scholarly journals Antistress Effects of San-Huang-Xie-Xin Decoction on Restraint-Stressed Mice Revealed by 1H NMR-Based Metabolomics and Biochemistry Analysis

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Wei Peng ◽  
Huan Du ◽  
Guangli Liu ◽  
Qing Zhang ◽  
Tingting Kuang ◽  
...  
Keyword(s):  
Normal Group ◽  
H Nmr ◽  
Scutellariae Radix ◽  
Stressed Group ◽  
Candidate Drug ◽  
Centrifuge Tube ◽  
Coptidis Rhizoma ◽  
Underlying Mechanisms ◽  
Endogenous Metabolites ◽  
Necrosis Factor

San-Huang-Xie-Xin decoction (SHXXD), composed of Rhei Radix et Rhizoma, Coptidis Rhizoma, and Scutellariae Radix, is a representative antipyretic and detoxifying prescription in traditional Chinese medicine. In this study, we investigated the antistress effects and underlying mechanisms of San-Huang-Xie-Xin decoction (SHXXD) on restraint-stressed mice by 1H NMR-based metabolomics combined with biochemistry assay. A total of 48 male mice (5 weeks old, 18-22 g) were divided randomly into 6 groups (n=8), including the normal group, restraint-stressed group, vitamin C group (positive drug, 17 mg/kg), and 3-dosage groups of SHXXD (200, 400, and 800 mg/kg). The stress model was induced by restraining mice in a polypropylene centrifuge tube for 6 h every day. The rotarod test was performed, and several biochemical indicators were measured. Moreover, other 24 animals were divided into 3 groups (n=8) including the normal group, restraint-stressed group, and SHXXD group (800 mg/kg) for 1H NMR-based metabolomics analysis. Our results showed that SHXXD significantly increased the rotarod time, thymus index, spleen index, and the levels of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and interleukin- (IL-) 2, but decreased the levels of malondialdehyde (MDA), IL-1β, tumor necrosis factor- (TNF-) α, corticosterone (CORT), and adrenocorticotropic hormone (ACTH) in restraint-stressed mice. Moreover, the contents of eight endogenous metabolites that were changed by restraint stress were significantly reversed by SHXXD. The results of both metabolomics and biochemical analysis indicated that SHXXD (800 mg/kg, p.o.) could improve the biochemical changes and metabolic disorders in restraint-stressed mice by antioxidation and anti-inflammation, enhancing the body’s immune function and restoring several disturbed metabolic pathways (i.e., lipid metabolism, glycolysis and gluconeogenesis, inflammatory injury, and energy metabolism). Taken together, these results indicated that SHXXD has a potential antistress effect in restraint-stressed mice and could be considered as a candidate drug for stress-related disorders.

Inhibitory effects of Coptidis Rhizoma on the intestinal absorption and metabolism of Scutellariae Radix

2021 ◽  
pp. 113785
Author(s):  
Wei Zheng ◽  
Guixia Sun ◽  
Jianhua Chen ◽  
Zhihui Li ◽  
Ting Zhang ◽  
...  
Keyword(s):  
Intestinal Absorption ◽  
Inhibitory Effects ◽  
Scutellariae Radix ◽  
Coptidis Rhizoma

scholarly journals PP2Acα promotes macrophage accumulation and activation to exacerbate tubular cell death and kidney fibrosis through activating Rap1 and TNFα production

2021 ◽  
Author(s):  
Yan Liang ◽  
Xiaoli Sun ◽  
Mingjie Wang ◽  
Qingmiao Lu ◽  
Mengru Gu ◽  
...  
Keyword(s):  
Cell Death ◽  
Tubular Cell ◽  
Kidney Fibrosis ◽  
Tubular Cells ◽  
Ureter Obstruction ◽  
Underlying Mechanisms ◽  
Factor Α ◽  
Rap1 Activation ◽  
Necrosis Factor ◽  
Macrophage Accumulation

AbstractMacrophage accumulation and activation play an essential role in kidney fibrosis; however, the underlying mechanisms remain to be explored. By analyzing the kidney tissues from patients and animal models with kidney fibrosis, we found a large induction of PP2Acα in macrophages. We then generated a mouse model with inducible macrophage ablation of PP2Acα. The knockouts developed less renal fibrosis, macrophage accumulation, or tubular cell death after unilateral ureter obstruction or ischemic reperfusion injury compared to control littermates. In cultured macrophages, PP2Acα deficiency resulted in decreased cell motility by inhibiting Rap1 activity. Moreover, co-culture of PP2Acα−/− macrophages with tubular cells resulted in less tubular cell death attributed to downregulated Stat6-mediated tumor necrosis factor α (TNFα) production in macrophages. Together, this study demonstrates that PP2Acα promotes macrophage accumulation and activation, hence accelerates tubular cell death and kidney fibrosis through regulating Rap1 activation and TNFα production.

