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L-theanine has been shown to have a therapeutic effect on depression.However,whether L-theanine has an excellent preventive effect on depression in children and adolescents and what its mechanism is have not been well explained.Given the complexity of the pathogenesis of depression,this study investigated the preventive effect and mechanism of L-theanine on depression in juvenile rats by combining serum and hippocampal metabolomic strategies.Behavioral tests,hippocampal tissue sections,and serum and hippocampal biochemical indexes were studied,and the results confirmed the preventive effect of L-theanine.Untargeted reversed-phase liquid chromatography-quadrupole-time-of-flight mass spec-trometry and targeted hydrophilic interaction liquid chromatography-triple quadrupole mass spec-trometry were developed to analyze the metabolism changes in the serum and hippocampus to screen for potential biomarkers related to L-theanine treatment.The results suggested that 28 abnormal me-tabolites in the serum and hippocampus that were considered as potential biomarkers returned to near-normal levels after L-theanine administration.These biomarkers were involved in various metabolic pathways,mainly including amino acid metabolism and lipid metabolism.The levels of amino acids and neurotransmitters in the phenylalanine,tryptophan,and glutamic acid pathways were significantly reduced after L-theanine administration compared with chronic unpredictable mild stress-induced rats.In summary,L-theanine had a significant preventive effect on depression and achieved its preventive results on depression by regulating various aspects of the body,such as amino acids,lipids,and inflammation.This research systematically analyzed the mechanism of L-theanine in preventing depression and laid the foundation for applying L-theanine to prevent depression in children and adolescents.
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Viscum coloratum (Kom.) Nakai is a well-known medicinal plant. However, the optimal harvest time for V. coloratum is unknown. Few studies were performed to analyze compound variation during storage and to improve post-harvest quality control. Our study aimed to comprehensively evaluate the quality of V. coloratum in different growth stages, and determine the dynamic variation of metabolites. Ultra-performance liquid chromatography tandem mass spectrometry was used to quantify 29 compounds in V. coloratum harvested in six growth periods, and the associated biosynthetic pathways were explored. The accumulation of different types of compounds were analyzed based on their synthesis pathways. Grey relational analysis was used to evaluate the quality of V. coloratum across different months. The compound variation during storage was analyzed by a high-temperature high-humidity accelerated test. The results showed that the quality of V. coloratum was the hightest in March, followed by November, and became the lowest in July. During storage, compounds in downstream steps of the biosynthesis pathway were first degraded to produce the upstream compounds and some low-molecular-weight organic acids, leading to an increase followed by a decrease in the content of some compounds, and resulted in a large gap during the degradation time course among different compounds. Due to the rapid rate and large degree of degradation, five compounds were tentatively designated as "early warning components" for quality control. This report provides reference for better understanding the biosynthesis and degradation of metabolites in V. coloratum and lays a theoretical foundation for rational application of V. coloratum and better quality control of V. coloratum during storage.
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Viscum/chemistry , Plants, Medicinal/chemistry , Chromatography, Liquid , Mass Spectrometry , MetabolomicsABSTRACT
OBJECTIVE To s tudy the impr ovement effects of tilianin on the atherosclerosis （AS）model mice and its potential mechanism. METHODS Eight C 57BL/6J mice were taken as the normal group. Forty ApoE－/－ mice were randomly divided into model group ，tilianin low-dose ，medium-dose and high-dose groups [ 2.1，3.5，7.0 mg/（kg·d）] and simvastatin group [positive control drug ，3.5 mg/（kg·d）]，with 8 mice in each group. Normal group was given normal diet ，and other groups were given high-lipid diet to induce AS model. At the same time ，normal group and model group were given normal saline intragastrically ， administration groups were given relevant drug intragastrically ，once a day ，for 12 consecutive weeks. The levels of TC ，TG， LDL-C，HDL-C，Ox-LDL，IL-1β，IL-6，MCP-1 and TNF-α in plasma were determined. The pathomorphological changes of the aorta in mice were observed. The positive rate of ICAM- 1，VCAM-1 and PCNA in the aorta were determined. mRNA expressions of MMP- 2，MMP-9，TGF-β1，Smad2 and Smad 3 as well as protein expressions of TGF-β1，Smad2/3 and p-Smad 2/3 were also determined in aorta of mice. RESULTS Compared with normal group ，the plasma levels of TC ，TG，LDL-C，Ox-LDL，IL-1β， IL-6，MCP-1 and TNF-α in model group were increased significantly（P＜0.01），while HDL-C level was significantly reduced （P＜0.01）. Lipid plaques were formed in the aorta ，and the plaque area was large and caused severe stenosis of the lumen. mRNA expressions of MMP- 2，MMP-9，TGF-β1，Smad2 and Smad 3 as well as positive rate of ICAM- 1，VCAM-1，PCNA and protein expression TGF-β1，Smad2/3，and p-Smad 2/3 in the aorta were significantly increased （P＜0.01）. Compared with model group ， most of above indexes of medication groups were improved significantly （P＜0.05 or P＜0.01）. CONCLUSIONS Tilianin can inhibit the activation of TGF-β1/Smads signaling pathway and then inhibit the proliferation of vascular smooth muscle cells ，reduce ， inflammation and regulate lipid metabolism to inhibit the No.81960766） formation of AS.
