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metabonomics study of liver and kidney subacute toxicity induced by garidi-5 in rats

Chinese Herbal Medicines 2022年第3期14卷 422-431页

作者： Wurihan Aodungerle Bilige Lili Sirguleng Aduqinfu Meirong Bai Key Laboratory of Mongolian Medicine Research and Development Engineering Ministry EducationInner Mongolia Minzu UniversityTongliao 028000China Mongolian Medical College Inner Mongolia Minzu UniversityTongliao 028000China Tongliao City Hospital of Inner Mongolia Tongliao 028000China School of Nursing Inner Mongolia Minzu UniversityTongliao 028000China

Objective:metabonomics was used to analyze and explore the biomarkers and possible mechanisms of liver and kidney subacute toxicity induced by garidi-5 in rats.Methods:Taking garidi-5 as the target drug and SD rats as the research objects,each administration group except the normal group was intragastric administration of the corresponding drug solution for28 d.The serum,liver and kidney samples of rats were detected by metabolomics and characterized by principal component analysis(PCA)and partial least squares discriminant analysis(PLS-DA)to identify the sensitive markers and metabolic pathways of liver and kidney subacute toxicity.Results:Metabolomics analysis showed that compared with the normal group(Z),the 52,64 and 54 different metabolites were identified in the serum,liver and kidney samples of garidi-5 high dose group(GG),which were mainly enriched in ABC transporters,arginine and proline metabolism,nicotinate and nicotinamide metabolism,central carbon metabolism in cancer pathways.Conclusion:The preliminarily suggested that garidi-5 can damage the liver and kidney by affecting the ABC transporters,arginine and proline metabolism,nicotinate and nicotinamide metabolism pathways,etc.Trimethylamine N-oxide,L-pyroglutamic acid,glycine-betaine,xanthine,glutathione,L-leucine,cytidine,L-arginine,spermidine,urea,5-aminovaleric acid,creatine,L-glutamic acid,1-methylnicotinamide and S-adenosyl-L-methionine can be used as potential biomarkers of liver and kidney toxicity sensitivity.

关键词： garidi-5 kidney liver metabonomics subacute toxicity

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metabonomics:A Useful Tool to Reveal Underlying Relationships between Altered Chinese Medicine Syndromes and Ultrafiltration in Treatment of Heart Failure

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Chinese Journal of Integrative Medicine 2021年第4期27卷 259-264页

作者： GUO Li-jun CHEN Ke-ji SUN Ming-qian WANG An-zhu GAO Feng ZHENG Yuan MA Xiao-chang Graduate School of Beijing University of Chinese Medicine Beijing(100029)China Cardiovascular Disease Center Xiyuan HospitalChina Academy of Chinese Medical SciencesBeijing(100091)China Institute of Basic Medicine Xiyuan HospitalChina Academy of Chinese Medical SciencesBeijing(100091)China

Objective:To reveal the underlying relationships between Chinese medicine(CM)syndromes and ultrafiltration(UF)in the treatment of heart failure based on a metabonomic approach.Methods:Seventeen acute decompensated heart failure(ADHF)patients were enrolled,and their CM syndromes before and after UF were collected.In addition,their venous plasma collected before and after UF was used for liquid chromatographmass spectrometer-based metabonomic analysis.Both reversed phase liquid chromatography and hydrophilic interaction liquid chromatography were used to analyze the plasma samples.Partial least-squares to latent structure-discriminant analyses were used for data analysis.Results:An obvious difference was observed preand post-treatment.A total of 17 potential biomarkers associating with alterd syndromes with UF including hypoxanthine,1-methylhistidine,phytosphingosine,O-decanoyl-R-carnitine,etc.were screened out,showing a significant change after UF.The major adjusted m etabolic pathways were purine metabolism,histidine metabolism,leucine and isoleucine metabolism,arginine and proline metabolism,carnitine shuttle,sphingolipid metabolism and phospholipid metabolism.Conclusions:Metabonomic approach is a useful tool to identify potential biomarkers of altered syndromes link to UF and could provide a theoretical basis for further research on the therapeutic mechanism of UF combined with CM.

