[Research progress of ion channels relating to cerebral ischemic diseases and prevention and treatment with traditional Chinese medicine].

Cerebral ischemia is a series of clinical symptoms and signs of cerebral ischemia, hypoxia and neuronal damage caused by cerebral artery stenosis or occlusion due to atherosclerosis or thrombosis, which seriously affects human health and quality of life. Cerebral ischemia involves the cascade reaction of the "neurovascular unit" system, and finally affects the normal physiological function of nerve cells and produces a series of pathological changes. And the changes in the structure and function of various ion channels in the cell membrane play an important role during this process. This article illustrates the changes in the ion channel associated with ce-rebral ischemic diseases, such as the potassium ion channels, sodium ion channels, calcium channels and other relevant channels, like AQP, TRPM2, TRPM7, TRPV4, ASICs, Cl~- channel, and explores the intervention effect of traditional Chinese medicine in prevention and treatment of cerebral ischemic diseases from the perspective of ion channels, in order to provide references for potential targets involving in drug development for the future prevention and treatment of cerebral ischemic diseases.

[Effect of baicalin on inflammatory response and TLR4/NF-κB signaling pathway of human brain microvascular endothelial cell after hypoxia-reoxygenation injury].

In this study, the oxygen-glucose deprivation(OGD) model in the human brain microvascular endothelial cell(HBMEC) was used to simulate the ischemic neuronal damage and observe the inflammatory response, explore the possible mechanisms for treating cerebral ischemia/reperfusion and improving memory impairment from the view point of inhibiting inflammatory response, which is of great reference significance for related Chinese medicine treatment of ischemic diseases. HBMECs were given with drugs at the same time of OGD injury, and reoxygenated for 2 h after 4 h treatment. Cell supernatant was then collected, and the inflammatory factors in cell supernatant were detected. Immunofluorescence assay was used to detect HBMECs morphology and expression of p-nuclear factor kappa-light-chain-enhancer of activated B(p-NF-κB); Western blot was used to detect expression changes of Toll like receptor 4(TLR4), myeloid differentiation primary response 88(MYD88) and p-NF-κB. The results showed that, after OGD modeling, the levels of interleukin 6(IL-6), IL-1α, IL-1ß and tumor necrosis factor-α(TNF-α) were significantly increased; baicalin protected HBMEC, inhibited intranuclear transcription of p-NF-κB, significantly decreased HBMEC release of inflammatory factors caused by OGD injury, and inhibited the expression of TLR4, MYD88, and p-NF-κB. The studies suggested that baicalin had obvious protective effect on HBMECs damaged by OGD, and could inhibit inflammatory response. Its protection mechanism may be related to inhibiting TLR4 signaling pathways.

Chinese medicine shenfu injection for heart failure: a systematic review and meta-analysis.

Objective. Heart failure (HF) is a global public health problem. Early literature studies manifested that Shenfu injection (SFI) is one of the most commonly used traditional Chinese patent medicine for HF in China. This article intended to systematically evaluate the efficacy and safety of SFI for HF. Methods. An extensive search was performed within 6 English and Chinese electronic database up to November 2011. Ninety-nine randomized controlled trails (RCTs) were collected, irrespective of languages. Two authors extracted data and assessed the trial quality independently. RevMan 5.0.2 was used for data analysis. Results. Compared with routine treatment and/or device support, SFI combined with routine treatment and/or device support showed better effect on clinical effect rate, mortality, heart rate, NT-proBNP and 6-minute walk distance. Results in ultrasonic cardiography also showed that SFI combined with routine treatment improved heart function of HF patients. There were no significant difference in blood pressure between SFI and routine treatment groups. Adverse events were reported in thirteen trails with thirteen specific symptoms, while no serious adverse effect was reported. Conclusion. SFI appear to be effective for treating HF. However, further rigorously designed RCTs are warranted because of insufficient methodological rigor in the majority of included trials.