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OBJECTIVE：To s tudy the effects of Dracocephalum moldavica total flavonoids （TFDM）on AMPK/SIRT 1/PGC-1α signaling pathway ，and to explore the mechanism of its protective effect on myocardial ischemia reperfusion injury （MIRI）rats. METHODS：Totally 50 healthy male SD rats were randomly divided into sham operation group ，model group ，TFDM group [ 60 mg/（kg·d），by extract] ，Compound C+TFDM group [ig administration of 60 mg/（kg·d）TFDM+intravenous injection of 250 μg/kg Compound C（AMPK inhibitor ）via tail vein 15 min before reperfusion] ，EX-527+TFDM group [ig administration of 60 mg/ （kg·d）TFDM+ip injection of 5 mg/kg EX- 527（SIRT1 inhibitor）20 min before reperfusion] ，with 10 rats in each group. They were given relevant medicine intragastrically ，once a day ，for consecutive 7 days. After last ig administration ，sham operation group underwent sham operation ，other 4 groups were established MIRI model by ligating left anterior descending coronary artery ， ischemia for 30 min and reperfusion for 2 h. After reperfusion ，the myocardial histopathological changes were observed by HE staining；RP-HPLC method was used to determine the contents of ATP ，ADP，AMP and NAD + in cardiac tissue. mRNA expressions of AMPK ，SIRT1 and PGC- 1α were detected by quantitative real-time PCR assay. Western blotting assay was the expressions of SIRT 1 and PGC- 1α protein in myocardium. RESULTS： Compared with sham operation group ， model group showed myocardial fib ers arranged disorder and horizontal stripes disappearance ，cell swelling burst and necrosis ，and nuclei deformation displacement ；the contents of ATP and NAD+，mRNA expression of AMPK ，SIRT1 and PGC- 1α，protein expression of SIRT 1 and PGC- 1α in cardiac tissue were decreased significantly （P＜0.05 or P＜0.01）；the contents of ADP and AMP ，the phosphorylation level of AMPK protein were increased significantly （P＜0.01）. Compared with model group ，myocardial pathological morphology were improved significantly in TFDM group ；the contents of ATP and NAD + in cardiac tissue ，mRNA expression of AMPK ，SIRT1 and PGC- 1α，the phosphorylation level of AMPK protein ，the protein expression of SIRT 1 and PGC- 1α were increased significantly（P＜0.05 or P＜ 0.01），while the contents of ADP and AMP were decreased significantly （P＜0.01）. Compared with TFDM group ，improvement effects of Compound C + TFDM group and EX- 527 + TFDM group on above indexes were reversed （P＜0.05 or P＜0.01）. CONCLUSIONS：TFDM may play a protective role on myocardium by activating AMPK/SIRT 1/PGC-1α signaling pathway and regulating energy metabolism.
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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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To ensure the safety of the commercially available chenpi, a convenient and fast analytical method was developed for the determination of 133 pesticide residues in chenpi using gas chromatography-tandem mass spectrometry (GC-MS/MS). In this study, different extraction solvents, redissolution solvents and adsorbents were tested according to the recovery and purification effect to obtain a modified QuEChERS method. The samples were extracted with acetonitrile. During the clean-up step, octadecyl-modified silica (C18) and graphitized carbon black (GCB) were selected, and aminopropyl (NH2) was used instead of primary secondary amine (PSA) because of its weaker ion exchange capacity which had little effect on the recovery of ditalimfos. Samples were quantified by matrix-matched calibration with internal stan-dards. All pesticides showed good linearity in the respective range, both with values of r2 >0.99. The average recoveries of the pesticides spiked samples ranged from 70.0％ to 112.2％ with the RSDs of 0.2％–14.4％. The modified QuEChERS method was validated and applied to twenty real samples. Five pesticides were found in eight batches, but no pesticide exceeded the maximum residue limits (MRL, MRL reference to European commission).
