Mechanism of Banxia Baizhu Tianma decoction to prevent the development of prehypertension and excessive phlegm-dampness syndrome in rats based on metabonomics technology / 药学学报

The alterations of serum biological endogenous chemicals in rats with phlegm dampness accumulation syndrome of prehypertension (PHT) were interfered by Banxia Baizhu Tianma decoction (BBT), and the metabolic regulatory pathway of BBT was clarified using serum metabonomics analysis. To replicate the rat model of prehypertension phlegm dampness syndrome, blood pressure, behavioral markers, and serum biochemical markers of rats were collected. BBT's effectiveness in controlling blood pressure and blood lipids was assessed, and changes in endogenous small molecules in rat serum were determined using UPLC-Q-Orbitrap MS metabolic analysis. The results showed that BBT could regulate 9 metabolites, including arachidonic acid, cholic acid, glycodeoxycholic acid, N-adenosyltyrosine, arginine, lysophosphatidylethanolamine (20:0/0:00), lysophospholipid (P-18:0), lysophospholipid (18:0), lysophospholipid (22:5(7Z,10Z,13Z,16Z,19Z)). MetaboAnalyst was used to analyze the metabolic pathway. There were 7 metabolic pathways closely related to the change of blood pressure in rats, among which arachidonic acid metabolic pathway was the most critical. The metabolism difference foreign body in the model rats tends to return to the normal level, which provides a research basis for the mechanism of BBT from the perspective of metabonomics. This study was approved by the Experimental Animal Welfare Ethics Review Committee of Shandong University of Traditional Chinese Medicine (approval number: SDUTCM20211103001).

Underlying Mechanisms of Bile Acids in Progression of Hypertension Based on Metabolomics and Network Analysis / 中国实验方剂学杂志

ObjectiveTo explore the underlying mechanism of bile acids and metabolites as well as the key metabolic pathways and important endogenous targets in prehypertension. MethodThe metabolic mechanism of prehypertension was explored with non-targeted metabolomics combined with network analysis. The serum metabolomics of patients with prehypertension was analyzed by ultra-high performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry. The relevant biological functions and signal targets were predicted and generated by network analysis. Finally，the predicted targets of this important pathway were verified by in vitro experiments，and the relevant information was verified by enzyme-linked immunosorbent assay （ELISA） and Western blot. ResultAs revealed by non-targeted metabolomics，there were 64 potential biomarkers and 13 metabolic pathways in the normal group，the prehypertension group， and the hypertension group. The results of network analysis and biological verification showed that the occurrence of prehypertension was related to vascular inflammation caused by the abnormal metabolism of bile acids and aromatic amino acids. Bile acid metabolism plays an important role in the occurrence and development of prehypertension by regulating the vascular inflammatory response. Amino acid N-acyltransferase，myeloperoxidase， and bile acid downstream receptor TGR5 are critical in the changes of the metabolic network. ConclusionIn prehypertension，bile acids are presumedly involved in regulating vascular inflammation， resulting in damage to blood vessels in prehypertension.

Effects of isorhyncophylline on hippocampal metabolism using 1H NMR-based metabolomics combined with molecular docking analysis / 药学学报

The purpose of this study was to investigate the effect of isorhyncophylline on hippocampal endogenous metabolites in spontaneously hypertensive rats (SHR) by 1H NMR metabolomics and molecular docking. Twelve SHR were randomly divided into a model group and a treatment group. Six Wistar-Kyoto rats were selected as a control group. The rats in the treatment group were administered isorhyncophylline (0.3 mg·kg-1) while the rats in the other two groups were treated with the same amount of sterilized saline solution. Animal experiment was authorized by the Ethics Committee of Shandong University of Traditional Chinese Medicine (No. SDUTCM20210721002). Hippocampal tissues were removed after administration for 8 weeks and assayed by 1H NMR based metabolomics technology combined with a pattern recognition method to find characteristic metabolites, and the metabolic targets were retrieved from the Kyoto Encyclopedia of Genes and Genomes database. Molecular docking technology was used to evaluate binding of isorhyncophylline to the core targets. The results of a principal components analysis (PCA) and partial least squares discriminant analysis (PLS-DA) showed a clear cluster of samples among three groups. There were seven differentially altered metabolites, and glucose metabolism and glutamate metabolism were the principal related pathways. Molecular docking indicated that isorhyncophylline had good binding properties with nine key candidate target proteins. According to the above research results, isorhyncophylline can influence energy metabolism and glutamate metabolism in the hippocampus.