Mechanism of salvianolic acid B protecting H9C2 from OGD/R injury based on mitochondrial fission and fusion / 药学学报

This study aims to investigate the effect of salvianolic acid B (Sal B), the active ingredient of Salvia miltiorrhiza, on H9C2 cardiomyocytes injured by oxygen and glucose deprivation/reperfusion (OGD/R) through regulating mitochondrial fission and fusion. The process of myocardial ischemia-reperfusion injury was simulated by establishing OGD/R model. The cell proliferation and cytotoxicity detection kit (cell counting kit-8, CCK-8) was used to detect cell viability; the kit method was used to detect intracellular reactive oxygen species (ROS), total glutathione (t-GSH), nitric oxide (NO) content, protein expression levels of mitochondrial fission and fusion, apoptosis-related detection by Western blot. Mitochondrial permeability transition pore (MPTP) detection kit and Hoechst 33342 fluorescence was used to observe the opening level of MPTP, and molecular docking technology was used to determine the molecular target of Sal B. The results showed that relative to control group, OGD/R injury reduced cell viability, increased the content of ROS, decreased the content of t-GSH and NO. Furthermore, OGD/R injury increased the protein expression levels of dynamin-related protein 1 (Drp1), mitofusions 2 (Mfn2), Bcl-2 associated X protein (Bax) and cysteinyl aspartate specific proteinase 3 (caspase 3), and decreased the protein expression levels of Mfn1, increased MPTP opening level. Compared with the OGD/R group, it was observed that Sal B had a protective effect at concentrations ranging from 6.25 to 100 μmol·L-1. Sal B decreased the content of ROS, increased the content of t-GSH and NO, and Western blot showed that Sal B decreased the protein expression levels of Drp1, Mfn2, Bax and caspase 3, increased the protein expression level of Mfn1, and decreased the opening level of MPTP. In summary, Sal B may inhibit the opening of MPTP, reduce cell apoptosis and reduce OGD/R damage in H9C2 cells by regulating the balance of oxidation and anti-oxidation, mitochondrial fission and fusion, thereby providing a scientific basis for the use of Sal B in the treatment of myocardial ischemia reperfusion injury.

Repair and regeneration of myocardial fibroblasts after myocardial injury and regulation by traditional Chinese medicine / 中国药理学通报

Cardiomyocytes are highly differentiated terminal cells with poor self-renewal ability. Therefore, after myocardial infarction necrotic cardiomyocytes cannot be effectively replenished, and the infarcted area is quickly replaced by fibrous tissue, which seriously affects cardiac function. The reduction of the number of myocardial cells and the destruction of the structural integrity of the heart have caused cardiovascular diseases such as myocardial infarction and heart failure, which continue to endanger human life and health. At present, the treatment of coronary heart disease has made great progress. The commonly used treatment options for myocardial repair after myocardial infarction mainly include stem cell transplantation, exosome mediation and microenvironment construction, but all of them are difficult to solve to varying degrees. Cardiac fibroblasts occupy the majority of cardiac cells, and the distribution characteristics of fibroblasts and their role in the process of myocardial infarction make them important effector cells after myocardial infarction. Therefore, this article reviews the source, distribution, post-infarction status of myocardial fibroblasts and the effect of fibroblasts on cardiomyocytes, in order to provide new treatment ideas and solutions for fibroblasts in the repair and regeneration of myocardial cells after myocardial infarction.

Optimization of extraction process of Chuanxiong Rhizoma-Gastrodiae Rhizoma based on network pharmacology and multi-index orthogonal test / 中国中药杂志

To optimize the extraction process of Chuanxiong Rhizoma-Gastrodiae Rhizoma herb pair by network pharmacology combined with analytic hierarchy process(AHP)-entropy weight method and multi-index orthogonal test. The potential active components and targets of Chuanxiong Rhizoma-Gastrodiae Rhizoma were screened by network pharmacology and molecular docking, and the process evaluation indexes were determined with reference to the Chinese Pharmacopoeia(2020 edition). The core components of Chuanxiong Rhizoma-Gastrodiae Rhizoma were determined as gastrodin, parishin B, parishin C, parishin E, ferulic acid, and 3-butylphthalide. With the extraction volume of each indicator and yield of dry extract as comprehensive evaluation indicators, the extraction conditions were optimized by the AHP-entropy weight method and orthogonal test as the ethanol volume of 50%, the solid-liquid ratio of 1∶8(g·mL~(-1)), extraction for three times, and 1.5 h each time. Through network pharmacology and molecular docking, the process evaluation index was determined, and the optimized process was stable and reproducible for the extraction of Chuanxiong Rhizoma-Gastrodiae Rhizoma herb pair, which could provide reference for in-depth research.

