scholarly journals Tangshen formula modulates gut Microbiota and reduces gut-derived toxins in diabetic nephropathy rats

2020 ◽  
Vol 129 ◽  
pp. 110325 ◽  
Author(s):  
TingTing Zhao ◽  
HaoJun Zhang ◽  
Xingbin Yin ◽  
HaiLing Zhao ◽  
Liang Ma ◽  
...  
2018 ◽  
Vol 9 ◽  
Author(s):  
Peng Liu ◽  
Liang Peng ◽  
Haojun Zhang ◽  
Patrick Ming-Kuen Tang ◽  
Tingting Zhao ◽  
...  

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Haojun Zhang ◽  
Ping Li ◽  
Frank J. Burczynski ◽  
Yuewen Gong ◽  
Patrick Choy ◽  
...  

Diabetic nephropathy is one of the most significant microvascular complications in patients with type 2 diabetics. The concise mechanism of diabetic nephropathy is unknown and there is no successful treatment. The objective of study was to investigate effects of Chinese herbs (Tangshen Formula) on diabetic nephropathy in Otsuka Long-Evans Tokushima Fatty (OLETF) rats. OLETF rats and LETO rats were divided into four groups: LETO control, OLETF diabetics, OLETF diabetics treated with Tangshen Formula, and OLETF diabetics treated with Monopril. Body weight, blood glucose, and 24 h urinary proteins were measured once every four weeks. Blood samples and kidney tissues were obtained for analyses of total cholesterol, triglyceride, whole blood viscosity, plasma viscosity, and pathohistological examination at 36 and 56 weeksrespectively. Untreated OLETF rats displayed diabetic nephropathy over the study period. Treatment of OLETF rats with Tangshen Formula attenuated the increases in blood glucose, body weight, 24 h urinary protein content, serum total cholesterol, whole blood viscosity and plasma viscosity at certain time. Treatment with Tangshen Formula also reduced glomerulosclerotic index and interstitial fibrotic index seen in OLETF rats. In conclusion, Tangshen Formula could attenuate the development of diabetic nephropathy in OLETF rat diabetic model.


2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Weie Zhou ◽  
Xuefeng Zhou ◽  
Yuan Zhang ◽  
Yuyang Wang ◽  
Wenjie Wu ◽  
...  

Diabetic nephropathy (DN) is one of the common and severe microvascular complications of diabetes mellitus (DM). The occurrence and development of DN are related to multiple factors in the human body, which makes DN a complex disease, and the pathogeneses of DN have not yet been fully illustrated. Furthermore, DN lacks effective drugs for treatment nowadays. Chinese herbal medicine (CHM) often shows the feature of multicomponents, multitargets, multipathways, and synergistic effects and shows a promising source of new therapeutic drugs for DN. As a CHM, Tangshen Formula (TSF) was used to treat DN patients in China. However, its bioactive compounds and holistic pharmacological mechanisms on DN are both unclear. A network pharmacology approach was firstly applied to explore multiple active compounds and multiple key pharmacological mechanisms for TSF treating DN by drug-targeted interaction databases, herb-compound-target network, protein-protein interaction network, compound-target-pathway network, and analysis methods. And the results showed that TSF have the characteristic of multicomponents, multitargets, multipathways, and synergistic effects for treating DN. The quercetin, naringenin, kaempferol, and isorhamnetin as key active compounds and the PI3K-Akt signaling pathway, TNF signaling pathway, nonalcoholic fatty liver disease (NAFLD), focal adhesion, rap1 signaling pathway, T cell receptor signaling pathway, MAPK signaling pathway, and insulin resistance as the key molecular mechanisms play important roles in TSF treating DN. Moreover, quercetin, naringenin, kaempferol, and isorhamnetin were successfully detected in TSF by the UHPLC-MS/MS analysis method. And their concentrations were 0.224, 8.295, 0.0564, and 0.0879 mg·kg-1, respectively. The present findings not only provide new insights for a deeper understanding of the constituent basis and pharmacology of TSF but also provide guidance for further pharmacological studies on TSF.