The molecular mechanism by which the circadian rhythm regulates body metabolism and research progress on intervention in the circadian rhythm by traditional Chinese medicine / 药学学报

Circadian rhythm is an internal regulatory mechanism that allows organisms to adapt to circadian changes in the external environment, and can regulate the body's steady state by affecting the metabolic pathways of multiple organs. When exogenous factors such as eating time, worktime changes, and sleep disturbances cause the body's circadian rhythm to be disrupted, the risk of developing metabolic syndrome is significantly increased. This article explores the relationship between circadian rhythm and body metabolism and summarizes the molecular mechanisms by which circadian rhythm regulates the digestive system, liver and bile acid production, and kidney function. We review research progress on intervention in the circadian rhythm by traditional Chinese medicine and provide a reasonable and valuable basis for follow-up studies on the role of traditional Chinese medicine in research on the molecular mechanisms of regulation of circadian rhythm.

Review of chemical constituents, pharmacological effects and clinical applications of Jiaotai Pills and predictive analysis of its quality marker(Q-marker) / 中国中药杂志

Jiaotai Pills is a traditional medical prescription to treat the incompatibility of heart and kidney. It has the distinctive functions of heart and kidney communication, sedation and hypnosis, anti-anxiety and depression, as well as the improvement of insulin resistance. However, this pill is broadly used to cure insomnia, anxiety, depression, and diabetes in the contemporary clinical trials. Based on the article, it illustrates the research progress of the chemical ingredients, pharmacological actions, and clinical applications of Jiaotai Pills. With respect to the "five principles" of Q-marker in Chinese medicine, the Q-marker of Jiaotai Pills is comprehensively predicted and analyzed, noting that berberine, epiberberine, coptisine chloride, palmatine chloride, berberine chloride, berberrubine chloride, ferulic acid, cinnamic acid, cinnamaldehyde, proanthocyanidin B2 can be treated as the Q-marker of Jiaotai Pills. In addition, these components of Q-marker have been selected as indicators to provide a significant reference for the quality control and surveillance research of Jiaotai Pills.

A new polyacetylene and a new isonicotinic acid glucoside from Bidens parviflora Willd． / 药学学报

The ethyl acetate fraction of 80% ethanol extract from Bidens parviflora Willd．was isolated and purified by silica, polyamide, Sephadex LH-20 and HPLC. A total of eleven compounds were isolated and identified by physicochemical properties and spectral data as (2S)-11E-tetradecene-3,5,7,9-tetrayne-1,2,13-triol (1), pyridine-4-formyl-O-β-D-glucopyranoside (2), maritimein (3), trichocarpine (4), okanin-4-methyl ether-3′-O-β-D-glucopyranoside (5), okanin-4-methyl ether-4′-O-β-D-(6″-acetyl)-glucopyranoside (6), (Z)-6-O-(4″-acetyl-6″-O-p-coumaroyl-β-D-glucopyranosyl)-6,7,3′,4′-tetrahydroxyaurone (7), quercetin-3-O-α-L-arabinoside (8), hyperoside (9), (3S)-(6E,12E)-tetradecadiene-8,10-diyne-1,14-diol-3-O-β-D-glucopyranoside (10), bipinnata polyacetyloside B (11). Compounds 1 and 2 are new compounds, compounds 4 and 8 were isolated from the genus Bidens for the first time, compounds 5-7, 10 and 11 were isolated from this plant for the first time.

