scholarly journals Bu-Shen-Huo-Xue Decoction Ameliorates Diabetic Nephropathy by Inhibiting Rac1/PAK1/p38MAPK Signaling Pathway in High-Fat Diet/Streptozotocin-Induced Diabetic Mice

2020 ◽  
Vol 11 ◽  
Author(s):  
Weisong Wang ◽  
Hongping Long ◽  
Wei Huang ◽  
Ting Zhang ◽  
Lihua Xie ◽  
...  
Keyword(s):  
Renal Function ◽  
Diabetic Nephropathy ◽  
Signaling Pathway ◽  
High Fat Diet ◽  
Epithelial Mesenchymal Transition ◽  
Diabetic Mice ◽  
High Fat ◽  
Active Compounds ◽  
Mesenchymal Transition ◽  
P38mapk Signaling

Diabetic nephropathy (DN), a leading cause of end-stage renal disease, is associated with high morbidity and mortality rates worldwide and the development of new drugs to treat DN is urgently required. Bu-Shen-Huo-Xue (BSHX) decoction is a traditional Chinese herbal formula, made according to traditional Chinese medicine (TCM) theory, and has been used clinically to treat DN. In the present study, we established a high-fat diet/streptozotocin-induced diabetic mouse model and treated the mice with BSHX decoction to verify its therapeutic effects in vivo. Ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was applied to analyze the chemical composition and active compounds of BSHX decoction. Markers of podocyte epithelial-mesenchymal transition and the Rac1/PAK1/p38MAPK signaling pathway were evaluated to investigate the mechanism underlying function of BSHX decoction. BSHX decoction effectively alleviated diabetic symptoms, according to analysis of the renal function indicators, serum creatinine, blood urea nitrogen, serum uric acid, and urinary albumin excretion rate, as well as renal histopathology and ultrastructural pathology of DN mice. We identified 67 compounds, including 20 likely active compounds, in BSHX decoction. The podocyte markers, nephrin and podocin, were down-regulated, while the mesenchymal markers, α-SMA and FSP-1, were up-regulated in DN mouse kidney; however, the changes in these markers were reversed on treatment with BSHX decoction. GTP-Rac1 was markedly overexpressed in DN mice and its levels were significantly decreased in response to BSHX decoction. Similarly, levels of p-PAK1 and p-p38MAPK which indicate Rac1 activation, were reduced on treatment with BSHX decoction. Together, our data demonstrated that BSHX decoction ameliorated renal function and podocyte epithelial-mesenchymal transition via inhibiting Rac1/PAK1/p38MAPK signaling pathway in high-fat diet/streptozotocin-induced diabetic mice. Further, we generated a quality control standard and numerous potential active compounds from BSHX decoction for DN.

scholarly journals Effects of high-fat diet on the epithelial-mesenchymal transition of respiratory tract through the glyoxylic acid cycle of pulmonary microbes and the intervention of saturated hydrogen

2020 ◽  
Author(s):  
Xiangjie Qiu ◽  
Ousman Bajinka ◽  
Lili Wang ◽  
Guojun Wu ◽  
Yurong Tan
Keyword(s):  
Respiratory Tract ◽  
High Fat Diet ◽  
Epithelial Mesenchymal Transition ◽  
Isocitrate Lyase ◽  
Glyoxylate Cycle ◽  
Glyoxylic Acid ◽  
Diet Group ◽  
Control Group ◽  
High Fat ◽  
Mesenchymal Transition

Abstract Background High fat diet is extensively studied to be associated with trending metabolic diseases. In addition to type 2 diabetes and hypertension, high fat diet is strongly associated with asthma and other respiratory diseases among children however, the pathogenicity regarding these pulmonary diseases begs for extensive research. This study investigated the mechanism of the epithelial-mesenchymal transition of respiratory tract, induced by changes in lung microecology with the intake of high-fat diet. 80 five-week-old C57BL6/J male mice were randomly divided into normal control group, normal hydrogen group, high-fat group and high-fat hydrogen group, making 20 mice in each group. The weight of the mice were measured on weekly basis. 6 mice from each group were executed at every second week. Blood sample was collected for lipid testing, lung tissues were collected for 16SrRNA gene sequencing, HE staining, immunofluorescence and quantitative real-time PCR (qPCR).Results Compared with the normal diet group, mice on the high-fat diet group showed increased inflammatory cell infiltration, decreased expression of e-cadherin (E-cad) and increased expression of Twist. There were significant differences in the composition of bacteria in the lung, and the expression of isocitrate lyase (ICL) gene in Pseudomonas aeruginosa , Staphylococcus aureus and Acinetobacter baumannii , which were significantly associated with asthma were seen with a significant increasing trend. After the treatment of saturated hydrogen, the changes in lung microbial population, lung tissue infiltration of inflammatory cells and the transformation of epithelial stroma caused by high-fat diet were moderately alleviated.Conclusion High fat diet can affect the process of airway epithelial stroma by altering the glyoxylate cycle of pulmonary microbes while the pathological process are alleviated by saturated hydrogen by acting on glyoxylate cycle.

Punicalagin alleviates renal injury via the gut-kidney axis in high-fat diet-induced diabetic mice

2022 ◽  
Author(s):  
Qinglian Hua ◽  
Ya Ling Han ◽  
Haifeng Zhao ◽  
Haowen Zhang ◽  
Bei Yan ◽  
...  
Keyword(s):  
Renal Function ◽  
Gut Microbiota ◽  
Renal Injury ◽  
High Fat Diet ◽  
Intestinal Barrier ◽  
Diabetic Mice ◽  
High Fat ◽  
Microbial Ecosystem

Diabetic renal injury was associated with dysbiosis of the gut microbiota and intestinal barrier. Punicalagin (PU) from pomegranates potentially impacts the microbial ecosystem, intestinal barrier, and renal function. Therefore, we...

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