关键词： metabonomics heart failure ultrafiltration Chinese medicine

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metabonomics delineates allergic reactions induced by Shuang-huang-lian injection in rats using ultra performance liquid chromatography-mass spectrometry

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Chinese Journal of Natural Medicines 2018年第8期16卷 628-640页

作者： GU Yuan-Yuan SHI Lang ZHANG Dan-Dan HUANG Xin CHEN Da-Zhong Research Institute of Traditional Chinese Medicine Heilongjiang University of Chinese Medicine First Clinical Medical College Heilongjiang University of Chinese Medicine

Shuang-huang-lian Injection(SHLI) is the first successfully developed drug from traditional Chinese medicine(TCM) powder for injection,since its use for the treatment of acute respiratory tract infection,pneumonia,influenza,etc.At the same time,its allergic reactions have also emerged,which limits clinical applications.However,few scholars pay attention to the mechanism of allergic reactions.In this present study,metabonomics technology was used to explore the changes in endogenous metabolites in urine of the rat model of SHLI induced allergic reaction;we and analyzed the metabolites,metabolic pathway,and the mechanism which were closely related to the allergic reactions.The levels of serum histamine and tryptase were examined and changes in histomorphology were also observed.Based on the UPLC-Q-TOF/MS metabonomics,we carried out the pattern recognition analysis,selected potential biomarkers associated with allergic reactions,and explored the pathological mechanism for SHLI induced allergic reaction,which laid the foundation for the safety research of SHLI.Our results showed that SHLI increased the levels of serum histamine and tryptase in rats with allergic reaction;we determined 15 biomarkers in rat allergic reaction model induced by SHLI and found multiple metabolic pathways involved,such as metabolism of linolenic acid,phenylalanine,amino acid,2-oxo acid,and purine and other metabolic pathways.

关键词： Shuang-huang-lian injection Biomarker metabonomics Allergic mechanism Metabolites

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Heat stroke alters hippocampal and cerebellar transmitter metabonomics

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World Journal of Emergency Medicine 2023年第4期14卷 287-293页

作者： Guoxin He Ancong Xu Xichong Yu Fan Huang Lei Su The First School of Clinical Medicine Southern Medical UniversityGuangzhou 510515China Department of Critical Care Medicine the Third Affiliated Hospital of Wenzhou Medical UniversityWenzhou 325000China School of Pharmaceutical Sciences Wenzhou Medical UniversityWenzhou 325035China

BACKGROUND:The mechanisms underlying heat stroke(HS)-induced hippocampal injury remain unclear.This study aimed to evaluate the HS-induced metabonomics of hippocampal and cerebellar transmitters.METHODS:The HS model was established with male Sprague-Dawley rats subjected to heat exposure of up to 42℃ at a humidity of(55.0±5.0)%.The hippocampal and cerebellar transmitters and metabolites of rats were tested via ultra-high-performance liquid chromatography–mass spectrometry(UPLC-MS/MS).The primary transmitters and metabolites were identified by principal component analysis(PCA)and orthogonal partial least square-discriminant analysis(OPLS-DA).The major metabolic pathways for HS were selected after enrichment.The brain injury was evaluated by histological tests.RESULTS:HS induced hippocampal and cerebellar injuries in rats.HS upregulated the protein levels of hippocampal glutamate,glutamine,gamma-aminobutyric acid,L-tryptophan(Trp),5-hydroxy-indoleacetic acid,and kynurenine;however,it downregulated asparagine,tryptamine,5-hydroxytryptophan,melatonin,3,4-dihydroxyphenylalanine(L-DOPA),and vanillylmandelic acid.HS also sharply elevated the protein levels of cerebellar methionine and Trp,and decreased the levels of serotonin,L-alanine,L-asparagine,L-aspartate,cysteine,norepinephrine,spermine,spermidine,and tyrosine.Hippocampal glutamate,monoamine transmitters,cerebellar aspartate acid,and catecholamine transmitters’metabolic pathways were identified as the main metablic pathways in HS.CONCLUSION:The hippocampus and cerebellum were injured in rats with HS,possibly induced the disorder of hippocampal glutamate and serotonin metabolism,cerebellar aspartate acid and catecholamine transmitter metabolism,and related metabolic pathways.

关键词： Heat stroke Transmitters Rat Hippocampus Cerebellum metabonomics

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Analgesic Activity of Jin Ling Zi Powder and Its Single Herbs:A Serum metabonomics Study

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Chinese Journal of Integrative Medicine 2022年第11期28卷 1007-1014页

作者： WANG Cui-fang CAI Xiao-rong CHI Yan-ni MIAO Xiao-yao YANG Jian-yun XIAO Bing-kun HUANG Rong-qing Institute of Radiation Medicine Academy of Military Medical SciencesBeijing(100850)China School of Chinese Medicine Guangdong Pharmaceutical UniversityGuangzhou(510006)China School of Pharmacy Jiangxi University of Traditional Chinese MedicineNanchang(330000)China

