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1.
Molecules ; 24(6)2019 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-30901924

RESUMO

BACKGROUND: Flavonoids with various structures play a vital role in plant acclimatization to varying environments as well as in plant growth, development, and reproduction. Exogenous applications of ethylene and 1-aminocyclopropane carboxylic acid (ACC), could affect the accumulation of flavonoids. Very few attempts have been made to investigate the effect of 1-aminocyclopropane carboxylic acid oxidase (ACO), a unique enzyme that catalyzes ACC to ethylene, on genes and metabolites in the flavonoid biosynthetic pathway. In this study, two ACOs in safflower (CtACOs) were cloned, and then transgenic safflower with overexpressed CtACO1 was generated through the Agrobacterium-mediated floral dipping method. RESULTS: CtACO1 and CtACO2 were both characterized by the 2-oxoglutarate binding domain RxS and the ferrous iron binding site HxDxnH as ACOs from other plants. However, the transcript levels of CtACO1 in flowers at stages I, II, III, and IV were all higher than those of CtACO2. At the cellular level, by using electroporation transformation, CtACO1 was found to be localized at the cytomembrane in onion epidermal cells. CtACO1 overexpression had varying effects on genes involved in the ethylene and flavonoid biosynthetic pathways. The metabolites analysis showed that CtACO1 overexpression lines had a higher accumulation of quercetin and its glycosylated derivatives (quercetin 3-ß-d-glucoside and rutin). In contrast, the accumulation of quinochalcones (hydroxysafflor yellow A and carthamin), kaempferol glycosylated derivatives (kaempferol-3-O-ß-rutinoside and kaempferol-3-O-ß-d-glucoside), apigenin, and luteolin in CtACO1 overexpression lines were decreased. CONCLUSION: This study confirmed the feasibility of applying the floral dipping method to safflower and showed a novel regulatory effect of CtACO1 in the flavonoid biosynthetic pathway. It provides hypothetical and practical groundwork for further research on regulating the overall metabolic flux of flavonoids in safflower, particularly hydroxysafflor yellow A and other quinochalcones, by using appropriate genetic engineering strategies.


Assuntos
Ácidos Carboxílicos/metabolismo , Carthamus tinctorius/genética , Carthamus tinctorius/metabolismo , Flavonoides/metabolismo , Oxirredutases/genética , Sequência de Aminoácidos , Vias Biossintéticas , Carthamus tinctorius/química , Bases de Dados Genéticas , Perfilação da Expressão Gênica , Metaboloma , Metabolômica , Oxirredutases/metabolismo , Transporte Proteico
2.
Biosci Rep ; 39(2)2019 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-30737304

RESUMO

Nephrolithiasis is one of the world's major public health burdens with a high incidence and a risk of persistent renal dysfunction. Fu-Fang-Jin-Qian-Chao granules (FFJQC), a traditional Chinese herb formula, is commonly used in treatment of nephrolithiasis. However, the therapeutic mechanism of FFJQC on kidney stone has still been a mystery. The objective of the present study is to explore the therapeutic mechanism of FFJQC on kidney injury and identify unique metabolomics patterns using a mouse model of kidney stone induced by a calcium oxalate (CaOx) deposition. Von Kossa staining and immuno-histopathological staining of osteopontin (OPN), cluster of differentiation 44 (CD44) and calbindin-D28k were conducted on renal sections. Biochemical analysis was performed on serum, urine, and kidney tissues. A metabolomics approach based on ultra-HPLC coupled with quadrupole-TOF-MS (UHPLC-Q-TOF/MS) was used for serum metabolic profiling. The immunohistopathological and biochemical analysis showed the therapeutic benefits of FFJQC. The expression levels of OPN and CD44 were decreased while calbindin-D28k increased after the CaOx injured mice were treated with FFJQC. In addition, total of 81 serum metabolites were identified to be associated with protective effects of FFJQC on CaOx crystal injured mice. Most of these metabolites were involved in purine, amino acid, membrane lipid and energy metabolism. Potential metabolite biomarkers were found for CaOx crystal-induced renal damage. Potential metabolite biomarkers of CaOx crystal-induced renal damage were found. FFJQC shows therapeutic benefits on CaOx crystal injured mice via regulation of multiple metabolic pathways including amino acids, purine, pyrimidine, glycerolipid, arachidonic acid (AA), sphingolipid, glycerophospholipid, and fatty acid.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Cálculos Renais/tratamento farmacológico , Rim/efeitos dos fármacos , Metaboloma/efeitos dos fármacos , Substâncias Protetoras/uso terapêutico , Animais , Oxalato de Cálcio/efeitos adversos , Modelos Animais de Doenças , Rim/metabolismo , Rim/patologia , Cálculos Renais/etiologia , Cálculos Renais/metabolismo , Cálculos Renais/patologia , Masculino , Metabolômica , Camundongos Endogâmicos C57BL
3.
Artigo em Inglês | MEDLINE | ID: mdl-30099286

