scholarly journals Exploring the biomarkers and therapeutic mechanism of kidney-yang deficiency syndrome treated by You-gui pill using systems pharmacology and serum metabonomics

RSC Advances ◽  
2018 ◽  
Vol 8 (2) ◽  
pp. 1098-1115 ◽  
Author(s):  
Ruiqun Chen ◽  
Jia Wang ◽  
Chengbin Liao ◽  
Lei Zhang ◽  
Qian Guo ◽  
...  

In this study, systems pharmacology was used to predict the molecular targets of You-gui pills (YGP) and explore the therapeutic mechanism of Kidney-Yang Deficiency Syndrome (KYDS) treated with YGP.

2019 ◽  
Vol 20 (15) ◽  
pp. 3655 ◽  
Author(s):  
Ruiqun Chen ◽  
Jia Wang ◽  
Runhua Zhan ◽  
Lei Zhang ◽  
Xiufeng Wang

Kidney-yang deficiency syndrome (KYDS) is a metabolic disease caused by a neuro-endocrine disorder. The You-gui pill (YGP) is a classic traditional Chinese medicine (TCM) formula for the treatment of KYDS and has been widely used to warm and recuperate KYDS clinically for hundreds of years in China. However, it is unknown whetherthe corresponding targets and metabolic pathways can also be found via using metabonomics based on one platform (e.g., 1H NMR) to study different biological samples of KYDS. At the same time, relevant reports on further molecular verification (e.g., RT-qPCR analysis) of these targets associated with biomarkers and metabolic pathways have not yet, to our knowledge, been seen in KYDS’s research. In the present study, a comprehensive strategy integrating systems pharmacology and 1H NMR-based urinary metabonomics analysis was proposed to identify the target proteins and metabolic pathways that YGP acts on KYDS. Thereafter, further validation of target proteins in kidney tissue was performed through quantitative real-time PCR analysis (RT-qPCR). Furthermore, biochemical parameters and histopathological analysis were studied. As a result, seven target proteins (L-serine dehydratase; phosphoenolpyruvate carboxykinase; spermidine synthase; tyrosyl-tRNA synthetase, glutamine synthetase; 3-hydroxyacyl-CoA dehydrogenase; glycine amidinotransferase) in YGP were discovered to play a therapeutic role in KYDS via affecting eight metabolic pathways (glycine, serine and threonine metabolism; butanoate metabolism; TCA cycle, etc.). Importantly, three target proteins (i.e., 3-hydroxyacyl-CoA dehydrogenase; glutamine synthetase; and glycine amidinotransferase) and two metabolic pathways (butanoate metabolism and dicarboxylate metabolism) related to KYDS, to our knowledge, had been newly discovered in our study. The mechanism of action mainly involved energy metabolism, oxidative stress, ammonia metabolism, amino acid metabolism, and fatty acid metabolism. In short, our study demonstrated that targets and metabolic pathways for the treatment of KYDS by YGP can be effectively found via combining with systems pharmacology and urinary metabonomics. In addition to this, common and specific targets and metabolic pathways of KYDS treated by YGP can be found effectively by integration with the analysis of different biological samples (e.g., serum, urine, feces, and tissue). It is; therefore, important that this laid the foundation for deeper mechanism research and drug-targeted therapy of KYDS in future.


RSC Advances ◽  
2018 ◽  
Vol 8 (48) ◽  
pp. 27448-27463 ◽  
Author(s):  
Ruiqun Chen ◽  
Chengbin Liao ◽  
Qian Guo ◽  
Lirong Wu ◽  
Lei Zhang ◽  
...  

In our study, systems pharmacology was used to predict the molecular targets of Astragalus and Leech, and explore the therapeutic mechanism of type 2 diabetic nephropathy (T2DN) treated with Astragalus and Leech.


2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Yijia Zeng ◽  
Tingna Li ◽  
Xiaorui Zhang ◽  
Yuanyuan Ren ◽  
Qinwan Huang ◽  
...  

Objective. Modern research shows that Haima Duobian pill (HDP) can relieve the kidney yang deficiency syndrome (KYDS), but the mechanism is still unclear. The aim of this work was to study the effects of HDP in a rat model of KYDS. Materials and Methods. The network pharmacology methods were used to predict the therapeutic effects of Haima Duobian pill. Adenine was used to establish the rat model of kidney yang deficiency syndrome. The general physical signs of rats were observed after different doses of Haima Duobian pill (HDP) were given. Serum cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), estradiol (E2), and gonadotropin-releasing hormone (GnRH) levels were determined using enzyme-linked immunosorbent assay (ELISA) kits. Then, the histopathologic changes and sperm activity were detected. Results. HDP could improve the general signs of kidney yang deficiency syndrome rats. After the rats were treated with HDP, the expression of cGMP and E2 was significantly inhibited and the expression of cAMP and T was significantly increased. The pathological damage of testis, epididymis, and seminal vesicle was alleviated, and the sperm activity was improved. Conclusion. For adenine-induced kidney yang deficiency syndrome in rats, HDP had a significant therapeutic effect.