Qualitative Analysis on Perilla frutescens Leaves and Stalks by UPLC-Q-Exactive-Orbitrap-MS / 中国实验方剂学杂志

Objective:To establish a method for qualitative analysis of components in Perilla frutescens leaves and stalks by liquid chromatography-mass spectrometry (LC-MS)，so as to explore the substance basis of pharmacodynamics differences between P.frutescens leaves and stalks.Method:P. frutescens leaves and stalks were extracted by 80% methanol-water ultrasound. The samples were analyzed by UPLC-Q-Exactive-Orbitrap-MS comprehensively. Halo-C18 column (2.1 mm×100 mm，2.7 μm) was used for gradient elution with 0.05% formic acid aqueous-0.05% acetonitrile formate as mobile phase in positive and negative ion modes. The flow rate was 0.3 mL·min-1，the column temperature was 40 ℃，and the injection volume was 5 μL.Result:The chemical compound in P. frutescens was deduced and identified based on the retention time of chromatography，and the exact molecular weight，excimer ion peaks，fragment ions and reference materials in Xcalibur software. The chemical composition of P. frutescens was identified by Mass Frontier 7.0 software. Totally 4 amino acids，7 phenylpropanoids，10 flavonoids，12 triterpenoids，7 organic acids，4 fatty acids，10 unknown compounds and 54 compounds were identified. Among them，6 triterpene acids, including glochidone, were identified in P. frutescens for the first time. The structures of five characteristic compounds were analyzed. There were 45 constituents in P.frutescens leaves and 32 constituents in P. frutescens stalks. They had 23 common constituents.Conclusion:LC-MS can identify the components of P. frutescens rapidly and effectively. This study provides an important theoretical basis for the quality control of different parts of P. frutescens and the development and utilization of P. frutescens.

Effect of Chaenomelis Fructus Alcohol Extract on Arthritis Inflammation and Apoptosis of Synovial Cells in Rheumatoid Arthritis Model / 中国实验方剂学杂志

Objective:To study the protective effect and mechanism of Chaenomelis Fructus alcohol extract (CFE) on the synovium of rheumatoid arthritis (RA). Method:Sixty male SD rats were randomly divided into normal group and model group. RA model was made by injection of complete Freund's adjuvant， and then was randomly divided into model group， CFE low， medium and high dose group and Tripterygium glycoside group according to the inflammatory score. The CFE groups (0.15，0.30，0.60 g·kg-1·d-1) had intragastric administration once a day for 30 d after the model establishment. The blank control group and the model group were given the same volume saline water by gavage. After all the drugs were given， the blood， joint tissues and synovium tissue of rats were collected. The levels of interleukin-1β (IL-1β)， interleukin-6 (IL-6)， interleukin-10 (IL-10) and tumor necrosis factor (TNF)-α in serum were detected by enzyme linked immunosorbent assay (ELISA)， the pathological changes of synovium were observed by hematoxylin eosin (HE) staining， and the expressions of B-cell lymphoma-2 (Bcl-2)，Bcl-2 associated X protein (Bax) and death factor (Fas) in joints were detected by Western blot. Result:Compared with normal group， the swelling degree and inflammation index of rats' feet in model group increased significantly， the levels of inflammatory factors IL-1β， IL-6， TNF-α in serum increased (P<0.01)， anti-inflammatory factor IL-10 decreased (P<0.01)， the protein expression of Bax， Fas and Bcl-2 increased， and the statistical results of Bcl-2 showed significant difference (P<0.05). Compared with model group， the swelling degree and inflammatory index of the plantar of RA rats were improved in the middle and high dose groups of CFE (P<0.01)， the pathological changes such as synovial tissue hyperplasia and inflammatory cell infiltration were reduced in each dose group， and the levels of IL-1β， IL-6 and TNF-α in serum were reduced (P<0.05)， anti inflammatory factor IL-10 increased (P<0.05)， the disorder of inflammatory cytokine in the model was corrected， Bax， Fas expression increased， Bcl-2 protein expression decreased (P<0.01). Conclusion:CFE can reduce the degree of inflammation in RA joint and has obvious anti RA effects， which may be related to the apoptosis of synoviocytes induced by CFE.