RESUMO

Nephrolithiasis is a systemic metabolic disease with a worldwide incidence that is increasing yearly, as well as a high recurrence rate; however, this disease's pathogenesis has not been thoroughly elucidated to date. Several epidemiological studies have shown that the risk for developing kidney stones increases in people with dyslipidemia. To explore the mechanism of lipid-induced kidney stones, we established a mouse model for renal urolithiasis based on intraperitoneal injections of glyoxylate (120 mg/kg/d). Lipidomics based on ultra high performance liquid chromatography coupled with quadrupole-time of flight mass spectrometry (UPLC-QTOF-MS/MS) was performed to determine the changes in lipid metabolism in serum and kidneys. We screened 179 and 196 different lipid metabolites in the kidneys and serum, respectively, including fatty acyls, glycerophospholipids, sphingolipids, glycerolipids and prenol lipids. We found that polyunsaturated fatty acids, such as arachidonic acid, eicosapentaenoic acid, and docosahexoenoic acid, and ceramides and lysophosphocholines mediated inflammatory responses and that the oxidative stress induced by oleylethanolamine and glycerophosphoethanolamine plasmalogens is closely related to the development of kidney stones. These results provide strong evidence for the relationship between lipid metabolism and the development of kidney stones and suggest a clear direction for future research.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Lipídeos/análise , Metabolômica/métodos , Nefrolitíase/metabolismo , Espectrometria de Massas em Tandem/métodos , Animais , Glioxilatos/efeitos adversos , Rim/química , Metabolismo dos Lipídeos , Lipídeos/sangue , Lipídeos/química , Lipídeos/classificação , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Nefrolitíase/sangue , Nefrolitíase/induzido quimicamente , Estresse Oxidativo
4.
Front Pharmacol ; 9: 620, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29950996

RESUMO

Purpose: As a Chinese medicinal herb, Desmodium styracifolium (Osb.) Merr (DS) has been applied clinically to alleviate crystal-induced kidney injuries, but its effective components and their specific mechanisms still need further exploration. This research first combined the methods of network pharmacology and proteomics to explore the therapeutic protein targets of DS on oxalate crystal-induced kidney injuries to provide a reference for relevant clinical use. Methods: Oxalate-induced kidney injury mouse, rat, and HK-2 cell models were established. Proteins differentially expressed between the oxalate and control groups were respectively screened using iTRAQ combined with MALDI-TOF-MS. The common differential proteins of the three models were further analyzed by molecular docking with DS compounds to acquire differential targets. The inverse docking targets of DS were predicted through the platform of PharmMapper. The protein-protein interaction (PPI) relationship between the inverse docking targets and the differential proteins was established by STRING. Potential targets were further validated by western blot based on a mouse model with DS treatment. The effects of constituent compounds, including luteolin, apigenin, and genistein, were investigated based on an oxalate-stimulated HK-2 cell model. Results: Thirty-six common differentially expressed proteins were identified by proteomic analysis. According to previous research, the 3D structures of 15 major constituents of DS were acquired. Nineteen differential targets, including cathepsin D (CTSD), were found using molecular docking, and the component-differential target network was established. Inverse-docking targets including p38 MAPK and CDK-2 were found, and the network of component-reverse docking target was established. Through PPI analysis, 17 inverse-docking targets were linked to differential proteins. The combined network of component-inverse docking target-differential proteins was then constructed. The expressions of CTSD, p-p38 MAPK, and p-CDK-2 were shown to be increased in the oxalate group and decreased in kidney tissue by the DS treatment. Luteolin, apigenin, and genistein could protect oxalate-stimulated tubular cells as active components of DS. Conclusion: The potential targets including the CTSD, p38 MAPK, and CDK2 of DS in oxalate-induced kidney injuries and the active components (luteolin, apigenin, and genistein) of DS were successfully identified in this study by combining proteomics analysis, network pharmacology prediction, and experimental validation.