Effect of asiaticoside on OGD/R induced injury of H9C2 cardiomyocytes based on PI3K/Akt/Beclin-1 signaling pathway / 药学学报

In order to investigate the effects of asiaticoside (Ass) on H9C2 cardiomyocytes, the present study examined the potential intervention of Ass on the proliferation and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/Bcl-2 homology domain protein (Beclin-1) signaling pathway in H9C2 cardiomyocytes following oxygen and glucose deprivation/reperfusion (OGD/R) injury. H9C2 cardiomyocytes were selected as the research objects, and the activity of H9C2 was detected by cell counting kit-8 (CCK-8). H9C2 cells were divided into control group, OGD/R group, Ass low concentration group (10 μmol·L-1), Ass high concentration group (80 μmol·L-1) and Ass high concentration + chloroquine group (80 μmol·L-1 + 50 μmol·L-1). The control group was cultured under normal conditions, and the other groups were treated with oxygen and glucose deprivation for 4 h and reperfusion for 2 h. The activity and content of aspartic aminotransferase (AST), lactate dehydrogenase (LDH) and creatine kinase (CK) in the supernatant of H9C2 cardiomyocytes were detected by enzyme-linked immunosorbent assay. Autophagy staining assay kit with monodansylcadaverine (MDC) method to observe cellular autophagy; molecular docking technique to identify the molecular targets of Ass. Immunofluorescence was used to observe the effect of the drug on cell number. The expression levels of PI3K, Akt, selective autophagy adaptor protein (P62) and Beclin-1 were detected by Western blot. Compared with OGD/R group, Ass group had a protective effect from 10-80 μmol·L-1, and the activities and contents of AST, LDH and CK were decreased. The protein expression levels of PI3K, Akt, P62 and Beclin-1 were decreased. Compared with the administration group, the activities and contents of AST, LDH and CK in Ass high-concentration + chloroquine group were significantly decreased, and the protein expression levels of PI3K, Akt, Beclin-1 and P62 were significantly decreased. Immunofluorescence showed that the inhibitor group and each administration group had different degrees of protective effect compared with the model group. Asiaticoside can reduce the injury of H9C2 cardiomyocyte induced by OGD/R, reduce the content of AST, LDH and CK, reduce the expression level of P62 protein, and reduce autophagy, which may be closely related to the inhibition of PI3K/Akt/Beclin-1 signaling pathway activation.

Baicalin improves inflammatory response of human microglia by regulating cAMP-PKA-NF-κB/CREB pathway / 中国中药杂志

This study aims to investigate the effects of baicalein(BAI) on lipopolysaccharide(LPS)-induced human microglial clone 3(HMC3) cells, with a focus on suppressing inflammatory responses and elucidating the potential mechanism underlying the therapeutic effects of BAI on ischemic stroke via modulating the cAMP-PKA-NF-κB/CREB pathway. The findings have significant implications for the application of traditional Chinese medicine in treating cerebral ischemic diseases. First, the safe dosage of BAI was screened, and then an inflammation model was established with HMC3 cells by induction with LPS for 24 h. The cells were assigned into a control group, a model group, and high-, medium-, and low-dose(5, 2.5, and 1.25 μmol·L~(-1), respectively) BAI groups. The levels of superoxide dismutase(SOD) and malondialdehyde(MDA) in cell extracts, as well as the levels of interleukin-1β(IL-1β), IL-6, tumor necrosis factor-α(TNF-α), and cyclic adenosine monophosphate(cAMP) in the cell supernatant, were measured. Western blot was performed to determine the expression of protein kinase A(PKA), phosphorylated cAMP-response element binding protein(p-CREB), and nuclear factor-kappa B p65(NF-κB p65). Hoechst 33342/PI staining was employed to assess cell apoptosis. High and low doses of BAI were used for treatment in the research on the mechanism. The results revealed that BAI at the concentrations of 10 μmol·L~(-1) and below had no impact on normally cultured HMC3 cells. LPS induction at 200 ng·mL~(-1) for 24 h reduced the SOD activity and increased the MDA content in HMC3 cells. However, 5, 2.5, and 1.25 μmol·L~(-1) BAI significantly increased the SOD activity and 5 μmol·L~(-1) BAI significantly decreased the MDA content. In addition, BAI ameliorated the M1 polarization of HMC3 cells induced by LPS, as indicated by cellular morphology. The results of ELISA demonstrated that BAI significantly lowered the levels of TNF-α, IL-1β, IL-6, and cAMP in the cell supernatant. Western blot revealed that BAI up-regulated the protein levels of PKA and p-CREB while down-regulating the expression of NF-κB p65. Hoechst 33342/PI staining results indicated that BAI mitigated the apoptosis of HMC3 cells. Overall, the results indicated that BAI had protective effects on the HMC3 cells induced by LPS, and could inhi-bit inflammatory response and improve cell apoptosis, which might be related to the regulation of the cAMP-PKA-NF-κB/CREB pathway.