Lipidomics study on intervention by Uncaria on hepatic metabolic disorder in spontaneously hypertensive rats / 药学学报

In this paper, the lipidomics was used to analyze the changes to address how Uncaria interrupts lipid metabolism in the liver of spontaneously hypertensive rats, and to explore the mechanism of action of Uncaria. All the experiments were approved by the animal protection and use committee of Shandong University of Traditional Chinese Medicine. UHPLC-Q Extractive orbitrap high-resolution mass spectrometry was used to collect lipid metabolite information of the rat livers. Through pattern recognition, matters with noticeable differences were recognized. Mass spectrum and data base searching helped to identify the potential biomarkers. Pattern recognition results indicated that the rats from control versus SHR group showed clear differences. Compared with the rats from the control group, there are decreases in sphosphatidylcholine, phosphatidic acid, diacylglycerol and sphingomyelin in rats from the SHR group, however lysophosphatidylcholine, triglyceride, linoleic acid, arachidonic acid and ceramide are increased. Uncaria could regulate the disorder of lipid metabolism by interfering with glycerophospholipid, sphingolipid, linoleic acid, and arachidonic acid metabolic pathways. This study provided the mechanistic understanding of the impact of Uncaria on lipid metabolism and revealed the lipid metabolism pathways affected to offer the explanation for the complex mechanism of action.

Study on the Intervention Effects of Pinggan Prescription () on Spontaneously Hypertensive Rats Based on Metabonomic and Pharmacodynamic Methods / 中国结合医学杂志

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.

Structural characterization of Glehniae Radix polysaccharides using partial acid hydrolysis-hydrophilic interaction liquid chromatography-mass spectrometry / 中国中药杂志

Water-soluble polysaccharides from traditional Chinese medicine have properties of complex structure and high molecular, resulting in hardly complete their structural characterization.However, a "bottom-up" approach could solve this problem.Glehniae Radix extract was extracted with hot water and then precipitated by 40% ethanol to obtain Glehniae Radix polysaccharides (RGP). Subsequently, a partial acid hydrolysis method was carried out and the effects of acid concentration, time and temperature on hydrolysis were investigated. Under the optimum hydrolysis condition (1.5 mol•L⁻¹ trifluoroacetic acid, 4 h, and 80 ℃), RGP were hydrolyzed to characteristic oligosaccharide fragments. Futher, a hydrophilic liquid chromatography- mass spectrometry method was used for the separation and structural characterization of the polysaccharide hydrolysates. According to MS and MS/MS analysis of several standard disaccharides, a method for determining the type of polysaccharide glycosidic linkage by mass spectrometry was established. The results showed that the polysaccharide hydrolysates were linear glucan containing 1, 4-glycosidic bonds. And gluco-oligosaccharides with the degrees of polymerization (DP) of 4-11 were obtained after partial acid hydrolysis.

Action mechanism of Mahuang Xixin Fuzi decoction for mice with influenza based on metabolomics information / 中国中药杂志

