Five-Flavor Sophora flavescens Enteric-Coated Capsules for Ulcerative Colitis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Background. Ulcerative colitis (UC), a chronic inflammatory bowel disease, is characterized by abdominal pain, diarrhea, and mucopurulent bloody stool. In recent years, the incidence and prevalence of UC have been increasing consistently. Five-flavor Sophora falvescens enteric-coated capsule (FSEC), a licensed Chinese patent medicine, was specifically used to treat UC. This review was aimed to assess the effectiveness and safety of FSEC for the treatment of UC. Methods. Six electronic databases were searched from inception to March 2021. Randomized clinical trials (RCTs) comparing FSEC or FSEC plus conventional Western medicine with conventional Western medicine in participants with UC were included. Two authors screened all references, assessed the risk of bias, and extracted data independently. Binary data were presented as risk ratios (RRs) with 95% confidence intervals (CIs) and metric data as mean difference (MD) with 95% CI. The overall certainty of the evidence was assessed by GRADE. Results. We included 15 RCTs (1194 participants, 763 in the FSEC group and 431 in the control group). The treatment duration ranged from 42 to 64 days. Twelve trials compared FSEC with conventional Western medicine, and two trials compared FSEC plus conventional medicine with conventional medicine. Another trial compared FSEC plus mesalazine with compound glutamine enteric capsules plus mesalazine. FSEC showed a higher clinical effective rate (improved clinical symptoms, colonoscopy results, and stools) (RR 1.12, 95% CI 1.05 to 1.20; 729 participants; 8 trials; low-quality evidence) as well as the effective rate of traditional Chinese medicine (TCM) syndromes (RR 1.10, 95% CI 1.01 to 1.20; 452 participants; 5 trials; low-quality evidence) compared to mesalazine. There was no significant difference in the adverse events between FSEC and control groups. Conclusions. FSEC may show effectiveness in UC treatment compared to conventional medicine, and the use of FSEC may not increase the risk of adverse events. Due to the limited number of clinical trials and low methodological quality of the included trials, our findings must be interpreted with discretion.

Cholinergic anti-inflammatory pathway ameliorates murine experimental Th2-type colitis by suppressing the migration of plasmacytoid dendritic cells

Ulcerative colitis (UC) is a chronic inflammatory bowel disease. Several studies have demonstrated that α7 nicotinic acetylcholine receptors (α7nAChRs) exert anti-inflammatory effects on immune cells and nicotine suppress UC onset and relapse. Plasmacytoid dendritic cells (pDCs) reportedly accumulate in the colon of UC patients. Therefore, we investigated the pathophysiological roles of α7nAChRs on pDCs in the pathology of UC using oxazolone (OXZ)-induced Th2-type colitis with BALB/c mice. 2-deoxy-D-glucose, a central vagal stimulant suppressed OXZ colitis, and nicotine also ameliorated OXZ colitis with suppressing Th2 cytokines, which was reversed by α7nAChR antagonist methyllycaconitine. Additionally, α7nAChRs were expressed on pDCs, which were located very close to cholinergic nerve fibers in the colon of OXZ mice. Furthermore, nicotine suppressed CCL21-induced bone marrow-derived pDC migration due to Rac 1 inactivation, which was reversed by methyllycaconitine, a JAK2 inhibitor AG490 or caspase-3 inhibitor AZ-10417808. CCL21 was mainly expressed in the isolated lymphoid follicles (ILFs) of the colon during OXZ colitis. The therapeutic effect of cholinergic pathway on OXZ colitis probably through α7nAChRs on pDCs were attributed to the suppression of pDC migration toward the ILFs. Therefore, the activation of α7nAChRs has innovative therapeutic potential for the treatment of UC.