The coronary heart disease of phlegm-stasis cementation syndrome in mini-swine based on platelet proteomics / 药学学报

Based on the technology of platelet proteomics, the key regulatory proteins and pathogenesis of coronary heart disease with phlegm and blood stasis syndrome were explored and analyzed. Based on the previous laboratory research, the model of coronary heart disease in mini-swine with phlegm-stasis cementation syndrome was duplicated. The model was judged by the changes in blood lipid and myocardial tissue characteristics. Furthermore, the platelet proteins were studied by quantitative proteomics, and the differentially expressed proteins were screened. The critical regulatory proteins and biological pathways of coronary heart disease with phlegm-stasis cementation syndrome were analyzed by bioinformatics. After ten weeks of modeling, the levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), very low density lipoprotein (VLDL-C), triglyceride (TG), creatine kinase (CK) and creatine kinase-MB (CK-MB) in the model group were significantly increased, reflecting the pathological changes such as increased blood lipid, abnormal coagulation function and myocardial ischemia in the model group. In addition, compared with the sham group, there were 26 up-regulated proteins and 8 down-regulated proteins in the platelets of the model group. Combined with bioinformatics analysis, it was found that differential proteins mainly involved in glycolysis/gluconeogenesis, pyruvate metabolism, lipid and atherosclerosis, Ras protein signal transduction. Among them, lactate dehydrogenase B (LDHB), alcohol dehydrogenase 5 (ADH5), neuroblastoma ratsarcoma viral oncogene homolog (NRAS) and Kirsten ratsarcoma viral oncogene homolog (KRAS) play a central role when interacting with other proteins and simultaneously participate in multiple action pathways. The results showed that LDHB, ADH5, NRAS, and KRAS may be the marker proteins in CHD with phlegm-stasis cementation syndrome by regulating glycolysis/gluconeogenesis, pyruvate metabolism, lipid and atherosclerosis, Ras protein signal transduction and other biological processes.

Proteomics reveals the protective mechanism of salvianolate injection on early hyperacute myocardial infarction / 药学学报

The hyperacute stage of myocardial infarction refers to a period of time within 30 minutes after the occurrence of myocardial infarction, when the symptoms are not obvious and the diagnosis is difficult, and the related pathophysiological mechanism has received less attention. In this study, proteomics was used to investigate the pathological changes in the early hyperacute phase of myocardial infarction, aiming to provide experimental evidence for pathological mechanism of myocardial infarction hyperacute stage. Meanwhile, the intervention effect and related mechanism of salvianolate injection were discussed based on heat shock protein B6 (HSPB6), aiming to benefit the clinical rational use of salvianolate injection. The protein expression changes before and after myocardial infarction model establishment were detected by label-free proteomics via mass spectrometry and analyzed by bioinformatics method. Then the binding effect of salvianolate injection on the commonly differential protein HSPB6 was evaluated by molecular docking technology, which was finally verified by animal experiments. All animal experimental protocols were approved by the Ethics Committee of Xiyuan Hosptial (2022XLC041). The results of this study showed that a total of 2 166 proteins were quantified by lable-free proteomics, of which 194 shared differential proteins were involved in myocardial injury and body regulation in the hyperacute phase of myocardial infarction, mainly involving molecular functions such as protein homodimerization activity, oxygen binding and transport, and serine endopeptidase inhibitor activity. Among them, HSPB6 protein is involved in the regulation of myocardial function. Molecular docking results indicated that magnesium salvianolate acetate, which is the main component of salvianolate injection, had the lowest binding energy with HSPB6 protein: -14.53 kcal·mol-1. Animal experiments showed that compared with the Sham group, the model group had significantly lower ejection fraction (EF) and fractional shortening (FS) (P < 0.001), cardiac blood perfusion decreased significantly (P < 0.001). There were obvious pathological changes such as myocardial fiber disorder, cardiomyocyte edema and interstitial small blood vessel congestion; the injury of cardiac function of rats in the administration group was attenuated, and the FS of rats in the low-dose group was significantly improved (P < 0.05), the pathological injury of myocardial tissue was markedly mitigated, and the expression of HSPB6 protein was up-regulated to varying degrees (P < 0.01, P < 0.001). In conclusion, salvianolate injection could be able to improve the cardiac function and pathological morphology of rats in the early hyperacute stage of myocardial infarction, and its mechanism may be related to the promotion of expression of HSPB6.

