Objective: To explore the effect of Wamingfen on eosinophil apoptosis and oxygen free radicals and to study the influence of hydrocortisone on airway inflammation in asthma guinea pigs. Methods: Guinea pig models of asthma were induced by egg albumin. The effect of Wamingfen on plasma malonyl dialdehyde (MDA), blood glutathione peroxidase (GSH-Px),erythrocytic superoxide dismutase (SOD) activity , serum hydrocortisone level and the percentage of EOS apoptosis in bronchial-alveolar lavage fluid (BALF) were observed. Results: Wamingfen can apparently increase the content of GSH-Px ,SOD and serum hydrocortisone, promote the apoptosis of EOS and reduce the amount of MDA. Conclusion: Wamingfen can effectively increase serum hydrocortisone content, remove the oxygen free radical, promote eosinophil apoptosis and reduce the hyper-reactivity in the inflammatory airway.

Based on our research team's clinical and basic research results of traditional Chinese medicine (TCM) in the prevention and treatment of ischemic stroke, and combined with TCM syndrome standard manifestations of this disease, wind, phlegm, fire, deficiency and blood stasis, this paper points out definitely that the basic pathogenesis of ischemic stroke is blood stasis caused by deficiency of both Qi and Yin. The pathogenic characteristics are deficiency in origin and excess in superficiality, and the wind, fire, phlegm, deficiency and blood stasis are related one another resulting in this disease; it is established that the basic syndrome types of this disease are deficiency of both Qi and Yin and static blood blocking the collaterals, and the therapeutic regime is a recipe including the TCM ingredients having the actions of nourishing yin, tonifying Qi and improving blood circulation (Yangyin Yiqi Huoxue) and according to the patient's individual variation of syndrome differentiation, the ingredients in the recipe can be added or subtracted. In this report, a new system of treatment for ischemic stroke based on syndrome differentiation is proposed.

Objective To investigate the influence of Guhong injection (GHI) on ATPase activity and inflammatory response after cerebral ischemia/reperfusion (I/R) injury in rats, and evaluate its protective effects on cerebral I/R injury. Methods Seventy-two male Sprague-Dawley (SD) rats were divided into sham group, I/R group, nimodipine group, and the low-dose (2.5 mL/kg, GHI-L), medium-dose (5.0 mL/kg, GHI-M), and high-dose (10.0 mL/kg, GHI-H) of GHI groups according to the random number table method, with 12 rats in each group. The middle cerebral artery occlusion (MCAO) model was established by the intraluminal suture method to prepare the model of focal cerebral ischemia, and reperfusion was performed after 1.5 hours of occluding the middle cerebral artery; the sham group had the same operation process except inserting the nylon thread. The injection of drug in various drug-treated groups was carried out via a tail vein at 0, 12, 24 hours after the onset of reperfusion, while the sham group and I/R group received the same amount of normal saline. At 12 hours after last drug administration, the scores of neurological deficit symptoms were evaluated; the cerebral infarction was observed by triphenyl tetrazolium chloride (TTC) staining; the Na+-K+-ATPase and Ca2+-ATPase activities in the brain tissue were measured by phosphorus determination; the contents of interleukin-6 (IL-6), monocyte chemotactic factor-1 (MCP-1), nitric oxide (NO) in serum were detected by enzyme linked immunosorbent assay (ELISA). Results Compared with the sham group, the neurological function score was significantly decreased, the cerebral infarction was serious, the activities of ATPase was obviously decreased, and the levels of serum inflammatory factors were significantly increased in I/R group. Compared with the I/R group, the neurological function scores were significantly increased in GHI-L group, GHI-M group, GHI-H group and nimodipine group (9.03±0.63, 10.54±2.55, 12.33±1.87, 12.06±1.89 vs. 8.17±1.05, all P < 0.05), the volumes of cerebral infarction were obviously reduced [(18.51±1.80)%, (15.98±1.34)%, (8.61±1.16)%, (8.09±0.96)% vs. (26.52±2.07)%, all P < 0.01], the activities of ATPase were significantly increased [Na+-K+-ATPase (μmol·mg-1·h-1):5.10±0.30, 5.34±0.26, 6.19±0.17, 5.86±0.31 vs. 3.98±0.35, Ca2+-ATPase (μmol·mg-1·h-1): 3.68±0.44, 4.43±0.29, 5.03±0.27, 4.17±0.30 vs. 1.87±0.46, all P < 0.01], and the levels of serum inflammatory factors were decreased obviously [IL-6 (ng/L): 51.61±5.55, 43.88±4.05, 39.71±2.22, 41.28±2.66 vs. 60.11±6.61, MCP-1 (ng/L): 227.82±7.07, 201.58±13.10, 177.23±10.46, 126.80±8.49 vs. 296.01±12.85, NO (μmol/L): 54.48±3.23, 46.84±2.69, 41.15±2.80, 48.62±2.34 vs. 65.25±3.88, all P < 0.05]. Conclusions GHI not only can improve the energy metabolism of brain tissue in a dose-dependent manner, but also inhibit the inflammatory cascade of damage after cerebral I/R in rats, which might be its protective mechanism on cerebral ischemia injury.