5.
Sci Rep ; 8(1): 5423, 2018 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-29615664

RESUMO

Polybrominated diphenyl ethers (PBDEs) may affect male reproductive function. 4-bromodiphenyl ether (BDE-3), the photodegradation products of higher brominated PBDEs, is the most fundamental mono-BDE in environment but is less studied. The purpose of this study was to investigate the reproductive toxicity induced by BDE-3 and explore the mechanism by metabolomics approach. In this study, mice were treated intragastrically with BDE-3 for consecutive six weeks at the dosages of 0.0015, 1.5, 10 and 30 mg/kg. The reproductive toxicity was evaluated by sperm analysis and histopathology examinations. UPLC-Q-TOF/MS was applied to profile the metabolites of testis tissue, urine and serum samples in the control and BDE-3 treated mice. Results showed the sperm count was dose-dependently decreased and percentage of abnormal sperms increased by the treatment of BDE-3. Histopathology examination also revealed changes in seminiferous tubules and epididymides in BDE-3 treated mice. Metabolomics analysis revealed that different BDE-3 groups showed metabolic disturbances to varying degrees. We identified 76, 38 and 31 differential metabolites in testis tissue, urine and serum respectively. Pathway analysis revealed several pathways including Tyrosine metabolism, Purine metabolism and Riboflavin metabolism, which may give a possible explanation for the toxic mechanism of BDE-3. This study indicates that UHPLC-Q-TOFMS-based metabolomics approach provided a better understanding of PBDEs-induced toxicity dynamically.


Assuntos
Éteres Difenil Halogenados/toxicidade , Metabolômica , Reprodução/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Tamanho do Órgão/efeitos dos fármacos , Contagem de Espermatozoides , Testículo/efeitos dos fármacos , Testículo/patologia , Testículo/fisiologia
6.
Biomed Chromatogr ; 32(6): e4208, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29431198

RESUMO

This study aimed to investigate the efficacy of mangiferin, including its known antioxidant and anti-inflammatory effects on sepsis-induced lung injury induced by a classical cecal ligation and puncture (CLP) models in mouse using a metabolomics approach. A total of 24 mice were randomly divided into four groups: the sham group was given saline before sham operation. The CLP group received the CLP operation only. HMF and LMF groups were given mangiferin treatment of high dose and low dose of mangiferin, respectively, before the CLP operation. One week after treatment, the mice were sacrificed and their lungs were collected for metabolomics analysis. We developed ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry to perform lung metabolic profiling analysis. With the methods of principal component analysis and partial least squares discriminant analysis, 58 potential metabolites associated with amino acid metabolism, purine metabolism, lipid metabolism and energy regulation were observed to be increased or reduced in HMF and LMF groups compared with the CLP group. Conclusively, our results suggest that mangiferin plays a protective role in the moderation of sepsis-induced lung injury through reducing oxidative stress, regulating lipid metabolism and energy biosynthesis.


Assuntos
Antioxidantes/farmacologia , Lesão Pulmonar/metabolismo , Metaboloma/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Sepse/metabolismo , Xantonas/farmacologia , Animais , Antioxidantes/administração & dosagem , Cromatografia Líquida de Alta Pressão , Modelos Animais de Doenças , Pulmão/efeitos dos fármacos , Pulmão/patologia , Lesão Pulmonar/patologia , Masculino , Espectrometria de Massas , Metabolômica , Camundongos , Camundongos Endogâmicos ICR , Xantonas/administração & dosagem
7.
J Proteome Res ; 17(1): 656-669, 2018 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-29190102

