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Systemic lupus erythematosus (SLE) is an autoimmune disease with multiple organ involvement. There are still many limitations and individual differences in the treatment based on glucocorticoids and immunosuppressants. In recent years, more and more studies have shown that the combination of traditional Chinese medicine in the treatment of SLE has the advantages of good efficacy, low adverse reactions, and high safety. However, the exact regulatory mechanism and combined traditional Chinese medicine in the treatment of SLE are still unclear. This paper reviews the research on the mechanism of traditional Chinese medicine in the treatment of SLE from metabonomic, immune cells, lymphocyte factors and apoptosis, etc, provides ideas for exploring the mechanism of traditional Chinese medicine in the treatment of SLE with modern methods.
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KangFuXinYe (KFX), the ethanol extract of the dried whole body of Periplaneta americana, is a well-known important Chinese medicine preparation that has been used to treat digestive diseases such as gastric ulcers for many years in China. However, its therapeutic effect and mechanism are not yet well understood. Thus, the aim of this study was to investigate the gastro-protective effects of KangFuXinYe (KFX) in indomethacin-induced gastric damage. Rats were randomly divided into six groups as follows: control, treated with indomethacin (35 mg·kg), different dosages of KFX (2.57, 5.14 and 10.28 mL·kg, respectively) plus indomethacin, and sucralfate (1.71 mL·kg) plus indomethacin. After treatment, rat serum, stomach and gastric homogenates were collected for biochemical tests and examination of histopathology firstly. Rat serum was further used for metabolomics analysis to research possible mechanisms. Our results showed that KFX treatment alleviated indomethacin-induced histopathologic damage in rat gastric mucosa. Meanwhile, its treatment significantly increased cyclooxygenase-1 (COX-1), prostaglandin E (PGE) and epidermal growth factor (EGF) levels in rat serum and gastric mucosa. Moreover, KFX decreased cyclooxygenase-2 (COX-2) and interleukin-6 (IL-6) levels. Nine metabolites were identified which intensities significantly changed in gastric damage rats, including 5-hydroxyindoleacetic acid, indoxylsulfuric acid, indolelactic acid, 4-hydroxyindole, pantothenic acid, isobutyryl carnitine, 3-methyl-2-oxovaleric acid, sphingosine 1-phosphate, and indometacin. These metabolic deviations came to closer to normal levels after KFX intervention. The results indicate that KFX (10.28 mL·kg) exerts protective effects on indomethacin-induced gastric damage by possible mechanisms of action (regulating tryptophan metabolism, protecting the mitochondria, and adjusting lipid metabolism, and reducing excessive indomethacin).
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A metabonomic approach involving an ultrahigh-performance liquid chromatography combined with Fourier transform ion cyclotron resonance mass spectrometry (UHPLC-FT-ICR-MS) was used to investi-gate the changes in the endogenous metabolites in the plasma of rats with yeast-induced pyrexia treated with Gegenqinlian decoction (GQLD), aspirin and itraconazole. The differences in the small molecule profiles of treatment using traditional Chinese medicine, etiological treatment and symptomatic treat-ment were elucidated. Thirty-six plasma metabolites were identified or putatively identified, and the effects of the three medicines on the thirty-six metabolites were studied. Their metabolic pathways indicated that GQLD, aspirin and itraconazole ameliorated the rats with yeast-induced pyrexia pre-dominantly by regulating the metabolisms of phospholipid, sphingolipid, fatty acid oxidation, fatty acid amides, amino acid and glycerolipid in vivo. The pharmacodynamics and metabonomic results showed that the three medicines exhibited the therapeutic effects on pyrexia by regulating the perturbations of multiple metabolisms. The study provided a scientific basis for an in-depth understanding of the ther-apeutic effects of GQLD, aspirin and itraconazole on rats with yeast-induced pyrexia.
