Qingre Xingyu recipe exerts inhibiting effects on ulcerative colitis development by inhibiting TNFα/NLRP3/Caspase-1/IL-1ß pathway and macrophage M1 polarization.

As a chronic inflammatory bowel disease, ulcerative colitis (UC) imposes a significant burden on public healthcare worldwide due to its increasing morbidity. Chinese medicines are regarded as potent therapeutic agents for UC treatment with minimal side effects. In the present study, we sought to determine the novel role of a traditional medicine Qingre Xingyu (QRXY) recipe in the development of UC and aimed to contribute to the currently available knowledge about UC by exploring the downstream mechanism of QRXY recipe in UC. Mouse models of UC were established by injections with dextran sulphate sodium (DSS), where the expression of tumor necrosis factor-alpha (TNFα), NLR family pyrin domain containing 3 (NLRP3), and interleukin-1ß (IL-1ß) was determined followed by an analysis of their interactions. The DSS-treated NLRP3 knockout (-/-) Caco-2 cell model was successfully constructed. The in vitro and in vivo effects of the QRXY recipe on UC were investigated with the determination of disease activity index (DAI), histopathological scores, transepithelial electrical resistance, FITC-dextran, as well as cell proliferation and apoptosis. In vivo and in vitro experiments indicated that the QRXY recipe reduced the degree of intestinal mucosal injury of UC mice and functional damage of DSS-induced Caco-2 cells by inhibition of the TNFα/NLRP3/caspase-1/IL-1ß pathway and M1 polarization of macrophages, and TNFα overexpression or NLRP3 knockdown could counterweigh the therapeutic effects of QRXY recipe. To conclude, our study elicited that QRXY inhibited the expression of TNFα and inactivated the NLRP3/Caspase-1/IL-1ß pathway, thereby alleviating intestinal mucosal injury and relieving UC in mice.

Assessing the post-treatment therapeutic effect of tongxie in irritable bowel syndrome: A randomized controlled trial.

Diarrhea predominant irritable bowel syndrome (IBS) is a highly relapsing gastrointestinal disorder decreasing the quality of life. Existing studies indicated that the therapeutic effects maintained for a period of time after the treatments were discontinued (post-treatment therapeutic effects or PTTE). In this study, we aim to assess the PTTE of tongxie. We performed a multiple center, controlled, double blind study of patients with IBS randomized to tongxie (n = 120) or placebo (n = 120) for 4 weeks and followed up for 57 weeks. The primary outcomes were abdominal pains and stool consistency. The secondary outcomes were pain frequency and stool frequency. Tertiary outcomes were adverse effects and global overall symptom. The outcome data were collected at days 1, 2, 3, weeks 1 and 4 during the treatment and at days 1, 2, 3, until week 57 during the post-treatment. Significantly more patients receiving tongxie were clinical responders to the primary and secondary endpoints from day 1 until the end of the treatment. The positive effects of tongxie were maintained until 17-25 weeks after tongxie was discontinued. The relapse-free probabilities in the tongxie group were significantly higher than those in the placebo group (P < .001). Twenty-five weeks after the therapies were discontinued could be considered as IBS natural history. During this period, an average of 53.8-56.3% of patients (pool tongxie and placebo data together) had IBS symptoms (pain scale ≥ 3, stool consistency ≥ 5). In particular, at the end of this study (week 61), 145 (54.2%) patients had IBS symptoms. Our results provide clinical insights into efficient and cost-effective management of refractory IBS, and lend support to the IBS management that the selection of a therapy should consider both its effectiveness during treatment and its PTTE after the treatment.

Identification of the Active Constituents and Significant Pathways of Shen-qi-Yi-zhu Decoction on Antigastric Cancer: A Network Pharmacology Research and Experimental Validation.

Shen-qi-Yi-zhu decoction (SQYZD) is an empirical prescription with antigastric cancer (GC) property created by Xu Jing-fan, a National Chinese Medical Master. However, its underlying mechanisms are still unclear. Based on network pharmacology and experimental verification, this study puts forward a systematic method to clarify the anti-GC mechanism of SQYZD. The active ingredients of SQYZD and their potential targets were acquired from the TCMSP database. The target genes related to GC gathered from GeneCards, DisGeNET, OMIM, TTD, and DrugBank databases were imported to establish protein-protein interaction (PPI) networks in GeneMANIA. Cytoscape was used to establish the drug-ingredients-targets-disease network. The hub target genes collected from the SQYZD and GC were parsed via GO and KEGG analysis. Our findings from network pharmacology were successfully validated using an in vitro HGC27 cell model experiment. In a word, this study proves that the combination of network pharmacology and in vitro experiments is effective in clarifying the potential molecular mechanism of traditional Chinese medicine (TCM).

Are personalized tongxie formula based on diagnostic analyses more effective in reducing IBS symptoms?-A randomized controlled trial.