RESUMO

Vascular depression (VD), a subtype of depression, is caused by vascular diseases or cerebrovascular risk factors. Recently, the proportion of VD patients has increased significantly, which severely affects their quality of life. However, the current pathogenesis of VD has not yet been fully understood, and the basic research is not adequate. In this study, on the basis of the combination of LC-MS-based proteomics and metabolomics, we aimed to establish a protein metabolism regulatory network in a murine VD model to elucidate a more comprehensive impact of VD on organisms. We detected 44 metabolites and 304 proteins with different levels in the hippocampus samples from VD mice using a combination of metabolomic and proteomics analyses with an isobaric tags for relative and absolute quantification (iTRAQ) method. We constructed a protein-to-metabolic regulatory network by correlating and integrating the differential metabolites and proteins using ingenuity pathway analysis. Then we quantitatively validated the levels of the bimolecules shown in the bioinformatics analysis using LC-MS/MS and Western blotting. Validation results suggested changes in the regulation of neuroplasticity, transport of neurotransmitters, neuronal cell proliferation and apoptosis, and disorders of amino acids, lipids and energy metabolism. These proteins and metabolites involved in these dis-regulated pathways will provide a more targeted and credible direction to study the mechanism of VD. Therefore, this paper presents an approach and strategy that was applied in integrative proteomics and metabolomics for research and screening potential targets and biomarkers of VD, which could be more precise and credible in a field lacking adequate basic research.


Assuntos
Depressão/etiologia , Metabolômica/métodos , Proteômica/métodos , Animais , Biomarcadores , Cromatografia Líquida , Biologia Computacional , Hipocampo/química , Redes e Vias Metabólicas , Camundongos , Espectrometria de Massas em Tandem , Doenças Vasculares
8.
Toxicol Mech Methods ; 27(9): 687-696, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28701067

RESUMO

Veratrum nigrum L. (VN) is a poisonous traditional Chinese medicine herb present since thousands of years in China. Clinical studies have shown that VN has the ability to cause hepatotoxicity, which severely limits its clinical use. The mechanism of its hepatotoxicity has not been fully elucidated. The purpose of this study was to develop and characterize a model of acute and chronic hepatotoxicity induced by Veratrum nigrum L. extract (VNE) to understand the mechanism of liver tissue metabolomics approach using on ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOFMS). Mice were administered with VNE in the acute and chronic phases. Histopathologic inspections and biochemistry analysis disclosed severe liver damage after exposure to VNE. A partial least-squares discriminant analysis (PLS-DA) of the metabolomic profiles of rat liver tissues highlighted a number of metabolic disturbances induced by VNE, focusing on purine and pyrimidine metabolism, tryptophan metabolism, phospholipid metabolism, sphingolipid metabolism and fatty acid metabolism. These findings could well explain VNE-induced acute and chronic hepatotoxicity and reveal several potential biomarkers associated with this toxicity. This indicates that UHPLC-Q-TOFMS-based metabolomics approach demonstrated its feasibility and allowed a better understanding of VNE-induced liver toxicity dynamically.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Fígado/efeitos dos fármacos , Espectrometria de Massas/métodos , Metabolômica , Extratos Vegetais/toxicidade , Veratrum/química , Animais , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL
9.
Biomed Chromatogr ; 31(12)2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28544073

RESUMO

The acute cardiotoxicity induced by Veratrum nigrum (VN) is explored by analyzing heart tissue metabolic profiles in mouse models and applying reversed-phase liquid chromatography mass spectrometry and hydrophilic interaction liquid chromatography mass spectrometry that are based on ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry. An animal model of acute heart injury was established in mice via intra-gastric administration of VN. Then, electrocardiogram and echocardiograph monitoring of cardiac function and pathological examination were performed on mice in both the control and VN groups, and it was verified that acute heart injury was caused. Meanwhile, comparing the results of the control and VN groups, we detected 36 differential endogenous metabolites of heart tissue, including taurine, riboflavin, purine and lipids, which are related to many possible pathways such as purine metabolism, taurine and hypotaurine metabolism and energy metabolism. Our study provides a scientific approach for evaluating and revealing the mechanisms of VN-induced cardiotoxicity via the metabolomic strategy.