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OBJECTIVE@#To investigate the effects of Pinggan Prescription (, PGP) on hypertension by the associated methods of metabonomic and pharmacodynamic.@*METHODS@#A total of 32 male spontaneously hypertensive rats (SHRs) were randomly divided into two groups by using the random number table method: a treatment group (n=18) and a model group (n=14). The Wistar rats (n=14) were used as the normal group. Different prescription were used to intervene three groups: the treatment group in which PGP extract was administered orally at a dose of 18.336 g/kg (PGP/body weight), and the model group in which physiological saline was administered at the equivalent dose. The same treatment was applied to the normal group as the model group. The blood pressure was measured by tail-cuff method, and pharmacodynamic indexes including cyclic adenosine monophosphate (cAMP) and angiotensin II (Ang II) were tested by enzyme-linked immunosorbent assay. The plasma samples from three groups were detected by gas chromatography-mass spectrometry (GC-MS).@*RESULTS@#Compared with the model group, blood pressure of treatment group was obviously reduced after continuous curing with PGP (P<0.01). The pharmacodynamic results illustrated that the content of Ang II increased with the raised blood pressure and the cAMP expressed the converse trend. After curing with PGP, the content of Ang II decreased, the difference between model group and treatment group was significant (P<0.01), and the cAMP expressed the converse trend. Five potential biomarkers were identified, including arachidonic acid, hexadecanoic acid, elaidic acid, octadecanedioic acid and 9,12-octadecadienoic acid. These metabolites had shown significantly changes as followed: arachidonic acid, hexadecanoic acid and elaidic acid were significantly higher and octadecanedioic acid and 9,12-octadecadienoic acid were lowered in the model group than those in the normal group. After the treatment of PGP, the metabolites had the trends of returning to normal along with the reduced blood pressure.@*CONCLUSIONS@#PGP intervention for hypertension played a major role in the metabolism of arachidonic acid and linoleic acid. Metabonomic with pharmacodynamic methods could be potentially powerful tools to investigate the mechanism of Chinese medicine.
Subject(s)
Animals , Male , Biomarkers , Blood , Discriminant Analysis , Drugs, Chinese Herbal , Pharmacology , Gas Chromatography-Mass Spectrometry , Hypertension , Blood , Drug Therapy , Least-Squares Analysis , Metabolic Networks and Pathways , Metabolomics , Models, Biological , Principal Component Analysis , Rats, Inbred SHR , Rats, WistarABSTRACT
Abstract Kudouzi (Sophora alopecuroides L., Fabaceae) is an effective folk medicine, but it always causes a hepatic and renal toxicity in clinical therapy. The toxic mechanism remains unclear. This paper detected the urinary and plasma metabolites alteration by 1H NMR-based metabonomics study in Kudouzi-induced rats to evaluate the toxic mechanism for clinical security. The male Sprague-Dawley rats were orally dosed with 0.5 and 1 g Kudouzi/kg weight once per day for consecutive 14 days. Urine samples were collected at day −1 (before treatment), and days 7, 14, and 21 for NMR analysis, respectively. Plasma samples were harvested at day 14 for NMR and biochemical analysis. The metabonomic profiling of Kudouzi-treated rats differed from that of the vehicle. This was confirmed by the biochemistry analysis. The accumulated subacute toxicity of Kudouzi was visible with dosing time, and persisted at day 21 even after the disposal was ended. The observable biochemical pathways alterations included inhibited TCA cycle, activated anaerobic glycolysis, perturbed amino acids metabolism, and disordered gut microbiota. The results evidenced the toxicity mechanism of Kudouzi from a systematic and holistic view.
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OBJECTIVE: To investigate the therapeutic effects metabolic mechanism of Schisandra chinensis polysaccharide (SCP) on chronic fatigue syndrome (CFS). METHODS: CFS rat model was established in a variety of ways such as the bondage, excessive exercise, crowded and noise environment. The Morris water maze test, the open-field test and the tail-suspension test were performed to evaluate the CFS model. The gas chromatography-mass spectrometry (GC-MS) method was conducted to screen the different metabolites in rat urine and analyze the metabolic pathway. RESULTS: The body weight of rats were increased and their space exploration and memory ability were strengthened after SCP supplement. The eleven diversity urine metabolites were detected and the involved metabolic pathways were the tricarboxylic acid cycle and the alanine, aspartic and glutamic acid metabolic pathways. CONCLUSION: SCP could relieve the chronic fatigue syndrome. The metabolic mechanism is relative to the improvement of SCP on the tricarboxylic acid cycle and the alanine, aspartic and glutamic acid metabolic pathways.
