10 g three times a day. The treatment courses of both groups were 4 weeks.ResultsAmong 120 included patients, 112 were screened for full analysis set (FAS), and 105 were screened per-protocol set (PPS). The results were as follows: (1) the improvement of total scores of symptom in the experiment group (0–4 week) were 15.93±7.88 scores by FAS and 16.22 ±7.75 scores by PPS, and they were 10.43±10.16 scores and 10.79±10.27 scores in the control group, respectively. The 95% CI of net scores improvement between the two groups were 2.10–8.90 scores and 1.92–8.94 scores in FAS and PPS; it was significantly better in the experiment group than that in the control group (P<0.05). (2) The improvement of scores of major symptom in the experiment group (0–4 week) were 10.68±5.35 by FAS and 10.89±5.29 by PPS and 7.40±7.41 and 7.60±7.46 in the control group, respectively. The 95% CI of net scores improvement in the two groups were 0.85–5.71 and 0.71–5.69 in FAS and PPS separately, and the improvement in the experiment group was significantly better than that in the control group (P<0.05). (3) The total effective rates were 86.0% and 61.8% in the experiment and the control group separately, and the Ridit analysis results showed that it was better in the experiment group (P<0.05). (4) The improvement quality of life in the domain of physical functioning and general health in the experiment group was better than that in the control group (P<0.05). (5) One case of experiment group caught a cold and recovered in six days without drug suspension. No adverse event was found in the other cases. There was no meaningful safety examination indices change in pretreatment and posttreatment periods in both groups.ConclusionTJG showed a definite effect on the treatment of NERD with Gan-Wei incoordination syndrome, and it could improve the quality of life of NERD patient without obvious toxic and side effects.

Randomized double-blind clinical trial of Moluodan (摩罗丹) for the treatment of chronic atrophic gastritis with dysplasia

ObjectiveTo assess the efficacy and safety of Moluodan (摩罗丹) in treating dysplasia in chronic atrophic gastritis (CAG) patients.MethodsThis was a multi-centered, double-blind, randomized controlled trial. The total of 196 subjects were assigned to receive either Moluodan or folic acid in a 2:1 ratio by blocked randomization. Mucosa marking targeting biopsy (MTB) was used to insure the accuracy and consistency between baseline and after 6-month treatment. Primary outcomes were histological score, response rate of pathological lesions and dysplasia disappearance rate. Secondary endpoints included gastroscopic findings, clinical symptom and patient reported outcome (PRO) instrument.ResultsDysplasia score decreased in Moluodan group (P =0.002), significance was found between groups (P =0.045). Dysplasia disappearance rates were 24.6% and 15.2% in Moluodan and folic acid groups respectively, no significant differences were found (P =0.127). The response rate of atrophy and intestinal metaplasia were 34.6% and 23.0% in Moluodan group, 24.3% and 13.6% in folic acid group. Moluodan could improve erythema (P =0.044), and bile reflux (P =0.059), no significance between groups. Moluodan was better than folic acid in improving epigastric pain, epigastric suffocation, belching and decreased appetite (P <0.05), with symptom disappearance rates of 37% to 83%.ConclusionsMoluodan improved dysplasia score in histopathology, and erythema and bile reflux score in endoscopy, and superior to folic acid in improving epigastric pain, epigastric suffocation, belching and decreased appetite. [ChiCTR-TRC-00000169]

Therapeutic Effect of Chang’an I Recipe (肠安I号方) on irritable bowel syndrome with diarrhea: A multicenter randomized double-blind placebo-controlled clinical trial