OBJECTIVES: To examine the efficacy and safety ofpersonalized tongxie formulas; to decrease type II errors to minimum. METHODS: Patients were randomized (1:1:1) into three groups given tongxie, placebo, or pinaverium 3 times daily for 4 weeks. Patients in the tongxie group were treated with personalized formulas based on TCM differential diagnosis, i.e., basic type of IBS, IBS due to liver depression and qi stagnation, excess heat in the liver, deficient spleen function, deficient kidney function, and others (groups 1-6). Primary endpoints were significantly greater reductions in abdominal pain and Bristol stool score. Secondary endpoints were reductions in pain and stool frequencies and abdominal discomfort and its frequency. RESULTS: There were significantly more patients whose stool consistencies were improved than pains were relieved in the entire population (p < 0.001), but there was no significantly difference in subpopulation group 3 (p > 0.05). There were significantly more patients whose stool frequencies were reduced than pain frequencies were reduced in the entire population (p < 0.001), but there were no significantly difference in the subpopulation Groups 1, 3, 4, and 6 (p > 0.05). Multiple active ingredients and their mechanisms of actions to relieve IBS symptoms were identified. CONCLUSION: The outcomes in subpopulations may be different from those of the entire population, indicating that personalized formulas are important to achieve optimal outcomes; the active ingredients and innovative mechanisms identified in this study can be the candidates for developing new IBS drugs, and used to manage IBS, respectively. TRIAL REGISTRATION: NCT01641224 (www.ClinicalTrials.gov).

[Medication regularity and potential targets of Professor XU Jing-fan's prescription for treating ulcerative colitis].

Ulcerative colitis (UC) is a chronic nonspecific inflammation mainly involving rectum and colon mucosa, which seriously affects the health and quality of life of patients, and is listed as one of modern refractory diseases by WHO. Professor XU Jing-fan, a great master of traditional Chinese medicine, has accumulated rich experiences in the treatment of UC. The study collected Professor XU's 77 prescriptions of treating UC, analyzed the frequency of traditional Chinese medicines and there categories, and investigated the medication regularity by the system clustering method. The findings showed that the most frequently used drugs were clearing-heat herbs, which were followed by hemostatic herbs, excreting-dampness herbs, improving-digestion herbs and tonifying-Qi herbs. At the same time, the commonly combined drugs were excavated. Finally, in order to analyze potential molecular targets of the frequently used herbs, GO enrichment analysis and KEGG signal pathway enrichment analysis were performed with bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine (BATMAN-TCM). The results indicated that Chinese herbal compounds may treat UC by activating PPAR-γ pathway and regulating intestinal inflammation. The exact mechanisms shall be verified through subsequent molecular biological experiments.

Tongxie Formula Reduces Symptoms of Irritable Bowel Syndrome.

BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is the most common chronic gastrointestinal disorder, yet few drugs are effective in reducing symptoms. Approximately 50% of patients with IBS attempt herbal therapy at least once. We performed a randomized controlled trial to compare the efficacy of the herb formulation tongxie vs placebo or pinaverium (an antispasmodic agent) in reducing symptoms of IBS. METHODS: We performed a trial of 1044 adult patients with IBS (based on Rome III criteria) at 5 hospitals in China, from August 2012 through January 2015. Subjects were randomly assigned (1:1:1) to groups given tongxie (a combination of A macrocephalae, P lactiflora, C reticulata, S divaricata, C pilosula, C wenyujin, C medica, and P cocos, along with other herbs, based on patient features), placebo, or pinaverium (50 mg tablets) 3 times daily for 4 weeks. Primary end points were significantly greater reductions in abdominal pain and Bristol stool score (before vs after the 4-week study period) in patients given tongxie compared with patients given placebo or pinaverium. Secondary end points were reductions in pain and stool frequencies and abdominal discomfort and its frequency. RESULTS: Subjects given tongxie had significant reductions, before vs after the study period, in all 6 symptoms assessed, compared to patients given placebo (P < .001). A significantly higher proportion of patients given tongxie had increased stool consistency (75.6%) than patients given pinaverium (50.6%), and a significantly higher proportion of patients given tongxie had fewer daily stools (72.7%) than subjects given pinaverium (58.3%) (P < .001 for both). However, significantly higher proportions of patients given pinaverium had reduced pain (63.5%) and pain frequency (69.5%) than patients given tongxie (51.4% and 58.6%, respectively; P < .005 for both). CONCLUSIONS: In a randomized controlled trial of patients with IBS in China, we found 4 weeks of tongxie to produce significantly greater reduction in symptoms than placebo, and greater increases in stool consistency and reductions in stool frequency, than patients given pinaverium. Tongxie can therefore be considered an effective alternative therapy for patients with IBS who do not respond well to conventional therapies. Clinicaltrials.gov no: NCT01641224.