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Notoginseng Radix et Rhizoma has the efficacy of dissolving stasis and hemostasis and reducing swelling and easing pain. Panax notoginseng saponins (PNS) is the main active component of Notoginseng Radix et Rhizoma, and the main components include ginsenoside Rb1, Rg1, Re, Rd and notoginsenoside R1. Injections with PNS as the medicinal material basis have become main TCM injections for the treatment of cerebral vascular diseases, with confirmed clinical efficacy. This article reviewed the research progress in pharmacological effects, clinical application and adverse reactions of PNS in treatment of cerebral vascular disease, with a purpose to provide references for further research and clinical application.
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A sensitive and selective method based on gas chromatography hyphenated to mass spectrometry (GC-MS) was developed and validated for the determination of atractylon in rat plasma. Plasma samples were processed by liquid-liquid extraction with ethyl acetate-n-hexane (1:1, v/v) using acetophenone as an internal standard (IS). Analytes were determined in selective ion monitoring (SIM) mode using target ions at m/z 108.1 for atractylon and m/z 105.1 for acetophenone. The calibration curve was linear over the concentration range of 10-1000 ng/mL with lower limit of quantification of 10 ng/mL. The intra- and inter-day precision variations were not more than 10.4% and 9.6%, respectively, whilst accuracy values ranged from -6.5% to 4.9%. Extraction recovery of the assay was satisfactory. This method was suc-cessfully applied to quantification and pharmacokinetic study of atractylon in rat plasma after in-tragastric administration of Atractylodis extract.
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Objective To summarize the clinical manifestations,pathological character,diagnosis and treatment of aggressive angiomyxoma (AAM).Methods A computer-based online search of PubMed database and CHKD database was undertaken for literature about AAM published from all the relevant documents with the key words of aggressive angiomyxon.According to the condition 210 articles were analyzed.All the articles were analyzed about natural history,clinical manifestation,diagnosis,pathological character,treatment and prognosis of AAM.Results A total of 282 cases in well-documented articles had been reported,among which 64 were male and 218 were female,with male to female ratio of 1:3.4.The age of the patients from 1 to 83 years(mean 40.38 years).The most common sites were the perineum,genital tract and soft tissue in pelvic cavity in females and the scrotum,spermatic cord and groin in males.None of the cases could be accurately diagnosed as AAM preoperatively.The minimum diameter of the tumors was 1 cm,and the maximum was 60 cm.All the specimens showed typical pathological features of AAM as reported previously.Immunohistochemistry indicated that AAM tended to be strongly positive for vimentin,CD34,Desmin,estrogen receptor,progesterone receptor but mostly negative for S-100 and Ki-67 and Actin.The medical history was from 1 month to 20 years.The recurrence of the postoperative follow-up was 2 months to 20 years.The diagnosis depended on pathological examination.Conclusions AAM is a sort of unusual soft connective tissue tumor.It is a kind of unknown cause,slow progression,locally invasive,easy to recur after tumor resection.Long-term follow-up is quite necessary because of the high rate of local recurrence.
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Sanqi is a popular traditional Chinese medicine and commonly used for promoting blood circulation and removing blood stasis. Notoginsenoside R1, ginsenoside Rg1, Re, Rb1 and Rd are the major active constituents of Sanqi. The purpose of the study was to investigate the pharmacokinetic behavior of the five active constituents from total saponin from Sanqi when it was used in the blood stasis animals or in combination with Gegen. The concentrations of the five active constituents in rat plasma were determined by an ultra-HPLC-ESI-MS/MS method. The main pharmacokinetic parameters were calculated and statistically analyzed using the unpaired student's t-test. It was found that the pharmacokinetic parameters of notoginsenoside R1, ginsenoside Rg1 and Rb1 represented a statistically significant difference (Po0.05) between the normal rats and the blood stasis rats after administration of total saponin from Sanqi (TSFS). And there were statistically significant differences (Po0.05) in the pharmacokinetic parameters of all the five constituents between administration of TSFS alone and combined with total flavonoid from Gegen (TFFG) in blood stasis rats. It suggested that the pharmacokinetic behavior of the active constituents from TSFS could be changed when it was used in blood stasis animals or in combination with TFFG.