Objective To evaluate the safety and efficacy of Yinhua Pinggan granule of Qingjie Xuantou lung defense prescription in the treatment of patients with upper respiratory tract infection accompanied by traditional Chinese medicine (TCM) syndrome of pathogen stagnated in lung-defense phase and to explore the best effective dose.Methods A randomized double blinded, positive drug parallel controlled and multicentric clinical trial was conducted, 270 patients with upper respiratory infection were collected from the First Affiliated Hospital of Zhejiang Chinese Medical University, Affiliated Hospital of Jiangxi Medical University, the Second Affiliated Hospital of Tianjin University of TCM, Tongde Hospital of Zhejiang Province, and Fujian Province Institute of TCM, after screening only 242 cases were consistent with the criteria of enrollment into the Per-Protocol Set (PPS) population, and they were divided into three groups: high dose observation group (82 cases), low dose observation group (79 cases) and control group (81 cases). The high and low dose observation groups were treated with Yinhua Pinggan granule (5 g per bag), high dose means once 1 bag orally taken 3 times a day, low dose indicates once 1 bag taken twice a day; the control group was treated with Yinqiao Jiedu granule (5 g per bag) once 1 bag, 3 times a day; the curative effects of the above groups were all evaluated after consecutive oral administration of the drug respectively for 1 therapeutic course (3 days). The main efficacy evaluation indexes included the TCM syndrome total score and the total score of main symptoms of upper respiratory tract infection; the secondary efficacy evaluation indexes included the situations of patients with different scores of main symptoms of fever and chills, and of disappearance of TCM symptoms; the clinical comprehensive therapeutic effect and the changes of proportion of neutrophils were observed and the safety of drugs was evaluated.Results In PPS population, after treatment the TCM syndrome total score and the total score of main symptoms in the control group and the high and low dose observation groups were all significantly lower than those before treatment, on the 3rd day statistical significant differences were shown (4.4±3.9 vs. 15.5±4.6, 3.7±3.2 vs. 15.0±4.3, 3.0±2.7 vs. 15.2±3.9, 2.8±2.6 vs. 9.7±2.7, 2.3±2.1 vs. 9.5±2.5, 2.0±1.9 vs. 9.6±2.4, respectively, all P < 0.01). After treatment for 1 day, the numbers of patients with 6 score in the control group and the high and low dose observation groups were reduced significantly compared with those before treatment in main symptoms of fever with chills (7 vs. 32 cases, 6 vs. 31 cases, 4 vs. 28 cases, respectively); 3 days after treatment, compared with those before treatment, the numbers of patients with main symptoms of fever with chills score being 0 were significantly increased in the above three groups (65, 73, 77 cases vs. 0 cases, respectively), the numbers of patients with the score being 3 were significantly decreased (16 vs. 47 cases, 5 vs. 46 cases, 5 vs. 52 cases, respectively); the control and high dose observation group had no patients with the score being 6, there was only 1 case with the score being 6 in the low dose observation group. The results showed that the treatments of high and low dose observation groups and the control group all could alleviate the clinical symptoms, and the changes of numbers of patients with the scoresbeing 0 and 3 in high and low dose groups were more significant than those in the control group (respectively 73, 77 vs. 65 cases, 5, 5 vs. 16 cases, allP < 0.05), showing that the antipyretic effect of Yinhua Pinggan granule was superior to that of the Yinqiao Jiedu granule. The disappearance rates of fever with chills symptoms in high and low dose observation groups were significantly higher than that in the control group [respectively 93.9% (77/82), 92.4% (73/79) vs. 80.2% (65/81), allP < 0.05]. The TCM syndrome cure and obvious effect rate and effective rate in high and low dose observation groups were higher than those in the control group [respectively 87.80% (72/82), 79.75% (63/79) vs. 74.07% (60/81) and 98.78% (81/82), 96.20% (76/79) vs. 96.30% (78/81)]; the cure and marked effective rate and effective rate of controlling symptoms of upper respiratory tract infection in high and low dose observation groups were higher than those in the control group [respectively 78.05% (64/82), 74.68% (59/79) vs. 65.43% (78/81) and 98.78% (81/82), 96.20% (76/79) vs. 96.30% (78/81)], comparisons of efficacy among the three groups possessed clinical practical significance, but the differences were not statistically significant (allP > 0.05). The percentages of neutrophils in high and low dose observation groups and control group were significantly lower than those before treatment (respectively 0.61±0.08 vs. 0.63±0.08, 0.62±0.08 vs. 0.64±0.08, 0.61±0.09 vs. 0.64±0.09, allP < 0.05). Yinhua Pinggan granule was safe in the prescribed course of treatment and range of therapeutic dose.Conclusions Yinhua Pinggan granule is a safe and effective drug in the treatment of patients with upper respiratory tract infection accompanied by syndrome of pathogen stagnated in lung-defense phase.