Objective:To compare the analgesic effect of Jin Ling Zi Powder(JLZ)and its two single herbs.Methods:The hot plate method was used to induce pain.Totally 36 mice were randomly divided into 6 groups by a complete random design,including control,model,aspirin(ASP,0.14 g/kg body weight),JLZ(14 g/kg body weight),Corydalis yanhusuo(YHS,14 g/kg body weight),and Toosendan Fructus(TF,14 g/kg body weight)groups,6 mice in each group.The mice in the control and model groups were given the same volume of saline,daily for 2 consecutive weeks.At 30,60,90,and 120 min after the last administration,the pain threshold of mice in each group was measured,and the improvement rate of pain threshold was calculated.Serum endogenous metabolites were analyzed by gas chromatography–mass spectrometry(GC–MS).Results:There was no statistical difference in pain threshold among groups before administration(P>0.05).After 2 weeks of administration,compared with the model group,the pain threshold in JLZ,YHS,TF and ASP groups were increased to varying degrees(P<0.05).JLZ had the best analgesic effect and was superior to YHS and TF groups.A total of 14 potential biomarkers were screened in serum data analysis and potential biomarkers levels were all reversed to different degrees after the treatment with JLZ and its single herbs.These potential biomarkers were mainly related to glyoxylate and dicarboxylate metabolism,glycine,serine and threonine metabolism,valine,leucine and isoleucine biosynthesis,aminoacyl-t RNA biosynthesis and inositol phosphate metabolism.Conclusions:The analgesic mechanism of JLZ and YHS was mainly due to the combination of glycine and its receptor,producing post-synaptic potential,reducing the excitability of neurons,and weakening the afferent effect of painful information.

关键词： Jin Ling Zi Powder Chinese medicine metabonomics gas chromatography coupled to mass spectrometry analgesic Corydalis yanhusuo Toosendan Fructus

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metabonomics and Molecular Biology-based Effects of Sugemule-3 in an Isoproterenol-induced Cardiovascular Disease Rat Model

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Chemical Research in Chinese Universities 2018年第4期34卷 590-597页

作者： WANG Xiye WANG Yu WEI Chengxi YU Lijun Inner Mongolia Key Laboratory for the Natural Products Chemistry and Functional Molecular Synthesis College of Chemistry and Chemical Engineering Inner Mongolia University for the Nationalities Tongliao 028005 P. R. China Inner Mongolia Autonomous Region Key Laboratory of Mongolian Medicine Pharmacology for Cardio-cerebral Vascular System Medicinal Chemistry and Pharmacology Institute Inner Mongolia University for the Nationalities Tongliao 028005 R R. China

Cardiovascular disease（CVD） is a common and serious disease in the elderly, which has characteristically high prevalence, disability, and mortality rates. However, the etiology of CVD is still not very clear. The traditional Mongolian medicine Sugemule-3（SM） is usually used for the treatment of CVD and exhibits a good curative effect. In this study, a sentm metabolite profile analysis was used to identify potential biomarkers associated with isoprote- renol（ISO）-induced CVD and investigate the mechanism of the action of SM. Ultra-perfornlance liquid chromato- graphy coupled with quadrupole time-of-flight mass spectrometry（UPLC-Q-TOF-MS） was used for the metabono- mics analysis. Principal component analysis（PCA） was used to process the acquired data to differentiate the results of the control, CVD, and SM treatment groups. Orthogonal partial least squares discriminant analysis（OPLS-DA） enabled the identification of 21 metabolites as potential biomarkers that were relevant to phospholipid and energy metabolism. The results indicate that SM played a protective role against ISO-induced CVD in rats by regulating phospholipid and energy metabolic pathways. Fttrther, we verified the apoptotic metabolic pathway using molecular biology methods, such as terminal deoxynucleotidyl transferase（TdT） deoxyuridine 5＇-triphosphate（dUTP） nick-end labeling（TUNEL） assay and Western blot analysis. Furthermore, this study identified early biomarkers of CVD and elucidated the underlying mechanism of the therapeutic actions of SM, which is worth further to be investigated for development as a clinical therapy.