Supplementation With Chinese Medicinal Plant Extracts From Lonicera hypoglauca and Scutellaria baicalensis Mitigates Colonic Inflammation by Regulating Oxidative Stress and Gut Microbiota in a Colitis Mouse Model

Colitis, a chronic inflammatory bowel disease, is characterized by bloody diarrhea and inflammation in the colon. Lonicera hypoglauca (“Shanyinhua” in Chinese) and Scutellaria baicalensis (“Huangqin” in Chinese) are two traditional Chinese medicinal plants rich in polyphenols, such as chlorogenic acid (CGA) and baicalin (BA), with the effects of anti-inflammation and antioxidation. However, it remains unknown whether extracts from L. hypoglauca and S. baicalensis (LSEs) could mitigate colonic inflammation. In the present study, ICR mice (22.23 ± 1.65 g) were allocated to three groups treated with chow diet without (CON) or with dextran sulfate sodium (DSS) (CON+DSS) in water or LSE supplementation in diet with DSS (LSE+DSS), and then inflammatory and oxidative parameters and colonic microbiota were detected. The results showed that LSE (500 mg/kg) treatment mitigated DSS-induced colitis symptoms and restored the shortened colon length, the increased disease activity index (DAI), and the damaged intestinal barrier. In serum, LSE supplementation significantly decreased levels of pro-inflammatory cytokines including interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and lipopolysaccharide (LPS) and increased IL-10 level. Meanwhile, superoxide dismutase (SOD) and catalase (CAT) were increased, and malondialdehyde (MDA) and reactive oxygen species (ROS) levels were decreased. In the colon tissue, qPCR results showed that LSE supplementation dramatically downregulated the transcriptional expression of IL-1β, IL-6, TNF-α, and MDA and upregulated the expression of SOD1, CAT, and IL-10. Additionally, the damaged gut barriers occludin and zonula occludens-1 (ZO-1) in the CON+DSS group were enhanced with LSE supplementation. Furthermore, LSE treatment regulated the gut microbial communities with higher relative abundance of Dubosiella and Ruminococcus torques group and lower relative abundance of Bacteroides and Turicibacter. Moreover, the contents of short-chain fatty acids (SCFAs) as products of gut microbiota were also increased. Correlation analysis showed that the mRNA expression of SOD1 was negatively correlated with TNF-α (r = -0.900, P < 0.05); the mRNA expression of IL-6 (r = -0.779, P < 0.05) and TNF-α (r = -0.703, P < 0.05) had a dramatically negative correlation with Dubosiella. In conclusion, LSE supplementation could effectively ameliorate inflammation by modulating oxidative stress and gut microbiota in a colitis mouse model.

The Communication Between Intestinal Microbiota and Ulcerative Colitis: An Exploration of Pathogenesis, Animal Models, and Potential Therapeutic Strategies

Ulcerative Colitis (UC) is a chronic inflammatory bowel disease. The prolonged course of UC and the lack of effective treatment management make it difficult to cure, affecting the health and life safety of patients. Although UC has received more attention, the etiology and pathogenesis of UC are still unclear. Therefore, it is urgent to establish an updated and comprehensive understanding of UC and explore effective treatment strategies. Notably, sufficient evidence shows that the intestinal microbiota plays an important role in the pathogenesis of UC, and the treating method aimed at improving the balance of the intestinal microbiota exhibits a therapeutic potential for UC. This article reviews the relationship between the genetic, immunological and microbial risk factors with UC. At the same time, the UC animal models related to intestinal microbiota dysbiosis induced by chemical drugs were evaluated. Finally, the potential value of the therapeutic strategies for restoring intestinal microbial homeostasis and treating UC were also investigated. Comprehensively, this study may help to carry out preclinical research, treatment theory and methods, and health management strategy of UC, and provide some theoretical basis for TCM in the treatment of UC.

Erosive acute colitis associated with intestinal spirochetosis

Background Although usually believed to be harmless, intestinal spirochetosis may active erosive colitis associated with intestinal spirochetosis that may mimic idiopathic chronic inflammatory bowel disease. Case presentation. A 49-year-old homosexual male patient sought medical assistance due to asthenia, rectal bleeding, tenesmus, and diarrhea for one month. He had been using corticosteroids for nine months to treat sciatic nerve pain. Colonoscopy showed rectum and distal sigmoid with diffuse erythema with many surface erosions. Rectal biopsy showed inflammatory changes including chronic changes such as architectural distortion and basal plasmacytosis, and active inflammation including crypt microabscesses. In all large bowel sample, dense colonization of intestinal spirochetosis was observed. Patient also had a positive PCR testing for Chlamydia trachomatis. The patient was treated with metronidazole for 14 days, ciprofloxacin for 14 days and azithromycin (single dose). Symptoms improved and the patient is asymptomatic after two months of follow-up. Conclusion In some high-risk groups, intestinal spirochetosis may cause colonic manifestations with overlapping features with intestinal bowel diseases. Awareness of this association is importance since proper antibiotic therapy against Brachyspira (metronidazole) is highly effective. Coinfection with other sexually transmitted infections is common and proper treatment is required.