OBJECTIVETo explore permeability of artificial blood-brain barrier (aBBB) by oxygen-glucose deprivation combined (OGD)-induced using tetramethylpyrazine combined with puerarin in vitro.

METHODRats were divided into normal control group, model group, tetramethylpyrazine group, puerarin group, tetramethylpyrazine-puerarin group and nimodipine group. Culture rat brain microvascular endothelial cells and astrocytes in vitro and build the OGD-induced aBBB damage model. Evaluate aBBB damage characteristics by TEER, gamma-GT, AKP and LDH. Determine contents of tetramethylpyrazine, puerarin, nimodipine and calculate drug permeating concentration of OGD-induced aBBB model by HPLC.

RESULTCompared with the model, the level of TEER was lower than the control group with significant difference (P < 0.01). The levels of gamma-GT, AKP in tetramethylpyrazine group, tetramethylpyrazine-puerarin group and nimodipine group were higher than the model group, the differences were significant (P < 0.01). Compared with tetramethylpyrazine group or puerarin group, the level of AKP of tetramethylpyrazine-puerarin group increased significantly (P < 0.01). The differences of levels of TEER, gamma-GT, AKP and LDH between tetramethylpyrazine-puerarin group and nimodipinthe group were significant (P < 0.05). Tetramethylpyrazine-puerarin group has a synergistic effect of increasing TEER, gamma-GT, AKP and reducing LDH. The permeating rate in tetramethylpyrazine-puerarin group was higher than tetramethylpyrazine group and puerarin group.

CONCLUSIONTetramethylpyrazine-puerarin can permeate aBBB more easily and protect aBBB. The cause may relate to reducing the permeability of the OGD-induced aBBB.

Animals ; Blood-Brain Barrier ; drug effects ; Drug Combinations ; Glucose ; physiology ; Isoflavones ; administration & dosage ; pharmacology ; Male ; Oxygen ; physiology ; Permeability ; Pyrazines ; administration & dosage ; pharmacology ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo observe the effects of polydatin on dynamic changes of excitatory amino acids in cerebrospinal fluid and water content of brain tissue of cerebral hemorrhage rats. And to discuss the therapeutic action and mechanisms of polydatin on brain hemorrhagic injured rats.

METHODA quantitative determination method of Asp and Glu was established by microdialysis-HPLC. The cerebral hemorrhage model in rats was induced by local injection of type VII collagenase. The dynamic changes of Asp and Glu in cerebrospinal fluid were observed on 0, 6, 12, 24, 36, 48, 60, 72, 84, 96, 108 h of cerebral hemorrhage rats, and then the water content of brain tissue was detected.

RESULTThe content of Asp and Glu increased rapidly within 24 h after cerebral hemorrhage, and to the highest in 24 h, then decreased gradually. Compared with the cerebral hemorrhage model group, the content of Asp and Glu increased slowly in polydatin group, and there were significant differences in 12-72 h and 6-84 h (P < 0.01, P < 0.05), but there was no significant difference after 84 h and 96 h. Compared with sham group, water content of brain tissue significantly higher in model group, while significantly lower (P < 0.01) in polydatin group.

CONCLUSIONPolydatin can inhibit increasing content of Asp and Glu in cerebrospinal fluid dynamics, and significantly inhibit cerebral edema of cerebral hemorrhage rats. It shows that the mechanisms of anti-cerebral hemorrhage injury of polydatin may be related to increasing of excitatory amino acids after cerebral hemorrhage.

Animals ; Aspartic Acid ; cerebrospinal fluid ; Cerebral Hemorrhage ; cerebrospinal fluid ; drug therapy ; Disease Models, Animal ; Drugs, Chinese Herbal ; therapeutic use ; Excitatory Amino Acids ; cerebrospinal fluid ; Glucosides ; therapeutic use ; Glutamic Acid ; cerebrospinal fluid ; Humans ; Male ; Rats ; Rats, Sprague-Dawley ; Stilbenes ; therapeutic use

OBJECTIVETo study the influence of the different combinations of the main active parts in Yangyintongnao granule on the pharmacokinetics parameters of the two active components--ligustrazine and puerarin using the method of total amount statistic moment for pharmacokinetics.

