Therapeutic efficacy of the Qing Dai in patients with intractable ulcerative colitis

Introduction: Indigo naturalis (IN) is a blue pigment extracted from Assam indigo and other plants and has been confirmed to be highly effective for ulcerative colitis (UC) treatment in several clinical studies. Objective: We conducted a multicenter double-blind study to confirm the efficacy and safety of short-term IN administration. Methods: A multicenter, randomized controlled trial was conducted between December 2015 and October 2018 in our facilities. Forty-six patients with mild to moderate active UC (Lichtiger index: 5–10) were randomly assigned to the IN group or the placebo group and received 5 capsules (500 mg) twice a day for 2 weeks. We investigated the efficacy according to blood tests and the Lichtiger index before and after administration, and we also examined adverse events. Results: The analysis included 42 patients (20 males, 22 females) with an average age of 45 years. Nineteen patients were assigned to the placebo group, and 23 were assigned to the IN group. After treatment administration, in the placebo group, no change in the Lichtiger index was observed (7.47 to 6.95, p = 0.359), and hemoglobin was significantly reduced (12.7 to 12.4, p = 0.031), while in the IN group, the Lichtiger index (9.04 to 4.48, p = 0.001) and albumin (4.0 to 4.12, p = 0.022) improved significantly. Mild headaches were observed in 5 patients and 1 patient in the IN and placebo groups, respectively. Conclusions: Short-term administration of IN is highly effective without serious adverse events such as pulmonary hypertension or intussusception and may prevent the occurrence of serious adverse events.

Sarcopenia is a pathological condition affecting the development and progression of NAFLD. Urinary levels of titin-N fragment, a biomarker reflecting muscle damage, were measured in NAFLD subjects, and analyzed in a retrospective manner for possible correlations with NAFLD pathophysiology to assess their clinical relevance. This study enrolled 153 NAFLD subjects and 100 subjects without NAFLD, obesity or diabetes mellitus (non-NAFLD). NAFLD subjects had more decreased knee extension strength. NAFLD subjects had greater subcutaneous fat thickness and echo intensity (brightness) of the rectus femoris muscle on ultrasound images; higher levels of the intra- and extra-myocellular lipids (IMCL, EMCL) using ¹H-MRS. Urinary titin-N fragment levels were increased with increasing age but not different between males and females. NAFLD subjects had higher titin-N fragment levels than non-NAFLD subjects. The levels were negatively correlated with skeletal muscle mass and knee extension strength and positively correlated with muscle echo intensity, EMCL, and liver fibrosis scores (NAFLD fibrosis score, FIB-4 index). Multivariate analysis revealed that factors affecting the levels were skeletal mass index, leg skeletal muscle mass, liver stiffness, and NAFLD fibrosis score. Urinary levels of titin-N fragment reflected skeletal muscle deterioration and functional decline, and was closely associated with hepatic pathological conditions in NAFLD subjects.

Exercise can be hypothesized to play an important role in non-alcoholic fatty liver disease (NAFLD) treatment by changing the oral bacterial flora and in the mechanism underlying periodontal disease. We performed salivary component analysis before and after an exercise regimen, and genome analysis of the oral bacterial flora to elucidate the underlying mechanism. Obese middle-aged men with NAFLD and periodontal disease were allocated to 12-week exercise (n = 49) or dietary restriction (n = 21) groups. We collected saliva to compare the oral microflora; performed predictive analysis of metagenomic functions; and, measured the salivary immunoglobulin A, cytokine, bacterial lipopolysaccharide (LPS), and lactoferrin concentrations. The exercise group showed improvements in the clinical indices of oral environment. Salivary component analysis revealed significant reductions in LPS, and lactoferrin during the exercise regimen. Diversity analysis of oral bacterial flora revealed higher alpha- and beta-diversity after the exercise regimen. Analysis of the microbial composition revealed that the numbers of Campylobacter (+83.9%), Corynebacterium (+142.3%), Actinomyces (+75.9%), and Lautropia (+172.9%) were significantly higher, and that of Prevotella (−28.3%) was significantly lower. The findings suggest that an exercise regimen improves the oral environment of NAFLD patients by increasing the diversity of the oral microflora and reducing the number of periodontal bacteria that produce LPS and its capability.