Gut microbiota-derived 5-hydroxyindoleacetic acid from pumpkin polysaccharides supplementation alleviates colitis via MAPKs-PPARγ/NF-κB inhibition.

Polysaccharides from Pumpkin (Cucurbita moschata Duchesne) (PPs) have many pharmacological activities, including anti-oxidant, immune, and intestinal microbiota regulation. These activities have provided some reminders of its potential therapeutic effect on ulcerative colitis (UC), but this has not yet been confirmed. This study preliminarily confirmed its significant anti-UC activity superior to Salicylazosulfapyridine. The average molecular weight of PPs was 3.10 × 105 Da, and PPs mainly comprised Mannose, Rhamnose, Galacturonic acid, Galactosamine, Glucose, and Xylose with molar ratios of 1.58:3.51:34.54:1.00:3.25:3.02. PPs (50, 100 mg/kg) could significantly resist dextran sodium sulfate induced UC on C57BL/6 mice by improving gut microbiota dysbiosis, such as the changes of relative abundance of Bacteroides, Culturomica, Mucispirillum, Escherichia-Shigella, Alistipes and Helicobacter. PPs also reverse the abnormal inflammatory reaction, including abnormal level changes of TNF-α, IFN-γ, IL-1ß, IL-4, IL-6, IL-10, and IL-18. Metabolomic profiling showed that PPs supplementation resulted in the participation of PPAR and MAPK pathways, as well as the increase of 5-hydroxyindole acetic acid (5-HIAA) level. 5-HIAA also exhibited individual and synergistic anti-UC activities in vivo. Furthermore, combination of PPs and 5-HIAA could also elevate the levels of PPARγ in nuclear and inhibit MAPK/NF-ĸB pathway in the colon. This study revealed that PPs and endogenous metabolite 5-HIAA might be developed to treat UC.

Sanguinarine ameliorates DSS induced ulcerative colitis by inhibiting NLRP3 inflammasome activation and modulating intestinal microbiota in C57BL/6 mice.

BACKGROUND: Sanguinarine (SAN) is an important natural anti-inflammatory constitutes and dietary supplementation with SAN could improve the relative length of the intestine, alter gut microbiota, and enhance growth performance of pigs, broiler chickens, and cattle. However, it is unclear whether it has the therapeutic effect on ulcerative colitis (UC). PURPOSE: This study aimed to investigate the therapeutic effect of SAN on UC and explore its mechanisms of action. STUDY DESIGN AND METHODS: Several efficacy indexes of SAN on dextran sulfate sodium (DSS)-induced C57BL/6 mice were evaluated. ELISA kit and western blot analysis were used to evaluate it's anti-inflammatory effect and the mechanism of action. 16S rDNA sequencing detection was used to determine the impact of SAN on gut microbiota. RESULTS: SAN and Sulfasalazine could significantly improve the colon length, the weight loss, the symptoms and the pathological injury of colon in DSS-induced mice. Meanwhile, SAN could decrease the levels of pro-inflammatory cytokines (TNF-α, IFN-γ, IL-1ß, IL-6, IL-13 and IL-18) and increase the levels of anti-inflammatory cytokines (IL-4 and IL-10) in colon, and suppress DSS-induced high expressions of NLRP3, caspase-1 and IL-1ß. In addition, SAN (0.5, 1 µM) could inhibit the expression level of NLRP3 and the activation of caspase-1 and IL-1ß in lipopolysaccharide-stimulated THP-1 cells in non-cytotoxic doses, which was similar to that of MCC950, a specific inhibitor of NLRP3 inflammasome activation. The abundance changes of many genera such as Muribaculaceae_unclassified, Escherichia-Shigella, Lachnospiraceae_NK4A136_group and Helicobacter were also closely related to the improvement of SAN on intestinal inflammatory response. CONCLUSION: SAN exhibited therapeutic effect on DSS-induced colitis by blocking NLRP3-(Caspase-1)/IL-1ß pathway and improving intestinal microbial dysbiosis. SAN might be developed to treat UC and other disorders associated with microbial dysbiosis.

Clinical Efficacy and Safety of Massage for the Treatment of Restless Leg Syndrome in Hemodialysis Patients: A Meta-Analysis of 5 Randomized Controlled Trials.