ObjectiveTo evaluate the efficacy and safety of Chinese medicine (CM) decoction Chang’an I Recipe (肠安 I 号方) in the treatment of irritable bowel syndrome with diarrhea (IBS-D).MethodA multicenter, randomized, double-blind, placebo-controlled clinical trial was designed. Based on the order of inclusion, the IBS-D patients were randomly assigned to the treatment group or the placebo control group, administrated with Chang’an I Recipe or placebo, 150 mL/bag, 3 times daily, for 8 weeks. The primary indices of efficacy included the effective rates of IBS symptom severity score (IBS-SSS) and the differences in adequate relief (AR) responder; the secondary indexes of efficacy included the changes in scores of the IBS Quality of Life (IBS-QOL) and Hospital Anxiety and Depression (HAD) scales. The safety indices included adverse events and related laboratory tests.ResultsA total of 216 patients were included, with 109 in the treatment group and 107 in the control group, and finally 206 were included in the full analysis set (FAS), 191 were included in the per protocol set (PPS). In FAS, the total effective rate was 67.6% and 40.2% for the treatment and control groups, respectively, with 95% confidence interval (CI) for difference in the effective rates between the two groups of 14.4%–40.2%; while in PPS, the total effective rate was 71.3% and 41.2% for the treatment and control groups, respectively (95% CI 16.6%–43.4%). The consistent conclusions of FAS and PPS showed a better efficacy in the treatment group. Both FAS and PPS showed higher AR responder in the treatment group (FAS: 59.6% vs. 35.5%; PPS: 62.8% vs. 38.1%). As for IBS-QOL, the total score and scores in various dimensions of IBS-QOL were not significantly different between the two groups (P>0.05). Both anxiety and depression scales of HAD were not significantly different between the two groups (P>0.05). No adverse events or laboratory abnormalities were found to be obviously related to the tested drugs or clinically significant.ConclusionChang’an I Recipe was more effective than placebo in the treatment of IBS-D, with no obvious adverse reactions. (No.ChiCTR-TRC-09000328)

PTRF suppresses the progression of colorectal cancers

As a key component of caveolae structure on the plasma membrane, accumulated evidence has suggested that Polymerase I and Transcript Release Factor (PTRF) plays a pivotal role in suppressing the progression of human malignances. However, the function of PTRF in the development of colorectal cancers is still unclear. Here we report that the expression of PTRF is significantly reduced in tumor tissues derived from human patients with colorectal cancers, and that the downregulation of PTRF correlates to the advanced stage of the disease. In addition, we found that the expression of PTRF negatively regulates the tumorigenic activities of colorectal cell lines (Colo320, HT29 and CaCo2). Furthermore, ectopic PTRF expression caused significant suppression of cellular proliferation, and anchorage-independent colony growth of Colo320 cells, which have the lowest expression level of PTRF in the three studied cell lines. Meanwhile, shRNA mediated knockdown of PTRF in CaCo2 cells significantly promoted cellular proliferation and anchorage-independent colony growth. In addition, in vivo assays further revealed that tumor growth was significantly inhibited in xenografts with ectopic PTRF expression as compared to untreated Colo320 cells, but was markedly enhanced in PTRF knockdown CaCo2 cells. Biochemical studies revealed that overexpression of PTRF led to the suppression of the AKT/mTOR pathway, as evidenced by reduced phosphorylation of AKT, mTOR, and downstream MMP-9. Thus, these findings, for the first time, demonstrated that PTRF inhibits the tumorigenesis of colorectal cancers and that it might serve as a potential therapeutic target for human colon cancer patients.

Shen-ling-bai-zhu-san, a spleen-tonifying Chinese herbal formula, alleviates lactose-induced chronic diarrhea in rats

ETHNOPHARMACOLOGICAL RELEVANCEnShen-ling-bai-zhu-san (SLBZS) was firstly documented in ancient Chinese medical works Tai Ping Hui Min He Ji Ju Fang in Song-dynasty. It has been widely used for treating gastrointestinal disorders such as diarrhea with poor appetite for about 900 years. The present study is to observe the effects of SLBZS on high lactose diet-induced chronic diarrhea.nnnMATERIALS AND METHODSnRats were subjected to a high lactose diet to induce chronic diarrhea, which were then administrated with SLBZS or smecta. General symptom, body weight, food consumption, water intake and fecal fluid content were recorded every day. The intestinal absorption function was determined by d-xylose uptake assay. The ultrastructures of intestine segments including jejunum, ileum, proximal and distal colon were observed by transmission electron microscopy. Additionally, sodium transport proteins including γ-epithelial sodium channel (ENAC-γ) and sodium/potassium-transporting ATPase subunit alpha-1 (ATP1A1) in distal colon were detected by immunohistochemistry and western blotting.nnnRESULTSnDiarrheal rats produced watery or loose, sticky feces, and presented inactiveness and grouping. A high lactose diet caused a significant decline in body weight, serum d-xylose level as well as food consumption rather than water intake. In contrast, general symptoms were improved to a certain extent and body weight loss was alleviated in the rats treated by SLBZS for one week. Fecal fluid content in diarrheal rats treated by SLBZS presented a gradual decrease trend with about 55% in the end, which was significantly less than the model group with about 81%. Meanwhile, SLBZS significantly improved the serum d-xylose level and reversed abnormal changes of tight junctions and microvilli in intestine. Additionally, SLBZS significantly modulated the abnormal expressions of ENAC-γ and ATP1A1 in distal colon of diarrheal rats.nnnCONCLUSIONSnThese findings suggested that SLBZS exhibited ameliorating effects against lactose-induced diarrhea, which might be attributed to its modulations on intestinal absorption function as well as mucosal ultrastructure.