2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Li Ping Zhou ◽  
Wei Wei Liu ◽  
Tian E. Zhang ◽  
Wei Hong Li ◽  
Ling Ling Tan ◽  
...  

Objective. To explore the genetic traits of Kidney-yang deficiency syndrome (KDS).Design. Twelve KDS subjects and three spouses from a typical KDS family were recruited. Their genomic DNA samples were genotyped by Affymetrix 100K single-nucleotide polymorphism (SNP) arrays. The linkage disequilibrium (LD) SNPs were generated using GeneChip DNA analysis software (GDAS, Affymetrix). Genes located within 100 bp of the flanks of LD SNPs were mined via GeneView. 29 exons of the doublecortin domain containing 5 (DCDC5), a representative gene within the flank of an LD SNP, were resequenced.Results. Five LD SNPs display midrange linkage with KDS. Two genes with established functions, DCDC5 and Leucyl-tRNA synthetase, were mined in the flanks of LD SNPs. Resequencing of DCDC5 revealed a nonsynonymous variation, in which 3764T/A was replaced by C/G. Accordingly, the Ser1172was substituted by Pro1172. The S1172P substitution effect was evaluated as “possibly damaging” by PolyPhen.Conclusion. We have identified a genomic variation of DCDC5 based on the LD SNPs derived from a KDS family. DCDC5 and other genes surrounding these SNPs display some relationships with key symptoms of KDS.


2016 ◽  
Vol 192 ◽  
pp. 217-224 ◽  
Author(s):  
Rong Rong ◽  
Rong-rong Li ◽  
Yan-bao Hou ◽  
Jing Li ◽  
Jia-xing Ding ◽  
...  

2018 ◽  
Vol 46 (01) ◽  
pp. 137-155 ◽  
Author(s):  
Ang Ying ◽  
Qing-Tao Yu ◽  
Li Guo ◽  
Wen-Song Zhang ◽  
Jin-Feng Liu ◽  
...  

Ginseng has been reported to have diverse pharmacological effects. One of the therapeutic claims for ginseng is to enhance sexual function. Ginsenosides are considered as the major active constituents. A steaming process can alter the ginsenoside profile of ginseng products. The structure–function relationship of ginsenosides in the treatment of erectile dysfunction (ED) has not been investigated yet. In this work, 15 different processed ginsengs are produced by steaming, and 13 major ginsensosides are quantified by liquid chromatography with UV detection, including Rg1, Re, Rf, Rb1, Rc, Rb2, Rf, Rk3, Rh4, 20S-Rg3, 20R-Rg3, Rk1, and Rg5. Their anti-ED activities are screened using hydrocortisone-induced mice model (Kidney Yang Deficiency Syndrome in Chinese Medicine) and primary corpus cavernosum smooth muscle cells (CCSMCs). A processed ginseng with steaming treatment at 120[Formula: see text]C for 4[Formula: see text]h and five times possesses abundant ginsenosides Rk1, Rk3, Rh4 and Rg5 transformed via deglycosylation and dehydroxylation, and produces optimal activity against ED. The number of sugar molecules, structure of hydroxyl groups and stereoselectivity in ginsenosides affect their anti-ED activity. Among the 13 ginsenosides, Rk1, Rk3, Rh4 and Rg5 are the most efficient in decreasing intracellular calcium levels by inhibiting phosphodiesterase 5A (PDE5A) to reduce the degradation of cyclic guanosine monophosphate (cGMP) in CCSMCs. Rg5 also restrain hypoxia inducible factor-1[Formula: see text] (HIF-1[Formula: see text] expression in hypoxia state, and increase endothelial nitric oxide synthase (eNOS) expression in isolated rat cavernous tissue. These observations suggest a role for steamed ginseng containing two pairs of geometric isomers (i.e., Rk1/Rg5 and Rk3/Rh4) in the treatment of ED.


2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Yang Gong ◽  
Lixing Liu ◽  
Xiaojuan He ◽  
Hongyan Zhao ◽  
Jing Yang ◽  
...  

Objective. To investigate the Th17/Treg immune balance in the ulcerative colitis (UC) patients with two Chinese syndrome: dampness-heat in large intestine (DHLI) and spleen and kidney Yang deficiency (SKYD).Methods. Ninety UC patients (45 were diagnosed with DHLI and 45 with SKYD syndrome) and 23 healthy people were recruited. The serumIL-17 and TGF-β1 levels of these participants were measured with ELISA; the expression of IL-17 and TGF-β1 in colonic mucosa tissue was determined with immunohistochemistry and the percentage of Th17 and Treg in peripheral blood with flow cytometry.Results. The levels of IL-17 and Th17 were significantly higher in both DHLI and SKYD groups than in healthy control group and higher in DHLI than in SKYD group (P<0.05). The levels of TGF-β1 and Treg were significantly lower in the two UC patients groups than in healthy control group; and lower in SKYD group than in DHLI group (P<0.05).Conclusions. UC with DHLI syndrome could be characterized by the elevation of Th17 and IL-17 levels, which indicated an accentuation of inflammatory reaction; UC with SKYD syndrome could be characterized by the reduction of serum Treg and TGF-β1 levels, which represented a depression of immune tolerance.


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