Assuntos
Cardiotoxinas/toxicidade , Cromatografia Líquida de Alta Pressão/métodos , Metaboloma/efeitos dos fármacos , Extratos Vegetais/toxicidade , Veratrum/química , Animais , Cardiotoxicidade/metabolismo , Cardiotoxinas/química , Modelos Animais de Doenças , Coração/efeitos dos fármacos , Interações Hidrofóbicas e Hidrofílicas , Masculino , Espectrometria de Massas/métodos , Redes e Vias Metabólicas , Metabolômica/métodos , Camundongos , Camundongos Endogâmicos C57BL , Miocárdio/metabolismo , Miocárdio/patologia , Extratos Vegetais/química
10.
Biomed Chromatogr ; 31(6)2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28058725

RESUMO

The aim of this study was to demonstrate the differences of metabolomics changes in a hyperalgesia model and find potent biomarkers of hyperalgesia. Seven rats were placed in metabolic cages. An emulsion containing 500 µg of Complete Freund's adjuvant (CFA) was used to induce hyperalgesia. Urine samples were collected prior to the injection of CFA and on post-injection days 1, 3 and 7. Ultraperformance liquid chromatography, coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF/MS), was used for a quantitative analysis of urinary metabolic changes in the CFA-induced hyperalgesia model. Differences between the metabolic profiles of the rats in the four groups were analyzed using partial least squares discriminant analysis. Thirty-four potential urine metabolite biomarkers were identified, which changed in a trend similar to the pain threshold. These potential biomarkers were involved in 11 metabolic pathways, as follows: alanine, aspartate, and glutamate metabolism; ascorbate and aldarate metabolism; glycerolipid metabolism; glycerophospholipid metabolism; histidine metabolism; phenylalanine metabolism; sphingolipid metabolism; tryptophan metabolism; tyrosine metabolism; valine, leucine and isoleucine biosynthesis; and vitamin B6 metabolism. These results may improve our understanding of hyperalgesia and provide a basis for the clinical diagnosis of hyperalgesia.


Assuntos
Adjuvante de Freund/toxicidade , Hiperalgesia/induzido quimicamente , Metabolômica , Urina , Animais , Biomarcadores/urina , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas , Ratos , Ratos Sprague-Dawley
11.
Sci Rep ; 7: 40035, 2017 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-28059131

RESUMO

Sepsis, in addition to causing fatality, is an independent risk factor for cognitive impairment among sepsis survivors. The pathologic mechanism of endotoxemia induced acute neuro-inflammation still has not been fully understood. For the first time, we found the disruption of neurotransmitters 5-HT, impaired neurogenesis and activation of astrocytes coupled with concomitant neuro-inflammation were the potential pathogenesis of endotoxemia induced acute neuro-inflammation in sepsis survivors. In addition, dioscin a natural steroidal saponin isolated from Chinese medicinal herbs, enhanced the serotonergic system and produced anti-depressant effect by enhancing 5-HT levels in hippocampus. What is more, this finding was verified by metabolic analyses of hippocampus, indicating 5-HT related metabolic pathway was involved in the pathogenesis of endotoxemia induced acute neuro-inflammation. Moreover, neuro-inflammation and neurogenesis within hippocampus were indexed using quantitative immunofluorescence analysis of GFAP DCX and Ki67, as well as real-time RT-PCR analysis of some gene expression levels in hippocampus. Our in vivo and in vitro studies show dioscin protects hippocampus from endotoxemia induced cascade neuro-inflammation through neurotransmitter 5-HT and HMGB-1/TLR4 signaling pathway, which accounts for the dioscin therapeutic effect in behavioral tests. Therefore, the current findings suggest that dioscin could be a potential approach for the therapy of endotoxemia induced acute neuro-inflammation.


Assuntos
Diosgenina/análogos & derivados , Encefalite/tratamento farmacológico , Endotoxemia/complicações , Neurogênese/efeitos dos fármacos , Agonistas do Receptor de Serotonina/metabolismo , Serotonina/metabolismo , Animais , Diosgenina/metabolismo , Perfilação da Expressão Gênica , Proteína Glial Fibrilar Ácida/análise , Hipocampo/patologia , Hipocampo/fisiologia , Antígeno Ki-67/análise , Camundongos Endogâmicos C57BL , Microscopia de Fluorescência , Proteínas Associadas aos Microtúbulos/análise , Neuropeptídeos/análise , Reação em Cadeia da Polimerase em Tempo Real
12.
J Pharm Biomed Anal ; 128: 469-479, 2016 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-27371920