Efficacy and safety of Xiangsha Liujunzi granules for functional dyspepsia: A multi-center randomized double-blind placebo-controlled clinical study

AIM To assess the efficacy and safety of a Chinese herbal medicine (CHM), Xiangsha Liujunzi granules, in the treatment of patients with functional dyspepsia (FD). METHODS We performed a randomized, double-blind, placebo-controlled trial with patients from three centers. Two hundred and sixteen subjects diagnosed with FD according to ROME III criteria and confirmed by upper gastrointestinal endoscopy and spleen-deficiency and Qi-stagnation syndrome were selected to receive Xiangsha Liujunzi granules or placebo for 4 wk in a 2:1 ratio by blocked randomization. The subjects also received follow-up after the 4-wk intervention. Herbal or placebo granules were dissolved in 300 mL of water. Participants in both groups were administered 130 mL (45 °C) three times a day. Participants were evaluated prior to and following 4 wk of the intervention in terms of changes in the postprandial discomfort severity scale (PDSS) score, clinical global impression (CGI) scale score, hospital anxiety and depression scale (HADS) score, traditional Chinese medicine symptoms score (SS), scores of various domains of the 36-item short form health survey (SF-36), gastric emptying (GE) and any observed adverse effects. RESULTS Compared with the placebo group, patients in the CHM group showed significant improvements in the scores of PDSS, HADS, SS, SF-36 and CGI scale (P < 0.05 or P < 0.01). They also showed the amelioration in the GE rates of the proximal stomach and distal stomach (P < 0.05 or P < 0.01). CONCLUSION Xiangsha Liujunzi granules offered significant symptomatic improvement in patients with FD.

The Effect of Tong-Xie-Yao-Fang on Intestinal Mucosal Mast Cells in Postinfectious Irritable Bowel Syndrome Rats

Objective. To investigate the effects of Tong-Xie-Yao-Fang (TXYF) on intestinal mucosal mast cells in rats with postinfectious irritable bowel syndrome (PI-IBS). Design. PI-IBS rat models were established using a multistimulation paradigm. Then, rats were treated with TXYF intragastrically at doses of 2.5, 5.0, and 10.0 g·kg−1·d−1 for 14 days, respectively. Intestinal sensitivity was assessed based on abdominal withdrawal reflex (AWR) scores and fecal water content (FWC). Mast cell counts and the immunofluorescence of tryptase and c-Fos in intestinal mucosa were measured; and serum IL-1β, TNF-α, and histamine levels were determined. Results. AWR reactivity and FWC which were significantly increased could be observed in PI-IBS rats. Remarkably increased mast cell activation ratio in intestinal mucosa, together with increased serum TNF-α and histamine levels, could also be seen in PI-IBS rats; furthermore, PI-IBS-induced changes in mast cell activation and level of serum TNF-α and histamine could be reversed by TXYF treatment. Meanwhile, tryptase and c-Fos expression were also downregulated. Conclusion. TXYF improves PI-IBS symptoms by alleviating behavioral hyperalgesia and antidiarrhea, the underlying mechanism of which involves the inhibitory effects of TXYF on activating mucosal mast cells, downregulating tryptase and c-Fos expression, and reducing serum TNF-α and histamine levels.

A preparation model of Chinese medicine decoction placebo

Chinese medicine (CM) decoction placebo is one of the key factors restricting the placebo-controlled clinical trial of CM. In this article, based on the analysis of the diffificulties in preparing CM placebo, the production requirements for placebo were put forward. Moreover, in accordance with clinical practices, a production method and evaluation process of CM decoction placebo was proposed, to provide a reference for clinical research.