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A high-performance liquid chromatography coupled ultraviolet （HPLC-UV） method was developed for a chemical fingerprint analysis of Viscum coloratura. Eighteen peaks were selected as the common peaks and Homoeriodictyol-7-O-β-D-apiosiyl-（1→2）-β-D-glucoside was used as a reference. The relative areas of common peaks were used for hierarchical clustering analysis and similarity calculation. Thirty-seven samples collected from different sources were classified into five groups. The similarities of 21 batches Viscum coloratura samples were beyond 0.90. The results obtained suggest that the chromatographic fingerprint can efficiently identify Viscum coloratum. Additionally, the fingerprints can then be used to evaluate the correlation between Viscum coloratura and hosts.
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A high-performance liquid chromatography coupled ultraviolet (HPLC-UV) method was developed for a chemical fingerprint analysis ofViscum coloratum. Eighteen peaks were selected as the common peaks and Homoeriodictyol-7-O-β-D-apiosiyl-(1→2)-β-D-glucoside was used as a reference.The relative areas of common peaks were used for hierarchical clustering analysis and similarity calculation.Thirty-seven samples collected from different sources were classified imo five groups.The similarities of 21 batches Viscum coloratuma samples were beyond 0.90.The results obtained suggest that the chromatographic fingerprint can efficiently identify Viscum coloratum.Additionally,the fingerprints can then be used to evaluate the correlation between Viscum coloratum and hosts.
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Objective: To compare the pharmacodynamic action of Radix Notoginseng after fermented by different strains bioconversion.Methods:The models of cerebral ischemia and hypoxia were established,thrombosis in vivo were induced by collagen-Adr,ventricular fibrillation of mice by chloroform,and perfusion experiment of the ex vivo heart of cavia cobaya was used.Results:100,200mg/kg doses of all samples had protective effects on ischemia and hypoxia mice,1# sample can inhibit thrombosis induced by collagen-adrenaline obviously after intraperitoneal injection in dosage of 200mg?kg-1?d-1 for 5days.All groups significantly reduced the incidents of ventricullar fibrillation induced by chloroform in mice except 100mg/kg dose of 1#,furthermore,compared with control high dose group(5#),the incidents of high dose groups of 3、4# deceased significantly.All samples had the effect of dilating coronary artery,but there effects on myocardial contractile force and cardiac preload were different.Conclusion:The primary cardiovascular related pharmacological researches demonstrated the vary action changes of 1-4# samples compared with the sample 5#.This result has revealed that the chemical structure of Radix Notoginseng transformed and that is coincide with initial analysis of phytochemical analysis.
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OBJECTIVE: To establish an HPLC method for simultaneous determination of peoniflorin,calycosin and ferulic acid in Kangmin granules.METHODS: The separation was performed on a Kromasil C18 column (250 mm?4.6 mm,5 ?m),and the mobile phase consisted of methanol-acetonitrile-0.4% phosphonic acid (20 ∶ 10 ∶ 70) with flow rate of 1.0 mL?min-1.The detection was performed at wavelength of 254 nm.Column temperature was room temperature and the injection volume was 10 ?L.RESULTS: The linear ranges of peoniflorin,calycosin and ferulic acid were 180～3 600 ?g?mL-1(r=0.999 2),4.6～92.0 ?g?mL-1(r=0.999 1) and 8.0～160.0 ?g?mL-1(r=0.999 4),respectively.The average recoveries were 98.3%(RSD=1.8%,n=9),99.0% (RSD=2.0%,n=9) and 100.5%(RSD=1.1%,n=9),respectively.CONCLUSION: The method is simple,accurate,sensitive and reproducible for the quality control of Kangmin granules.
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AIM: To establish the fingerprint chromatogram of Dangguijisheng Injection (Radix Angelicae Sinensis, Herba Visci) METHODS: HPLC with Zorbax SB-C 18 ( 4.6mm? 250mm,5-Micro) column was used, A phase (mechanol∶tetrahydrofuran=85∶15) and B phase ( 0.5% acetic acid (gradient elution)) were adopted as a mobile phase, respectively, and detection wavelength set at 270 nm. RESULTS: 18 peaks constitued the HPLC fingerprint of Compound Dangguijisheng Injection. CONCLUSION:The method is simple and accurate with a good reproducibility and can be used as a quality control for Dangguijisheng Injection.