RESUMO

The herbal pair Zhimu-Baihe (Zhimu: Anemarrhena asphodeloides; Baihe: Lilium brownii var. viridulum) is a traditional Chinese medicament used for the treatment of depression. However, the relevant mechanisms of action has not been clarified. This study investigated the anti-depressant activity of the total saponins from Zhimu and Baihe and the mechanisms underlying using a chronic unpredictable mild stress (CUMS)-induced rat model of depression. High performance liquid chromatography with electrochemical detection (HPLC-ECD) was applied to determine the levels of three monoamine neurotransmitters, 5-hydroxytryptamine (5-HT), noradrenaline (NE) and dopamine (DA), in the rat hippocampus. Optimized pretreatment of samples and mass spectrometry conditions were used to analyse the metabonomic profile of the hippocampus. The 5-HT and NE levels in the CUMS group were reduced compared with the control group, whereas all groups had similar DA levels. The metabonomic profile of the hippocampus revealed 32 differential metabolites between the CUMS and control group, among which 18 metabolites were significantly recovered in the Anemarrhena saponins and Lilium saponins (AL) combination intervention group. These results suggested an anti-depressant effect of AL. Moreover, 24 metabolites in AL group were better recovered compared with the Anemarrhena saponins (AS) or Lilium saponins (LS) intervention groups, suggesting a synergetic effect of AS and LS in the treatment of depression. The anti-depressant effect might be related to the regulation of several metabolic pathways, including monoamine neurotransmitter synthesis (especially 5-HT and NE), and amino acid, fatty acid, and phospholipid metabolism in rats.


Assuntos
Depressão/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Metabolômica , Saponinas/farmacologia , Animais , Antidepressivos/farmacologia , Modelos Animais de Doenças , Dopamina/metabolismo , Hipocampo/metabolismo , Masculino , Norepinefrina/metabolismo , Ratos , Serotonina/metabolismo
13.
Sci Rep ; 6: 30142, 2016 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-27443631

RESUMO

About 80% of kidney stones are composed of calcium oxalate (CaOx) with variable amounts of calcium phosphate, and hyperoxaluria is considered as an important factor of CaOx nephrolithiasis. However, the underlying metabolic mechanisms of CaOx nephrolithiasis remain undefined. In this study, we successfully developed a rat model with hydroxy-L-proline (HLP) -induced CaOx nephrolithiasis. Rats were continuously orally administrated with HLP for 28 days. Urine and blood samples were collected from the rats treated with or without HLP at four different time points. UPLC-Q-TOF/MS was applied to profile the abundances of metabolites. To obtain more comprehensive analysis of metabolic profiling spectrum, combination of RP-LC and HILIC were applied. We identify 42 significant differential metabolites in the urine, and 13 significant differential metabolites in the blood. Pathway analysis revealed that the pathways involved in amino acid metabolism, taurine metabolism, bile acid synthesis, energy metabolism, TCA cycle, purine metabolism, vitamin metabolism, nicotinic acid and nicotinamide metabolism have been modulated by HLP treatment. This study suggested that a number of metabolic pathways are dysfunctional in the HLP induced crystal kidney injury, and further studies on those pathways are warranted to better understand the metabolic mechanism of CaOx nephrolithiasis.