关键词： Sugemule-3 metabonomics Molecular biology Ultra-perfbrmance liquid chromatography coupled withmass spectrometry（UPLC-MS） Cardiovascular disease Isoproterenol

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Design and baseline data of a populationbased metabonomics study of eye diseases in eastern China: the Yueqing Ocular Diseases Investigation

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Eye and Vision 2020年第1期7卷 75-86页

作者： Yuxuan Deng Yuanbo Liang Sigeng Lin Liang Wen Jin Li Yue Zhou Meixiao Shen Jingwei Zheng Kemi Feng Yanting Sun Kwapong Willaim Robert Jia Qu Fan Lu Clinical and Epidemiological Research Center Eye Hospital of Wenzhou Medical University270 Xueyuan RoadWenzhou 325027ZhejiangChina School of Ophthalmology and Optometry Wenzhou Medical University270 Xueyuan RoadWenzhou 325027ZhejiangChina Qingdao Municipal Hospital 5 Donghai Middle RoadQingdao 266071ShandongChina Wuhu First People’s Hospital 1 Chizhushandong RoadWuhu 241000AnhuiChina Eye Hospital of Fushun City 1 Hupo RoadFushun 113006LiaoningChina Qilu Hospital of Shandong University(Qingdao) 758 Hefei RoadQingdao 266035ShandongChina

Background:China is undergoing a massive transition toward an urban and industrial economy.These changes will restructure the demographics and economy which will eventually influence the future patterns of disease.The risk factors of vision-impairing eye diseases remain ambiguous and poorly understood.Metabolomics is an ideal tool to understand and shed light on the ocular disease mechanisms for earlier treatment.This article aims to describe the design,methodology and baseline data of the Yueqing Ocular Diseases Investigation(YODI),a developed county population-based study to determine the prevalence and primary causes of visual impairment;also with metabonomics analysis we aimed to identify,predict and suggest some preventive biomarkers that cause blindness.Methods:A population-based,cross-sectional study.Randomized clustering sampling was used to identify adults aged 50 years and older in Xiangyang Town,Yueqing county-level City.The interviews covered demographic,behavioral,ocular risk factors and mental health state.The ocular examination included visual acuity,autorefraction,intraocular pressure,anterior and posterior segment examinations,fundus photography,retinal tomography and angiography,and visual field testing.Anthropometric measurements included height and weight,waist and hip circumference,blood pressure,pulse rate,electrocardiogram,and abdominal ultrasound scan.A venous blood sample was collected for laboratory tests and metabonomics studies.Results:Of the 5319 individuals recruited for the YODI,4769(89.7%)subjects were enrolled for analyses.The median age was 62.0 years,and 45.6%were male.The educational level of illiteracy or semi-illiteracy,primary,middle and high school or above was 29.8%,45.5%,20.1%,and 3.3%,respectively.Majority of the participants were female,younger,and less educated when compared with nonparticipants.The average body mass index and waist-hip ratios were 24.4±3.4 kg/m^(2) and 0.9±0.1 respectively.Blood sample collection reached a sample size of 1909(479 from subjects with se

关键词： Population Baseline Ophthalmic epidemiology Visual impairment Screening metabonomics

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Liver metabonomics study on the protective effect of glycyrrhetinic acid against realgar-induced liver injury

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Chinese Journal of Natural Medicines 2020年第2期18卷 138-147页

作者： HUO Tao-Guang FANG Ying ZHANG Ying-Hua FENG Cong JIANG Hong Department of Health Laboratory Technology School of Public HealthChina Medical UniversityShenyang 110122China

Glycyrrhetinic acid(GA)is the bioactive ingredient in Glycyrrhizae Radix et Rhizoma.Our previous study has reported that GA has protective effect on realgar-induced hepatotoxicity.However,the details of the hepatoprotective mechanisms of GA on realgar-induced liver injury remain to be elucidated.In the study,mice were divided into control,GA-control,realgar,and co-treated groups.Their liver tissues were used for metabonomics study by ultra-performance liquid chromatography-mass spectrometry(UPLCMS)method.The results illustrate that GA significantly ameliorate the liver injury and metabolic perturbations caused by realgar.Some metabolites,such as phenylalanine,pyroglutamic acid(PGA),proline,carnitine,nicotinamide,choline,lysophosphatidylcholine(LPC)16:0 and LPC 18:2 were found responsible for the hepatoprotective effect of GA.These metabolites are associated with the methylation metabolism of arsenic,cell membrane structure,energy metabolism and oxidative stress.From the results of this study,we infer that the potential hepatoprotective mechanism of GA on realgar-induced liver injury may be associated with reducing arsenic accumulation and its methylation metabolism in the liver,promoting the conjugation of arsenic and GSH to play detoxification effect,and ameliorating the liver metabolic perturbations caused by realgar.