Care of Women with Chronic Inflammatory Bowel Disease (Chronic IBD) During Pregnancy

The incidence of chronic inflammatory bowel disease (chronic IBD) in persons of reproductive age is high. Chronic IBD does not typically lead to impaired fertility. Nevertheless, the percentage of women suffering from chronic IBD who have children is lower than that of the general population, due to self-imposed childlessness. Providing women with open, unbiased information and, if necessary, helping them to overcome baseless fears should therefore be an essential part of preconception counseling. With the exception of methotrexate, most standard drugs can and should be continued during pregnancy. If the pregnancy occurs during an inactive phase of disease, the rate of complications in pregnancy should, in principle, not be higher than normal. Nevertheless, pregnant women with chronic IBD are classed as high-risk pregnancies. Organ screening in accordance with DEGUM II criteria should be carried out in every case, and women must be monitored for the potential development of placental insufficiency. Any flare-ups which occur during pregnancy should be treated in full. Vaginal delivery can be considered if there is no perianal manifestation of disease; however, the individual risk must be carefully weighed up.

Single center retrospective analysis of association of hidradenitis suppurativa and chronic infl ammatory bowel disease

Summary: Introduction: Association between hidradenitis suppurativa (HS) and chronic inflammatory bowel disease (IBD) exists. Prevalence of IBD in patients with HS is not clear. The aim of this paper is to determine the prevalence of IBD in patients with HS, evaluate risk factors and possible phenotype of patients with HS and IBD. Methods: Single center retrospective analysis of 241 patients with HS was carried out and medical files were searched for inflammatory bowel disease accordingly. Epidemiologic data of HS were collected. Results: IBD had a prevalence of 5.8%. Out of this number 13 (92.9%) suffered from Crohn’s disease (CD) and 1 (7.1%) from ulcerative colitis (UC). Eight patients (57.1%) were referred to the dermatologist by gastroenterologist and in six patients (42.9%) history of IBD was detected by dermatologist during routine examination. Special phenotype of the disease associated with IBD was not confirmed. The study points out possible existence of common comorbidities and risk factors such as smoking and obesity. Discussion: Our study confirmed similar data like those available in literature, where strong association between CD and HS is present and weaker with UC and HS. Conclusion: The prevalence of IBD in HS patients (5.8%) however these patients do not have a distinct HS phenotype. Key words: hidradenitis suppurativa – chronic inflammatory bowel disease – Crohn’s disease – ulcerative colitis – comorbidities – association – risk factors

Changes in the spectrum of protein components and the concentration of phospholipids of the erythrocyte membrane in patients with ulcerative colitis

Ulcerative colitis is a chronic inflammatory bowel disease with unclear etiology. An insufficient amount of data on the etiopathogenetic mechanisms of the disease creates opportunities to research them at the cellular level, including the membrane level. Since the functional state of the cytoplasmic membrane largely depends on protein-lipid interactions, we studied the effect of the proportional ratio of three proteins (glucose transporter, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and glutathione-S-transferase (GST)) on the level of phosphatidylethanolamine and phosphatidylcholine in the erythrocyte membrane of patients with ulcerative colitis during an acute attack. The study involved 51 patients with ulcerative colitis during the acute attack and 26 clinically healthy individuals. The groups are comparable by gender and age to study the proteins of the cytoplasmic membrane, Laemmli electrophoresis technique in polyacrylamide gel was used, followed by an assessment of the intensity of protein bands staining on electropherograms. Phospholipid fractions were obtained using thin-layer chromatography and their content was assessed using the Mathcad 2001 Professional system. Statistical processing was carried out by the program Statistica 10.0 for Windows. Changes of phosphatidylcholine and phosphatidylethanolcholine levels in patients and healthy individuals are not of the same type and are interrelated with changes in the proportion of membrane proteins of the glucose transporter, GAPDH and GST. The proportions of proteins that affect the level of phospholipids have calculated. In patients with ulcerative colitis, a decrease in the level of the studied membrane lipids have revealed in comparison with the clinically healthy group, in addition, an increase in the proportion of the glucose transporter and a decrease in the proportion of GST have noted. In addition, the relationship between an increase in the level of the cytoplasmic membrane phospholipids in ulcerative colitis and a change in the proportion of GAFDH in a smaller direction, which slows down the process of glucose oxidation, was determined. The obtained data confirm the strengthening of the processes of antioxidant protection and the increased need for energy supply of the cell membrane in patients with ulcerative colitis during an acute attack.