This study aimed to analyze the endogenous metabolite changes in the serum of mice infected with H1N1 virus after intervention by Mahuang-Xixin-Fuzi decoction (MXF) based on metabolomics method, investigate potential biomarkers and related metabolic pathways, and explore the therapeutic mechanism of MXF through metabolomics technology. Thirty-six Kunming (KM) mice were randomly divided into three groups: normal group, model group and MXF group. Influenza virus H1N1 was used by nasal drip to establish influenza mice model. The mice in MXF group were orally administrated with MXF for 6 consecutive days after inoculation, and the other two groups were given with equal volume of saline solution in the same way. Body weight, rectal temperature, morbidity and mortality were recorded daily. Serum samples were collected 24 hours after the last administration for HPLC-TOF-MS analysis. The results showed that as compared with the normal group, the body weight and rectal temperature were decreased in model group, and their lung index and mortality rate were significantly increased (P<0.05); MXF had good therapeutic effects on the abnormity of body weight, rectal temperature, lung index and high mortality rate of mice infected with H1N1 virus. The original data collected from the serum samples were analyzed with R language, MPP, SIMCA-P and other software, and significant changes were found in 14 kinds of endogenous substances from mice serum (P<0.05). As compared with model group, the potential metabolic markers in MXF group recovered to normal levels to a certain degree after being intervened by MXF. Further analysis with MetPA data platform showed that, the pathways involved in 14 metabolites included glucose metabolism, arachidonic acid metabolism, glycerophospholipids and sphingolipids metabolism etc. The metabolomics study and pharmacological experiment showed that MXF might play a role of efficacy by improving glucose metabolism, regulating arachidonic acid metabolism, glycerophospholipid and sphingolipid metabolic pathways.

Formula Optimization in Renshen Jianxin Capsule Based on Uniform Design and Anti-myocardial Ischemia Effect / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To realize quadratic formula optimization of Renshen Jianxin Capsule (RJC) by screening Chinese herbs with major anti-myocardial ischemia effect in RJC and optimize their optimal dosages.</p><p><b>METHODS</b>By following "uniform design-pharmacodynamic experiment-mathematical modeling-formula optimization", authors employed U10(10(8)) uniform design in the experiment. Eight Chinese herbs contained in RJC were taken as observatory factors. Electrocardiograph (ECG) changes of myocardial ischemia induced by isoproterenol were taken as pharmacodynamic indices. The mathematical model between herbal factors and pharmacodynamic indices was established using stepwise regression analysis to screen Chinese herbs with major anti-myocardial ischemia effect. Their optimal dosages were optimized using the grid algorithm.</p><p><b>RESULTS</b>The regression equation was y =1. 7889 -0. 3247 Ginseng xSalvia Miltiorrhiza -0. 0663 Astragalus membranaceus xOriental Waterplantain tuber. Forecasting factors included were Ginseng, Salvia Miltiorrhiza, Astragalus membranaceus, and Oriental Waterplantain tuber. The optimal formula dosage calculated by the grid algorithm was Ginseng 1. 62 g, Astragalus membranaceus 4. 62 g, Salvia Miltiorrhiza 2. 43 g, and Oriental Waterplantain tuber 1. 66 g.</p><p><b>CONCLUSION</b>Uniform design combined with stepwise regression analysis and grid algorithm were able to realize quadratic formula optimization of RJC.</p>

The mechanism of action of valsartan studied by HPLC-TOF/MS / 药学学报

High performance liquid chromatography-time-off-flight mass spectrometer (HPLC-TOFMS) technology coupled with partial least squares discriminant analysis (PLS-DA) processed by SIMCA-P software was applied to investigate serum endogenous metabolites alternations of valsartan in spontaneous hypertension rats (SHR). And MetPA platform was used to connect identified potential biomarkers in corresponding metabolic pathways to find possible therapeutic mechanism of valsartan. Valsartan significantly declined the blood pressure of SHRs (P < 0.05) at fourth week. The metabolic profiling significantly changed and four metabolites involved in G protein-coupled pathway were identified. Metabolomics is able to detect holistic and microcosmic alternations in organism, so as to elucidate therapeutic mechanism of drugs.