关键词： metabonomics Glycyrrhetinic acid Realgar Liver UPLC-MS

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Study of Serum metabonomics and Formula-Pattern Correspondence in Coronary Heart Disease Patients Diagnosed as Phlegm or Blood Stasis Pattern Based on Ultra Performance Liquid Chromatography Mass Spectrometry

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Chinese Journal of Integrative Medicine 2018年第12期24卷 905-911页

作者： LU Xiao-yan XU Hao ZHAO Tie LI Geng Department of Integrative Cardiology China-Japan Friendship Hospital Cardiovascular Diseases Center Xiyuan HospitalChina Academy of Chinese Medical Sciences

Objectives： To study the characteristics of serum metabonomics in coronary heart disease （CHD） patients diagnosed as phlegm or blood stasis pattern and explore effects of formula-pattern correspondence treatment. Methods： A total of 102 stable CHD patients were enrolled and divided into phlegm group （P group, n=52） and blood stasis group （BS group, n=50） according to pattern identification. Gualou Xiebai Banxia Decoction （瓜萎薤白半夏汤, GXBD） and Xuefu Zhuyu Decoction （血府逐瘀汤, XZD） were used as drug interventions. Relevant indicators of metabonomics were observed by ultra performance liquid chromatography mass spectrometry （UPLC-MS） and pattern recognition. Results： Levels of amino acids and phosphatidylethanolamine （PE） in the CHD group were much higher than those in healthy control group, while the levels of unsaturated fatty acids, sphingosine, Lyso, phosphatidylcholine （PC） were significantly lower （P〈0.01）. Most of the differential metabolites between the CHD and the healthy groups were also common metabolites of phlegm and blood stasis. 7（Z）, 10（Z）- hexadecadienoic acid and DPA were decreased in the P group and increased in the BS group. According to the quantity of retraced metabolites, improvement in metabonomics by formula-pattern correspondence was superior to that without correspondence in the BS group. Based on the varieties of metabolites, GXBD could improve the levels of docosapentaenoic acid （DPA）, sphingomyelin （SM）（d34：1）, and L-Lactic acid and XZD could ameliorate the levels of sphingosine and Vit E in the P group, in the BS group, GXBD could improve vitamin E level and XZD could make improvements in the levels of octadecanoic acid, phosphoglycerol, and SM （d34：1）. Conclusions： Phlegm and blood stasis in CHD patients present specific differential metabolites, and share common metabolites. Remarkable differences have been displayed in pathological properties and severity of phlegm and blood stasis. Patients with phlegm are more likely to have lipid metabolism disorders. However, in patients with blood

关键词： ultra performance liquid chromatography mass spectrometry metabonomics phlegm/stasis pattern in coronary heart disease disease-pattern combination formula-pattern correspondence

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Study on Correspondence between Prescription and Syndrome and the Essence of Phlegm and Blood Stasis Syndrome in Coronary Heart Disease Based on metabonomics

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Chinese Journal of Integrative Medicine 2014年第1期20卷 68-71页

作者：鹿小燕徐浩李耿赵铁 Department of Integrative Cardiology China-Japan Friendship Hospital

Studying the essence of a syndrome has been a key challenge in the field of Chinese medicine.Until now,due to limitations of the methods available,the progress towards understanding such complicated systems has been slow.metabonomics encompasses the dynamics,composition and analysis of metabolites,enabling the observation of changes in the metabolic network of the human body associated with disease.Being from the point of view of the whole organism,metabonomics provides an opportunity to study the essence of a syndrome to an unprecedented level.Phlegm and blood stasis syndrome is the main syndrome associated with coronary heart disease（CHD）,which bring difficulties in clinical treatment due to difficulties associated with differentiation of symptoms and signs.The fundamental differences of material between the two also need to be interpreted.The authors consider that we can use the method of combining a disease（in this case CHD）with associated syndromes（phlegm and blood stasis syndrome）to select patients with phlegm and blood stasis syndrome of CHD,and utilize metabonomics to explore the essence of the syndrome by difference analysis of metabolite spectra.Meanwhile,we can study the syndrome in CM,observe the change regularity of metabolism spectra after the treatment of corresponding and non-corresponding prescription and syndrome,in order to validate the material fundament in the progress of syndrome formation and their differences.This will not only have great significance in enhancing the ability to identify syndrome of phlegm and blood stasis in CHD and to establish the clinical curative criteria,but will also offer a new approach of studying the essence for a syndrome using metabonomics.

关键词： metabonomics phlegm and blood stasis syndrome coronary heart disease combination of disease with syndrome correspondence between prescription and syndrome

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