scholarly journals Coptidis Rhizoma Extract Reverses 5-Fluorouracil Resistance in hct116 Human Colorectal Cancer Cells via Modulation of Thymidylate Synthase

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 1856
Author(s):  
Yong-Hwi Kang ◽  
Jin-Seok Lee ◽  
Nam-Hun Lee ◽  
Seung-Hyung Kim ◽  
Chang-Seob Seo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Thymidylate Synthase ◽  
Cell Cycle Distribution ◽  
Human Colorectal Cancer ◽  
Common Cancer ◽  
G1 Phase Arrest ◽  
Colorectal Cancer Cells ◽  
Coptidis Rhizoma ◽  
Underlying Mechanisms ◽  
Human Colorectal Cancer Cells

Colorectal cancer (CRC) is a malignancy of the colon or rectum. It is ranked as the third most common cancer in both men and women worldwide. Early resection permitted by early detection is the best treatment, and chemotherapy is another main treatment, particularly for patients with advanced CRC. A well-known thymidylate synthase (TS) inhibitor, 5-fluorouracil (5-FU), is frequently prescribed to CRC patients; however, drug resistance is a critical limitation of its clinical application. Based on the hypothesis that Coptidis Rhizoma extract (CRE) can abolish this 5-FU resistance, we explored the efficacy and underlying mechanisms of CRE in 5-FU-resistant (HCT116/R) and parental HCT116 (HCT116/WT) cells. Compared to treatment with 5-FU alone, combination treatment with CRE and 5-FU drastically reduced the viability of HCT116/R cells. The cell cycle distribution assay showed significant induction of the G0/G1 phase arrest by co-treatment with CRE and 5-FU. In addition, the combination of CRE and 5-FU notably suppressed the activity of TS, which was overexpressed in HCT116/R cells, as compared to HCT116/WT cells. Our findings support the potential of CRE as an adjuvant agent against 5-FU-resistant colorectal cancers and indicate that the underlying mechanisms might involve inhibition of TS expression.

Combined proteomic and metabonomic studies in three genetic forms of the renal Fanconi syndrome

2007 ◽  
Vol 293 (2) ◽  
pp. F456-F467 ◽  
Author(s):  
Annalisa Vilasi ◽  
Pedro R. Cutillas ◽  
Anthony D. Maher ◽  
Severine F. M. Zirah ◽  
Giovambattista Capasso ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Fanconi Syndrome ◽  
Low Molecular Weight ◽  
Renal Fanconi Syndrome ◽  
Dent’S Disease ◽  
H Nmr ◽  
Low Molecular Weight Proteinuria ◽  
Dent's Disease ◽  
Underlying Mechanisms ◽  
Normal Urine

The renal Fanconi syndrome is a defect of proximal tubular function causing aminoaciduria and low-molecular-weight proteinuria. Dent's disease and Lowe syndrome are defined X-linked forms of Fanconi syndrome; there is also an autosomal dominant idiopathic form (ADIF), phenotypically similar to Dent's disease though its gene defect is still unknown. To assess whether their respective gene products are ultimately involved in a common reabsorptive pathway for proteins and low-molecular-mass endogenous metabolites, we compared renal Fanconi urinary proteomes and metabonomes with normal (control) urine using mass spectrometry and1H-NMR spectroscopy, respectively. Urine from patients with low-molecular-weight proteinuria secondary to ifosfamide treatment (tubular proteinuria; TP) was also analyzed for comparison. All four of the disorders studied had characteristic proteomic and metabonomic profiles. Uromodulin was the most abundant protein in normal urine, whereas Fanconi urine was dominated by albumin.1H-NMR spectroscopic data showed differences in the metabolic profiles of Fanconi urine vs. normal urine, due mainly to aminoaciduria. There were differences in the urinary metabolite and protein compositions between the three genetic forms of Fanconi syndrome: cluster analysis grouped the Lowe and Dent's urinary proteomes and metabonomes together, whereas ADIF and TP clustered together separately. Our findings demonstrate a distinctive “polypeptide and metabolite fingerprint” that can characterize the renal Fanconi syndrome; they also suggest that more subtle and cause-specific differences may exist between the different forms of Fanconi syndrome that might provide novel insights into the underlying mechanisms and cellular pathways affected.

scholarly journals Effect of Xueniao Capsule on Escherichia coli-Induced Acute Pyelonephritis Rats by 1H NMR-Based Metabolomic Approach