Huoxin Pill Reduces Myocardial Ischemia Reperfusion Injury in Rats via TLR4/NFκB/NLRP3 Signaling Pathway / 中国结合医学杂志

OBJECTIVE@#To explore the protective effect of Huoxin Pill (HXP) on acute myocardial ischemia-reperfusion (MIRI) injury in rats.@*METHODS@#Seventy-five adult SD rats were divided into the sham-operated group, model group, positive drug group (diltiazem hydrochloride, DH), high dose group (24 mg/kg, HXP-H) and low dose group (12 mg/kg, HXP-L) of Huoxin Pill (n=15 for every group) according to the complete randomization method. After 1 week of intragastric administration, the left anterior descending coronary artery of the rat's heart was ligated for 45 min and reperfused for 3 h. Serum was separated and the levels of creatine kinase (CK), creatine kinase isoenzyme (CK-MB) and lactate dehydrogenase (LDH), superoxide dismutase (SOD), and malondialdehyde (MDA), hypersensitive C-reactive protein (hs-CRP) and interleukin-1β (IL-1β) were measured. Myocardial ischemia rate, myocardial infarction rate and myocardial no-reflow rate were determined by staining with Evans blue and 2,3,5-triphenyltetrazolium chloride (TTC). Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine (BATMAN) databases were used to screen for possible active compounds of HXP and their potential therapeutic targets; the results of anti-inflammatory genes associated with MIRI were obtained from GeneCards, Drugbank, Online Mendelian Inheritance in Man (OMIM), and Therapeutic Target Datebase (TTD) databases was performed; Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were used to analyze the intersected targets; molecular docking was performed using AutoDock Tools. Western blot was used to detect the protein expression of Toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NFκB)/NOD-like receptor protein 3 (NLRP3).@*RESULTS@#Compared with the model group, all doses of HXP significantly reduced the levels of LDH, CK and CK-MB (P<0.05, P<0.01); HXP significantly increased serum activity of SOD (P<0.05, P<0.01); all doses of HXP significantly reduced the levels of hs-CRP and IL-1β (P<0.05, P<0.01) and the myocardial infarction rate and myocardial no-reflow rate (P<0.01). GO enrichment analysis mainly involved positive regulation of gene expression, extracellular space and identical protein binding, KEGG pathway enrichment mainly involved PI3K-Akt signaling pathway and lipid and atherosclerosis. Molecular docking results showed that kaempferol and luteolin had a better affinity with TLR4, NFκB and NLRP3 molecules. The protein expressions of TLR4, NFκB and NLRP3 were reduced in the HXP group (P<0.01).@*CONCLUSIONS@#HXP has a significant protective effect on myocardial ischemia-reperfusion injury in rats, and its effect may be related to the inhibition of redox response and reduction of the inflammatory response by inhibiting the TLR4NFκB/NLRP3 signaling pathway.

Mechanism of Buyang Huanwu Decoction in protecting ischemic myocardium by regulating platelet autophagy in rats with acute myocardial infarction / 中国中药杂志

This study explored the effects of Buyang Huanwu Decoction(BYHWD) on platelet activation and differential gene expression after acute myocardial infarction(AMI). SD rats were randomly divided into a sham-operated group, a model group, a positive drug(aspirin) group, and a BYHWD group. Pre-treatment was conducted for 14 days with a daily oral dose of 1.6 g·kg~(-1) BYHWD and 0.1 g·kg~(-1) aspirin. The AMI model was established using the high ligation of the left anterior descending coronary artery method. The detection indicators included myocardial infarct size, heart function, myocardial tissue pathology, peripheral blood flow perfusion, platelet aggregation rate, platelet membrane glycoprotein CD62p expression, platelet transcriptomics, and differential gene expression. The results showed that compared with the sham-operated group, the model group showed reduced ejection fraction and cardiac output, decreased peripheral blood flow, and increased platelet aggregation rate and CD62p expression, and activated platelets. At the same time, TXB_2 content increased and 6-keto-PGF1α content decreased in serum. Compared with the model group, BYHWD increased ejection fraction and cardiac output, improved blood circulation in the foot and tail regions and cardiomyocytes arrangement, reduced myocardial infarct size and inflammatory infiltration, down-regulated platelet aggregation rate and CD62p expression, reduced serum TXB_2 content, and increased 6-keto-PGF1α content. Platelet transcriptome sequencing results revealed that BYHWD regulated mTOR-autophagy pathway-related genes in platelets. The differential gene expression levels were detected using real-time quantitative PCR. BYHWD up-regulated mTOR, down-regulated autophagy-related FUNDC1 and PINK genes, and up-regulated p62 gene expression. The results demonstrated that BYHWD could regulate platelet activation, improve blood circulation, and protect ischemic myocardium in AMI rats, and its mechanism is related to the regulation of the mTOR-autophagy pathway in platelets.