Aim: We conducted this meta-analysis to evaluate the clinical efficacy and safety of massage for the treatment of hemodialysis patients with restless leg syndrome (RLS). Methods: A comprehensive literature search was performed using the PubMed database, EMBASE database (via OVID), and the Cochrane Library in order to identify eligible randomized controlled trials (RCTs) published before August 31, 2021. After extracted essential data and assessed risk of bias of each eligible study, we calculated the pooled estimate of RLS score and safety after treatment. Statistical analysis was performed by using Review Manager 5.3. Results: Five studies involving 369 hemodialysis patients with RLS were analyzed. The RLS score after treatment [mean difference (MD), -12.01; 95% confidence interval (CI), -14.91 to -9.11] and mean difference of RLS score at the beginning and end of treatment [mean difference (MD), -11.94; 95% confidence interval (CI), -15.45 to -8.43] in a massage group was significantly better than that in route care group. Subgroup analysis suggested that massage with lavender oil also significantly reduced the RLS score after treatment (MD, -14.22; 95% CI, -17.81 to -10.63) and mean difference of RLS score at the beginning and end of treatment (MD, -14.87; 95% CI, -18.29 to -11.45) compared with route care. Meanwhile, massage regime significantly relieved RLS severity compared with route care but did not increase adverse events. Conclusion: Massage may be a preferred treatment modality for hemodialysis patients with RLS because it effectively reduces RLS symptoms, relieves RLS severity, and does not increase the risk of adverse events. However, future study with a larger sample size is warranted due to the fact that only limited number of eligible studies with small sample size are enrolled.

[Clinical observation on treatment of chronic allograft nephropathy with colquhounia root tablet combined with immunosuppressive protocol].

OBJECTIVE: To observe the effects of Colquhounia root tablet (CRT) combined with immunosuppressive protocal in treating patients with chronic allograft nephropathy (CAN). METHODS: Thirty-three patients of CAN, with urinary protein > or = 1.0 g/24 h and serum creatinine (SCr) > or =150 (micromol/L), were assigned to two groups, the 15 in the treated group treated with CRT combining modified immunosuppressive protocol (IIP) therapy and the 18 in the control group treated with IIP alone, all for 6 months. The clinical efficiency, 24 h urinary protein and clearance of creatinine (CCr) were observed. RESULTS: The effective rate in the treated group [60% (9/15 cases)] was significantly higher than that in the control group [22.0% (4/18 cases), P < 0.05], and the lowering of 24 h urinary protein in the former was more significant than in the latter at the end of the 3rd and the 6th month of treatment (P < 0.05). At the end of 12-month follow-up, SCr and CCr level were stable in the treated group, while in the control group, SCr level increased and CCr level decreased significantly (P < 0.05), comparisons of the two indexes between the two groups at the end of the therapeutic course and follow-up study all showed significant differences (P < 0.05). Serum creatinine doubling to baseline were seen in 2 patients of the treated group and 7 of the control group. One patient in the treated group and 4 in the control group entered the end stage of renal disease. CONCLUSION: Therapy with CRT combined IIP seems to be more effective in reducing urinary protein excretion in patients with CAN than that with IIP alone, and a more favorable renal function preserving effect of the former is shown by a short-term follow-up.

[Clinical study on treatment of early diabetic nephropathy by tangshenling combined with telmisartan].