Optimization for compatibility of Ramulus Uncariae cum Uncie total alkaloids and Semen Raphani total alkaloids based on partial least-squares regression analysis / 中草药

Objective: To explore the research method suitable for the component compatibility and optimization design of Chinese materia medica (CMM) by taking the blood pressure-lowering effect of the effective components in Ramulus Uncariae cum Uncie total alkaloids (RUCUTA) and Semen Raphani total alkaloids (SRTA) as the research objects. Methods: According to the procedure of "orthogonal design-evaluation on drug effect-partial least-squares regression (PLSR)", using contractive pressure as index, the ratio of RUCUTA and SRTA was optimized by orthogonal design method. The data were analyzed by range analysis, variance analysis, multiple regression analysis, and PLSR analysis. Results: According to the result of the data analysis and considering the economic costs, the optimal ratio of the two components was 25 μg/g RUCUTA and 30 μg/g SRTA. Conclusion: The compatibility of RUCUTA and SRTA could effectively reduce blood pressure. The orthogonal design method combined with PLSR could eliminate the interaction among the various factors and be suitable for the component compatibility in CMM and optimization design.

Urine metabonomic study on hypertension patients of ascendant hyperactivity of gan yang syndrome by high performance liquid chromatography coupled with time of flight mass spectrometry / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the changes of urine metabolites in hypertension patients of ascendant hyperactivity of Gan yang syndrome (AHGYS), and to explore its essence in hypertension patients.</p><p><b>METHODS</b>Ten typical hypertension patients of AHGYS were recruited as the patient group, and the other twelve healthy volunteers were recruited as the normal group. The metabolite profiling in the urine were collected using by high performance liquid chromatography coupled with time of flight mass spectrometry (HPLC-TOFMS). The principal component analysis (PCA) and partial least-square discriminant analysis (PLS-DA) were analyzed using SIMCA-P Software. The differential metabolites in the urine were found out and identified. The possible relevant metabolic pathways were explained.</p><p><b>RESULTS</b>The data from the analysis by PCA in the urine samples of the patient group and the normal group showed, two sets of data could be obviously classified in the score plot. Compared with the normal group, significant changes happened to the body metabolism in the patient group. The metabolites relevant to hypertension patients of AHGYS were determined using the PLS-DA. Fifteen compounds of the structure and metabolic pathways had been confirmed through inquiring KEGG Database, mainly including amino acids, free fatty acids, sphingosine, and so on.</p><p><b>CONCLUSIONS</b>The hypertension patients of AHGYS were studied using HPLC-TOFMS combined with pattern recognition, thus finding out small molecular metabolic markers from the microscopic field, which was advantageous in probing the biological nature of Chinese medicine syndromes.</p>

The epidemiological study of work-related musculoskeletal disorders and related factors among automobile assembly workers / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the work-related musculoskeletal disorders among automobile assembly workers, to discusses the related risk factors and their relationship.</p><p><b>METHOD</b>The selected 1508 automobile assembly workers from a north car manufacturing company were regarded as the study object. The hazard zone jobs checklist, Nordic musculoskeletal symptom questionnaire (NMQ) and pain questionnaire were used to perform the epidemiological cross-sectional and retrospective survey and study for the General status, awkward ergonomics factors and related influencing factors, and musculoskeletal disorders of workers.</p><p><b>RESULTS</b>The predominant body sites of occurring WMSDs among automobile assembly workers were mainly low back, wrist, neck and shoulders, the predominant workshop section of occurring WMSDs were mostly concentrated in engine compartment, interior ornament, door cover, chassis and debugging section. The predominant body site of WMSDs among engine compartment and chassis section workers was low back, interior ornament workers were low back and wrist, door cover workers was wrist, chassis workers was low back, debugging workers were neck and low back. Neck musculoskeletal disorders had the trend with the increase of a body height; Smoking may increase the occurrence of musculoskeletal disorders.</p><p><b>CONCLUSION</b>The WMSDs appears to be a serious ergonomic proble assem among automobile assembly workers, predominant occurring site of WMSDs is with different workshop section, its characteristics is quite obvious, probably related to its existing awkward work position or activities. The worker height and smoking habits may be important factors which affect musculoskeletal disorders happen.</p>