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OBJECTIVE: To develop an intergrated urinary metabonomic strategy based on RP-UPLC-MS and HILIC-UPLC-MS method and to investigated the mechanism of osteoporosis and the prevention effect of glucocorticoid osteoporosis of Gushudan. METHODS: The RP-UPLC-MS and HILIC-UPLC-MS method were developed for rat urine metabolite profiling study among control group, model group and Gushudan treatment group. Principal component analysis (PCA) were used to find the biomarkers, further more, to explore the mechanism of the prevention effect on glucocorticoid osteoporosis of Gushudan. RESULTS: In the mode of RP-UPLC-MS, low polarity metabolites like phenylacetylglycine, N2-succinic acid-L-ornithine were found while relatively high polarity metabolites like betaine, hypoxanthine were found in the mode of HILIC-UPLC-MS. And twenty-two potential biomarkers have been totaly found in the urine of glucocorticoid osteoporosis, primiarily related to amino acid metabolism, energy metabolism, lipid metabolism, intestinal flora metabolism and kidney damage. Gushudan has intervention effects on rats with osteoprosis via the regulation of multiplemetabolic pathways. CONCLUSION: The combination of RP-UPLC-MS and HILIC-UPLC-MS method can give a more comprehensive profiling of endogenous metabolites and it also indicates metabonomic strategy has become a powerful tool to evaluate the overall efficacy of traditional Chinese medicine (TCM) and to calrify the mechanism of TCM.
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Objective To analyze the different metabolites of the classical activated (M1) ,alternatively activated (M2) and resting BV2 cells by metabolomics method .Methods The mRNAs of several potential biomarkers were determined by real-time PCR analyses to confirm the state of BV2 cells .Static GC-MS combined with metabolomics technology was used to analyze the metabolic changes .Results There were 15 biomarkers identified between the M1 group and the resting group ,and 15 biomarkers were found in the M2 group and the resting group .Conclusion The present study provides an effective way to reveal the mechanism of the polarization of BV 2 cell ,and it might provide a theoretical basis to prevent or treat the neurodegen-erative diseases .
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OBJECTIVE: To analysis the regulation of biomarkers by an metabonomic investigation of chronic unpredictable mild stress (CUMS) rats. To provide a clue for elucidate the mechanism of depression. METHODS: CUMS induced rat animal depression model, the behavioral changes of rats were observed; meanwhile, hippocampus samples were obtained and subjected to GC-MS analysis to find potential biomarkers of depression. RESULTS: Body weight, sucrose intake in the sucrose preference, ambulationn number and rearing number in open-field test of the CUMS rats decreased significantly after 21 d compared with those of the control groups. Metabonomics analysis showed that the model group separated the control group from T1. Ten potential biomarkers are identified from the loading plot between control and model group. CONCLUSION: Ten biomarkers are identified among the detected compounds. These Results suggest that the depressed state may be associated with perturbation of amino acid metabolism, energy metabolism and lipid metabolism.
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Objective:To apply 'HNMR spectroscopic analysis and principal components analysis(PCA) for investigating the fluctuation of metabolites between hydrocortisone-induced kidney deficiency syndrome(Shenxu Zheng) rats and the normal rats. Methods: Using 'HNMR based metabolic profiling and PCA, we investigated the difference of urine metabolites between the normal rats and rats with hydrocortisone-induced kidney deficiency syndrome. We also explained the changes of the related metabolic pathway or metabolic network. Results: The changes following hydrocortisone intervention of rats could be identified by PCA,and the kidney deficiency syndrome rats entered a state of "hyperfunction",involving a series of changes in metabolic pathway and metabolic network. The response integral area of lactic acid(δ 1. 37) increased, indicating the accumulation of metabolites of lactic acid. The amount of dimethylamine(δ 2. 72) also increased, indicating that the disorder of kidney function was related to kidney-deficiency syndrome. The response of creatinine(δ 3. 87) ,asparaginic acid(δ 2.83) ,taurine(δ 3.44,3. 28), and hippurate( 7.84,7. 56,7. 64,3. 97) all decreased significantly,indicating that the hydrocortisone might cause adrenal cortex excretion injury. The response integral area of succinate( 2. 41) and citric acid( 2. 53,2. 68) decreased, which was usually caused by disorder of the mitochondrial function. Conclusion: It is suggested that the metabonomic approach can be used to investigate the pathophysiological changes under certain physiopathologic conditions. This study provides evidence for understanding "Shenxu Zheng"(kidney deficiency syndrome) in traditional Chinese medicine and for diagnosis and therapy of such diseases.