14.
Int J Clin Exp Pathol ; 8(3): 2680-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26045773

RESUMO

The aim of this study is to evaluate the protective effect and underlying mechanism of hydrogen gas (H2) to glyoxylate induced renal calcium oxalate (CaOx) crystal deposition in mice. In present work, rodent renal CaOx crystal deposition model was introduced by intra-abdominal injection of glyoxylate (100 mg/kg/d) for 5 days. Two days before administration of glyoxylate, inhalation of H2 for 30 min per day was initiated and continued for 7 days. By the end of the study, the samples of 24 hours urine, serum and renal tissue were collected for biochemical and pathological assay. According to levels of urine calcium excretion, renal calcium deposition, a serum excretion of kidney injury molecule-1 (KIM-1) assay and a TUNEL assay, inhalation of H2 could successfully decrease the CaOx crystallizations and protect against renal injury. Crystal deposition in the kidneys is associated with oxidative stress, which was indicated by increased levels of renal malondialdehyde (MDA) and 8-hydroxydeoxyguanosine (8-OHdG) and decreased activities of superoxide dismutase (SOD), glutathione (GSH) and catalase (CAT). These effects were reversed by a high-dose H2 pretreatment. The renal expressions of osteopontin (OPN), CD44, monocyte chemoattractant protein-1 (MCP-1) and interleukin-10 (IL-10) were markedly increased in glyoxylate-treated mice, and H2 significantly attenuated the increase of OPN, CD44 and MCP-1 but upregulated the expression of IL-10. Our findings demonstrate that inhalation of H2 reduces renal crystallization, renal oxidative injury and inflammation and it may be a candidate agent with few adverse effects for prevention of nephrolithiasis.


Assuntos
Hidrogênio/administração & dosagem , Rim/efeitos dos fármacos , Nefrolitíase/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Administração por Inalação , Animais , Apoptose/efeitos dos fármacos , Modelos Animais de Doenças , Glioxilatos/toxicidade , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Rim/metabolismo , Rim/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL
15.
J Ethnopharmacol ; 166: 323-32, 2015 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-25794803

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Orthosiphon stamineus (OS), a traditional Chinese herb, is often used for promoting urination and treating nephrolithiasis. AIM OF THE STUDY: Urolithiasis is a major worldwide public health burden due to its high incidence of recurrence and damage to renal function. However, the etiology for urolithiasis is not well understood. Metabonomics, the systematic study of small molecule metabolites present in biological samples, has become a valid and powerful tool for understanding disease phenotypes. In this study, a urinary metabolic profiling analysis was performed in a mouse model of renal calcium oxalate crystal deposition to identify potential biomarkers for crystal-induced renal damage and the anti-crystal mechanism of OS. MATERIALS AND METHODS: Thirty six mice were randomly divided into six groups including Saline, Crystal, Cystone and OS at dosages of 0.5g/kg, 1g/kg, and 2g/kg. A metabonomics approach using ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) was developed to perform the urinary metabolic profiling analysis. Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were utilized to identify differences between the metabolic profiles of mice in the saline control group and crystal group. RESULTS: Using partial least squares-discriminant analysis, 30 metabolites were identified as potential biomarkers of crystal-induced renal damage. Most of them were primarily involved in amino acid metabolism, taurine and hypotaurine metabolism, purine metabolism, and the citrate cycle (TCA). After the treatment with OS, the levels of 20 biomarkers had returned to the levels of the control samples. CONCLUSIONS: Our results suggest that OS has a protective effect for mice with crystal-induced kidney injury via the regulation of multiple metabolic pathways primarily involving amino acid, energy and choline metabolism.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Nefropatias/tratamento farmacológico , Nefropatias/metabolismo , Rim/efeitos dos fármacos , Metaboloma/efeitos dos fármacos , Orthosiphon/química , Urina/química , Animais , Biomarcadores/metabolismo , Oxalato de Cálcio/farmacologia , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/química , Etnofarmacologia/métodos , Rim/metabolismo , Nefropatias/induzido quimicamente , Masculino , Medicina Tradicional Chinesa/métodos , Metabolômica/métodos , Camundongos , Camundongos Endogâmicos C57BL
16.
J Clin Biochem Nutr ; 55(3): 184-90, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25411524

RESUMO

The anti-nephrolithiasis effect of Xue Niao An (XNA) capsules is explored by analyzing urine metabolic profiles in mouse models, with ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). An animal model of calcium oxalate crystal renal deposition was established in mice by intra-abdominal injection of glyoxylate. Then, treatment with XNA by intra-gastric administration was performed. At the end of the study, calcium deposition in kidney was measured by Von Kossa staining under light microscopy, and the Von Kossa staining changes showed that XNA significantly alleviated the calcium oxalate crystal deposition. Meanwhile, urine samples for fifteen metabolites, including amino acids and fatty acids, with significant differences were detected in the calcium oxalate group, while XNA treatment attenuated metabolic imbalances. Our study indicated that the metabonomic strategy provided comprehensive insight on the metabolic response to XNA treatment of rodent renal calcium oxalate deposition.

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