Author(s):  
Yue‑Guang Du ◽  
Ke‑Na Zhang ◽  
Zong‑Lei Gao ◽  
Fengjiao Dai ◽  
Xi‑Xi Wu ◽  
...  

Planta Medica ◽  
2014 ◽  
Vol 80 (08/09) ◽  
pp. 614-621 ◽  
Author(s):  
Jingjing Hu ◽  
Xuemei Fan ◽  
Xiansheng Meng ◽  
Yiming Wang ◽  
Qionglin Liang ◽  
...  

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Xue Mei Fan ◽  
Chun Lian Huang ◽  
Yi Ming Wang ◽  
Ning Li ◽  
Qiong Lin Liang ◽  
...  

Objective. Cytokines are essential promoters in the pathogenesis of diabetic nephropathy (DN) in type 2 diabetes. The following study investigates the adjustment mechanism of Tangshen formula (TSF) on cytokine expressions in db/db mice (DN animal model). Materials and Methods. Db/db mice were randomly divided into three groups. The treated groups were orally administered with TSF and losartan for 12 weeks. Biochemical and histological examinations were determined at 8 and 12 weeks posttreatment, while the cytokine antibody array analysis was applied to analyze the expression of 144 cytokines in kidney tissues at the end of the 12th week posttreatment. Results. TSF significantly reduced urinary albumin excretion and the levels of blood glucose, cholesterol, triglyceride, creatinine, and urea nitrogen. Furthermore, a significant decrease in glomerulus and mesangial area, as well as the downregulation of 24 cytokines and upregulated expressions of 5 cytokines, was found in the TSF-treated mice. Conclusions. The present study reveals that TSF could ameliorate the metabolic anomalies and renal injury in db/db mice. One of the important mechanisms for treatment of DN using the treatment of TSF is the control of the JAK/STAT signaling pathway via regulation of IL-2, IL-6, IL-13, Il-15, and IFN-γ expression.


2020 ◽  
Vol 31 (6) ◽  
pp. 1267-1281 ◽  
Author(s):  
Yan Jun Li ◽  
Xiaochen Chen ◽  
Tony K. Kwan ◽  
Yik Wen Loh ◽  
Julian Singer ◽  
...  

BackgroundStudies have reported “dysbiotic” changes to gut microbiota, such as depletion of gut bacteria that produce short-chain fatty acids (SCFAs) through gut fermentation of fiber, in CKD and diabetes. Dietary fiber is associated with decreased inflammation and mortality in CKD, and SCFAs have been proposed to mediate this effect.MethodsTo explore dietary fiber’s effect on development of experimental diabetic nephropathy, we used streptozotocin to induce diabetes in wild-type C57BL/6 and knockout mice lacking the genes encoding G protein–coupled receptors GPR43 or GPR109A. Diabetic mice were randomized to high-fiber, normal chow, or zero-fiber diets, or SCFAs in drinking water. We used proton nuclear magnetic resonance spectroscopy for metabolic profiling and 16S ribosomal RNA sequencing to assess the gut microbiome.ResultsDiabetic mice fed a high-fiber diet were significantly less likely to develop diabetic nephropathy, exhibiting less albuminuria, glomerular hypertrophy, podocyte injury, and interstitial fibrosis compared with diabetic controls fed normal chow or a zero-fiber diet. Fiber beneficially reshaped gut microbial ecology and improved dysbiosis, promoting expansion of SCFA-producing bacteria of the genera Prevotella and Bifidobacterium, which increased fecal and systemic SCFA concentrations. Fiber reduced expression of genes encoding inflammatory cytokines, chemokines, and fibrosis-promoting proteins in diabetic kidneys. SCFA-treated diabetic mice were protected from nephropathy, but not in the absence of GPR43 or GPR109A. In vitro, SCFAs modulated inflammation in renal tubular cells and podocytes under hyperglycemic conditions.ConclusionsDietary fiber protects against diabetic nephropathy through modulation of the gut microbiota, enrichment of SCFA-producing bacteria, and increased SCFA production. GPR43 and GPR109A are critical to SCFA-mediated protection against this condition. Interventions targeting the gut microbiota warrant further investigation as a novel renoprotective therapy in diabetic nephropathy.


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