METHODCombinations were formed according to the dosages of the four active parts (alkaloid, flavone, saponin, naphtha) by orthogonal experiment L9 (3(4)). Blood concentrations of ligustrazine and puerarin were determinated by HPLC at different time. Zero rank moment (AUC) and one rank moment (MRT, mean residence time) of ligustrazine and puerarin have been worked out to calculate the total amount statistic moment parameters was analyzed of Yangyintongnao granule by the method of the total amount statistic moment. The influence of different compatibilities on the pharmacokinetics parameters was analyzed by orthogonal test.

RESULTFlavone has the strongest effect than saponin on the total AUC. Ligustrazine has the strongest effect on the total MRT. Saponin has little effect on the two parameters, but naphtha has more effect on both of them. It indicates that naphtha may promote metabolism of ligustrazine and puerarin in rat.

CONCLUSIONTotal amount statistic moment parameters can be used to guide for compatibilities of TCM.

Animals ; Data Interpretation, Statistical ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; administration & dosage ; pharmacokinetics ; Humans ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; drug therapy

OBJECTIVETo observe the effect of 3'-methoxy puerarin on cerebral infarction volume and free radical change of focal cerebral ischemia-reperfusion injury in rats and discuss the protective effect of 3'-methoxy puerarin on the cerebral ischemic/ reperfusion injury.

METHODThe thread method was used to induce middle cerebral artery embolization, to establish the focal cerebral ischemia-reperfusion model. Rats were divided into five groups: the sham and model group, the two-dose group (5, 10 mg x kg(-1) x d(-1)) of 3'-methoxy puerarin and nimodipine group (5 mg x kg(-1) x d(-1)). The behavior changes and volume of cerebral infarction were observed, and the leves of SOD and the content of MDA were measured.

RESULT3'-methoxy puerarin could significantly improve the symptoms of neurological deficit and reduce the infarct volume, and increased SOD activity and reduced the content of MDA of cortex in cerebral ischemia-reperfusion injury rat, the action of 10 mg x kg(-1) of 3'-methoxy puerarin is more remarkable.

CONCLUSION3'-methoxy puerarin has protective effect on focal cerebral ischemia-reperfusion injury in rat.

Animals ; Brain Ischemia ; drug therapy ; prevention & control ; Disease Models, Animal ; Female ; Humans ; Isoflavones ; pharmacology ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; drug therapy ; prevention & control

OBJECTIVETo study the effect of 3'-methoxy puerarin on cerebral ischemic glutamic acid, aspartic acid, taurine and gamma-aminobutyric acid inhibitory of rats and investigate the protective mechanisms of cerebral ischemia-reperfusion.

METHODUsing middle cerebral artery occlusion rat model, to collect extracellular fluid in rat striatal amino acid neurotransmitters by brain microdialysis and HPLC techniques with fluorescence detection before and after 3'-methoxy puerarin treatment four kinds of amino acids changes.

RESULT3'-methoxy puerarin reduced concentrations of excitatory amino acid (EAA) Asp and Glu, while Tau and GABA inhibitory amino acids were significantly reduced.

CONCLUSION3'-methoxy puerarin reduce ischemia-induced brain EAA toxicity against EAA neurotoxicity, regulate the brain neurotransmitter amino acid content, improve the excitatory and inhibitory amino acid balance is one of the mechanisms that to improve and protect the important acute cerebral infarction in rat brain nuclei.

Animals ; Brain Ischemia ; drug therapy ; metabolism ; Excitatory Amino Acids ; metabolism ; Female ; Isoflavones ; therapeutic use ; Male ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; drug therapy ; metabolism

Ischemic stroke(IS)is a multifactorial and heterogeneous disease.Despite years of studies,effective strategies for the diagnosis,management and treatment of stroke are still lacking in clinical practice.Metabolomics is a growing field in systems biology.It is starting to show promise in the identification of biomarkers and in the use of pharmacometabolomics to help patients with certain disorders choose their course of treatment.The development of metabolomics has enabled further and more biological appli-cations.Particularly,metabolomics is increasingly being used to diagnose diseases,discover new drug targets,elucidate mechanisms,and monitor therapeutic outcomes and its potential effect on precision medicine.In this review,we reviewed some recent advances in the study of metabolomics as well as how metabolomics might be used to identify novel biomarkers and understand the mechanisms of IS.Then,the use of metabolomics approaches to investigate the molecular processes and active ingredients of Chinese herbal formulations with anti-IS capabilities is summarized.We finally summarized recent developments in single cell metabolomics for exploring the metabolic profiles of single cells.Although the field is relatively young,the development of single cell metabolomics promises to provide a powerful tool for unraveling the pathogenesis of IS.