OBJECTIVE: To study the effects and the possible mechanism of Tangshenling (TSL) combined with telmisartan on early diabetic nephropathy (DN). Methods Eighty-one patients with early DN were randomly assigned into the control group (n=40) treated by telmisartan alone and the treated group (n=41) treated by TSL combined with telmisartan, and the conventional western therapy was given to all patients in both groups. Changes before and after treatment in symptoms and levels of urine albumin excretion rate (UAER), urine transforming growth factor beta1 (TGF-beta1), retinol binding protein (RBP) and beta2-microglobulin (beta2-MG), fasting blood glucose (FBG), serum creatinine (SCr), blood lipids, plasma atrial natriuretic peptide (ANP), serum collagen type IV (Col-IV) and TGF-beta1 were observed. RESULTS: Before treatment, no significant difference was shown in all these indexes between the treated group and the control group. After 8 weeks of treatment, the effective rates in symptoms improvement were higher in the treated group than those in the control group (P < 0.05 or P < 0.01); UAER, urine RBP, beta2-MG and TGF-beta1, serum TC, TG, Col-IV and TGF-beta1, and blood pressure were significantly lowered in both groups after treatment (P < 0.05 or P < 0.01); and the treated group showed a better effect than the control group in improving all the above-mentioned indexes except the blood pressure (P < 0.05); but there was no significant difference in the changes of FBG, SCr and blood pressure between the 2 groups (P > 0.05); after treatment, plasma ANP significantly lowered in the treated group (P < 0.01), while there was no significant change of that in the control group (P > 0.05). Conclusion Combination of TSL and telmisartan has a better effect than telmisartan on DN in early stage. Its mechanism might be related to the decrease of ANP and TGF-beta1 and improvement of lipids metabolism and renal tubular interstitial pathological changes.

[Clinical observation on treatment of chronic allograft nephropathy with bailing capsule].

OBJECTIVE: To observe the effects of Bailing Capsule (BLC, a dry powder-formed preparation of Cordyceps sinensis mycelia) on chronic allograft nephropathy (CAN). METHODS: A comparative synchronous study was conducted between 36 CAN patients treated with BLC 9.0 g/d (treated group) for 12 weeks and 15 CAN patients treated without BLC (control group). The changes of renal function, endogenous creatinine clearance rate, volume of urinary protein and urinary protein components, including immune globulin (Ig) and albumin (Alb), urinary retinol binding protein (RBP) and beta2-microglobulin (beta2-MG), as well as the incidence rate of leucopenia before and after treatment in the two groups were compared. RESULTS: Compared with the control group, BLC showed more significant effects in lowering urinary protein (0.89 +/- 0.53 g/d in the treated group vs 1.31 +/- 0.59 g/d in the control group after treatment, the same below), serum creatinine (206.48 +/- 30.61 micromol/L vs 240.17 +/- 29.55 micromol/L), relieving glomerular and tubular proteinuria represented by levels of Ig, Al, RBP and beta2-MG in urine, increasing endogenous creatine clearance rate (37.33 +/- 9.91 ml/min vs. 31.92 +/- 10.95 ml/min), and reducing the incidence rate of leucopenia (2.8% vs 13.3%) in CAN patients. CONCLUSION: BLC has certain therapeutical effect on CAN. It could relieve injury in glomerulus and tubular interstitium and has preventive and therapeutical effect on leucopenia.

[Effects of Tangshenling Mixture and benazepril on rats with diabetic nephropathy and its mechanism].

OBJECTIVE: To investigate the effects of Tangshenling Mixture (TSLM) and benazepril on rats with diabetic nephropathy (DN) and its mechanism. METHODS: Diabetic nephropathy was induced in rats by intraperitoneal injection of streptozotocin. Fifty-eight rats with DN were randomly divided into four groups: untreated group, TSLM-treated group, TSLM plus benazepril-treated group and benazepril-treated group. Another seven normal rats were included in normal control group. Then, rats in each group were accordingly given normal saline, TSLM, TSLM plus benazepril and benazepril orally for six weeks respectively. Blood and urine biochemical indexes, plasma atrial natriuretic factor (ANF), pathomorphology of renal tissue, transforming growth factor beta1 (TGF-beta1) and glucose transporter 1 (GLUT1) mRNAs in renal tissue were observed. RESULTS: Both TSLM and benazepril could decrease urinary albumin excretion rates, creatinine clearance and ratio of kidney weight to body weight of the rats with DN as well as reduce the pathological damages of the renal tissues. TSLM could reduce the level of plasma ANF and the expression of GLUT1 mRNA, but had no significant effect on the expression of TGF-beta1 mRNA. Benazepril could reduce the expression of TGF-beta1 mRNA, but had no significant effect on plasma ANF and the expression of GLUT1 mRNA. CONCLUSION: TSLM can reduce the pathological damages of renal tissues in rats with early-stage DN, and its mechanism may relate to decreasing the level of plasma ANF and the expression of GLUT1 mRNA which is different from that of benazepril. It seems that TSLM has synergetic effect with benazepril.