Beneficial Effects of Celastrol on Immune Balance by Modulating Gut Microbiota in Dextran Sodium Sulfate-Induced Ulcerative Colitis

Ulcerative colitis (UC) is a chronic inflammatory bowel disease caused by multi-factors including colonic inflammation and microbiota dysbiosis. Previous studies have indicated that Celastrol (CSR) has strong anti-inflammatory and immune-inhibitory effects. Here, we investigated the effects of CSR on colonic inflammation and the mucosal immunity in an experimental colitis model, and addressed the mechanism by which CSR preforms the protective effect. We characterized the therapeutic effects and the potential mechanism of CSR in treating UC using histological staining, intestinal permeability assay, cytokine assay, flow cytometry, fecal microbiota transplantation (FMT), 16S rRNA sequencing, untargeted metabolomics, and cell differentiation approaches. CSR administration significantly ameliorated DSS-induced colitis, as evidenced by the recovery of body weight and colon length, decreased disease activity index (DAI) score, as well as decreased intestinal permeability. CSR down-regulated the secretion of proinflammatory cytokines, upregulated the anti-inflammatory mediators, and improved the balances of Treg/Th1 and Treg/Th17 to maintain colonic immune homeostasis. However, the protective effects of CSR disappeared when the antibiotic cocktail was applied to deplete the gut microbiota, and the gut microbiota-mediated effect was confirmed by FMT. Furthermore, CSR treatment increased the gut microbiota diversity and composition, and raised the metabolic productions of pyruvate and adenosine, which probably involve in gut microbiota mediated protective effect. In conclusion, CSR ameliorates colonic inflammation in a gut microbiota-dependent manner. The underlying protective mechanism is associated with the rectified Treg/Th1 and Treg/Th17 balance, and increased pyruvate and adenosine production. The study provided the solid evidence that CSR might be a promising therapeutic drug for UC.

Informativeness of laboratory methods of research of pregnant women with chronic inflammatory bowel disease

Annotation. The aim of the work is to demonstrate the importance of laboratory parameters in pregnant with chronic inflammatory bowel disease. The examined patients were divided into the main group (ulcerative colitis, n=40) and the control group (practically healthy women, n=30). The formation of observation groups was carried out by methods of continuous and selective analysis. The indicators of vasculo-endothelial growth factor (VEGF), serum levels of vitamin D, homocysteine, markers of neutrophilic intestinal inflammation (serum levels of tumor necrosis factor α and interleukin-4 were studied). Database formation and all calculations were performed using the software packages STATISTICA6.1 (№АХХR910F374605FA) and MedCalc (version 17.7.7, MedCalcSoftware). Statistical processing of quantitative data included the calculation of the mean and standard error of the mean (± m) using parametric criteria (in the case of a normal distribution law) or a nonparametric Mann-Whitney test (if the distribution law differs from the normal one). In the analysis of the informativeness of laboratory methods, it was found that women with chronic inflammatory bowel disease were characterized by: increased levels of fecal calprotectin, proinflammatory cytokines TNFα and interleukin-4, homocysteine. The analysis of markers of endothelial dysfunction in pregnant women with COPD was diagnosed with a significant increase in serum levels of vasculo-endothelial growth factor and an increase in microalbuminuria, which allowed to talk about the association of ulcerative colitis with the development of gestational endotheliopathy in such women.