2019 ◽  
Vol 2019 ◽  
pp. 1-12
Author(s):  
Xuliang Hao ◽  
Pan He ◽  
Yan Ni ◽  
Jing Yao ◽  
Yankun Yang ◽  
...  
Keyword(s):  
Chemical Analysis ◽  
Acute Pyelonephritis ◽  
Bacterial Count ◽  
Action Mechanism ◽  
Chemical Difference ◽  
Future Studies ◽  
H Nmr ◽  
Multiple Components ◽  
Endogenous Metabolites ◽  
Metabolomic Approach

Xueniao capsule, one of the famous traditional Chinese medicine (TCM) formulas, has been proved to be effective for treating acute pyelonephritis (APN) in the clinic. However, the probable mechanisms are still unclear. This study was aimed at investigating the therapeutic effect and action mechanism of Xueniao capsule on acute pyelonephritis rats. Chemical analysis of Xueniao capsule and four different extracts was conducted by HPLC and GC-MS. 21 compounds were identified in the Xueniao capsule, and obvious chemical difference was also revealed among the different extracts by chemical analysis. Metabolomics, combined with bacteriological examination, traditional histopathology, and biochemical parameters, was used to evaluate the effects of Xueniao capsule and four different extracts. After treatment with Xueniao capsule, the bacterial count of urine was decreased and the renal lesions of APN rats were ameliorated by histopathology inspection. Levels of Scr and Ucr, IL-1α, IL-1β, IL-6, IL-10, CXCL-2, and MCP-1 were decreased significantly, and the reserving effect of Xueniao capsule was superior to the different extracts and norfloxacin. 16 endogenous metabolites related to APN model were revealed, and 12 of them could be reversed by the Xueniao capsule. 1H NMR metabolomic results demonstrated that the formula of Xueniao capsule played the best therapeutic role on APN through regulating energy metabolism and alterations of osmotic pressure. The effect of Xueniao capsule on the APN was the synergistic actions of multiple components, which need to be further investigated in future studies.

scholarly journals Shengjing Capsule Improves Spermatogenesis through Upregulating Integrin α6/β1 in the NOA Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Jiamin Wang ◽  
Shankun Zhao ◽  
Lianmin Luo ◽  
Yangzhou Liu ◽  
Ermao Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Sperm Quality ◽  
Sperm Count ◽  
Spermatogonial Stem Cells ◽  
Normal Group ◽  
Seminiferous Tubules ◽  
High Dose ◽  
Sprague Dawley ◽  
Underlying Mechanisms ◽  
Almost All

Objective. To evaluate the therapeutic effect of Shengjing capsules on nonobstructive azoospermia (NOA) in the rat model. Methods. Twenty-five male Sprague–Dawley rats were randomly divided into five groups as follows (n=5 per group): normal group, NOA group, and three Shengjing capsule treatment groups (low-dose, medium-dose, and high-dose groups, respectively). HE staining and semen smear were performed to assess sperm quality. The expression levels of PI3K/AKT and integrin α6/β1 were measured by qRT-PCR and western blot analyses. Results. In the NOA group, almost all of the seminiferous tubules were vacuolated with a thin layer of basal compartment containing some spermatogonial stem cells. The counts of sperms in the NOA group were strongly lower than those of the normal group (P=0.0001). The expression of PI3K/AKT and integrin α6/β1 was scarcely expressed in the NOA group. All indexes mentioned above were significantly different from those of the medium- and high-dose groups (P=0.001, all). The sperm count of rats treated with Shengjing capsules was significantly higher than that of the NOA group (P=0.0001). The rats of Shengjing capsule groups had more layers of spermatogonial stem cells and spermatocytes, and some had intracavitary sperms. Conclusions. Shengjing capsules may be a promising therapeutic medicine for NOA. The underlying mechanisms might involve activating SSCs by upregulating the integrin α6/β1 expression via the PI3K/AKT pathway.

scholarly journals 1H NMR Metabolic Profiling of Biofluids from Rats with Gastric Mucosal Lesion and Electroacupuncture Treatment

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Jingjing Xu ◽  
Kian-Kai Cheng ◽  
Zongbao Yang ◽  
Chao Wang ◽  
Guiping Shen ◽  
...  
Keyword(s):  
Gastrointestinal Disorder ◽  
Mucosal Lesion ◽  
Proton Nuclear Magnetic Resonance ◽  
Gastric Mucosal Lesion ◽  
H Nmr ◽  
Metabolic Network Analysis ◽  
Healthy State ◽  
Stomach Meridian ◽  
And Control ◽  
Endogenous Metabolites

Gastric mucosal lesion (GML) is a common gastrointestinal disorder with multiple pathogenic mechanisms in clinical practice. In traditional Chinese medicine (TCM), electroacupuncture (EA) treatment has been proven as an effective therapy for GML, although the underlying healing mechanism is not yet clear. Here, we used proton nuclear magnetic resonance- (1H NMR-) based metabolomic method to investigate the metabolic perturbation induced by GML and the therapeutic effect of EA treatment on stomach meridian (SM) acupoints. Clear metabolic differences were observed between GML and control groups, and related metabolic pathways were discussed by means of online metabolic network analysis toolbox. By comparing the endogenous metabolites from GML and GML-SM groups, the disturbed pathways were partly recovered towards healthy state via EA treated on SM acupoints. Further comparison of the metabolic variations induced by EA stimulated on SM and the control gallbladder meridian (GM) acupoints showed a quite similar metabolite composition except for increased phenylacetylglycine, 3,4-dihydroxymandelate, and meta-hydroxyphenylacetate and decreased N-methylnicotinamide in urine from rats with EA treated on SM acupoints. The current study showed the potential application of metabolomics in providing further insight into the molecular mechanism of acupuncture.

scholarly journals How to Find Candidate Drug-targets for Antiepileptogenic Therapy?

2020 ◽  
Vol 18 (7) ◽  
pp. 624-635 ◽  
Author(s):  
Nian Yu ◽  
Xing-jian Lin ◽  
Qing Di
Keyword(s):  
Drug Targets ◽  
Neuronal Excitability ◽  
Experimental Models ◽  
Pathological Process ◽  
Spontaneous Seizures ◽  
Candidate Drug ◽  
Underlying Mechanisms ◽  
Drug Resistant Epilepsy ◽  
Brain Insults ◽  
Normal Status

Although over 25 antiepileptic drugs (AEDs) have become currently available for clinical use, the incidence of epilepsy worldwide and the proportions of drug-resistant epilepsy among them are not significantly reduced during the past decades. Traditional screens for AEDs have been mainly focused on their anti-ictogenic roles, and their efficacies primarily depend on suppressing neuronal excitability or enhancing inhibitory neuronal activity, almost without the influence on the epileptogenesis or with inconsistent results from different studies. Epileptogenesis refers to the pathological process of a brain from its normal status to the alterations with the continuous prone of unprovoked spontaneous seizures after brain insults, such as stroke, traumatic brain injury, CNS infectious, and autoimmune disorders, and even some specific inherited conditions. Recently growing experimental and clinical studies have discovered the underlying mechanisms for epileptogenesis, which are multi-aspect and multistep. These findings provide us a number of interesting sites for antiepileptogenic drugs (AEGDs). AEGDs have been evidenced as significantly roles of postponing or completely blocking the development of epilepsy in experimental models. The present review will introduce potential novel candidate drug-targets for AEGDs based on the published studies.

scholarly journals 1H-NMR Metabolomics Analysis of The Intervention Effects of Ruangan Xiaoji Decoction on CCl4 Induced Liver Fibrosis in Rats

2020 ◽  
Author(s):  
Weiliang Zhu ◽  
Guoqing Wu ◽  
Wenrui Zhu ◽  
Tianwen Zhao ◽  
Hong-Jiang Zhang ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Liver Tissue ◽  
Acid Metabolism ◽  
Clinical Chemistry ◽  
Tca Cycle ◽  
Control Group ◽  
Obvious Effect ◽  
Nmr Metabolomics ◽  
H Nmr ◽  
Endogenous Metabolites

Abstract Background: Liver fibrosis is a common consequence of chronic liver diseases resulting from multiple etiologies. Early clinical application shows that Ruangan Xiaoji Decoction (RGXJD) has a very obvious effect on the treatment of liver fibrosis. However, the mechanism of RGXJD cures liver fibrosis requires further elucidation.Methods: In this work, the therapeutic effect of RGXJD on CCl4-induced liver fibroses serum and liver tissue metabolite changes in rat was analyzed by 1H-NMR metabolomics. Meanwhile, histopathology examinations and serum clinical chemistry analysis verified the experimental results of metabolomics.Results: RGXJD treatment could reverse the increase in ALT and AST induced by CCl4 and attenuate the pathological changes in liver tissue. In the 1H-NMR metabolomic analysis, PLS-DA score plots demonstrated that the serum and liver tissue metabolic profiles in rats of the RGXJD groups were similar those of the control group, yet remarkably apart from the CCl4 group. The mechanism may be related to the endogenous metabolites including energy metabolism, amino acid metabolism, TCA cycle and purine metabolism in rats. Correlation analysis were then performed to further confirm the metabolites involved in Isoleucine, Tyrosine, UDP-Glucose, Glutathione and Leucine, etc.Conclusions: These findings may provided new insights into the mechanism of the hepatoprotection of RGXJD.

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