Realgar (α-As4S4) Treats Myelodysplastic Syndromes through Reducing DNA Hypermethylation / 中国结合医学杂志

DNA hypermethylation is an epigenetic modification that plays a critical role in the oncogenesis of myelodysplastic syndromes (MDS). Aberrant DNA methylation represses the transcription of promotors of tumor suppressor genes, inducing gene silencing. Realgar (α-As4S4) is a traditional medicine used for the treatment of various diseases in the ancient time. Realgar was reported to have efficacy for acute promyelocytic leukemia (APL). It has been demonstrated that realgar could efficiently reduce DNA hypermethylation of MDS. This review discusses the mechanisms of realgar on inhibiting DNA hypermethylation of MDS, as well as the species and metabolisms of arsenic in vivo.

Application and Prospect of Platelet Multi-Omics Technology in Study of Blood Stasis Syndrome / 中国结合医学杂志

The abnormality of platelet function plays an important role in the pathogenesis and evolution of blood stasis syndrome (BSS). The explanation of its mechanism is a key scientific issue in the study of cardiovascular and cerebrovascular diseases and treatment. System biology technology provides a good technical platform for further development of platelet multi-omics, which is conducive to the scientific interpretation of the biological mechanism of BSS. The article summarized the pathogenesis of platelets in BSS, the mechanism of action of blood activating and stasis resolving drugs, and the application of genomics, proteomics, and metabonomics in platelet research, and put forward the concept of "plateletomics in BSS". Through the combination and cross-validation of multi-omics technology, it mainly focuses on the clinical and basic research of cardiovascular and cerebrovascular diseases; through the interactive verification of multi-omics technology and system biology, it mainly focuses on the platelet function and secretion system. The article systematically explains the molecular biological mechanism of platelet activation, aggregation, release, and other stages in the formation and development of BSS, and provides a new research idea and method for clarifying the pathogenesis of BSS and the mechanism of action of blood activating and stasis resolving drugs.

Baicalin treats cerebral ischemia reperfusion-induced brain edema in rats by inhibiting TRPV4 and AQP4 of astrocytes / 中国中药杂志

This study aims to explore the pharmacodynamic effect of baicalin on rat brain edema induced by cerebral ischemia reperfusion injury and discuss the mechanism from the perspective of inhibiting astrocyte swelling, which is expected to serve as a refe-rence for the treatment of cerebral ischemia with Chinese medicine. To be specific, middle cerebral artery occlusion(suture method) was used to induce cerebral ischemia in rats. Rats were randomized into normal group, model group, high-dose baicalin(20 mg·kg~(-1)) group, and low-dose baicalin(10 mg·kg~(-1)) group. The neurobehavior, brain index, brain water content, and cerebral infarction area of rats were measured 6 h and 24 h after cerebral ischemia. Brain slices were stained with hematoxylin and eosin(HE) for the observation of pathological morphology of cerebral cortex after baicalin treatment. Enzyme-linked immunosorbent assay(ELISA) was employed to determine the content of total L-glutathione(GSH) and glutamic acid(Glu) in brain tissue, Western blot to measure the content of glial fibrillary acidic protein(GFAP), aquaporin-4(AQP4), and transient receptor potential vanilloid type 4(TRPV4), and immunohistochemical staining to observe the expression of GFAP. The low-dose baicalin was used for exploring the mechanism. The experimental results showed that the neurobehavioral scores(6 h and 24 h of cerebral ischemia), brain water content, and cerebral infarction area of the model group were increased, and both high-dose and low-dose baicalin can lower the above three indexes. The content of GSH dropped but the content of Glu raised in brain tissue of rats in the model group. Low-dose baicalin can elevate the content of GSH and lower the content of Glu. According to the immunohistochemical staining result, the model group demonstrated the increase in GFAP expression, and swelling and proliferation of astrocytes, and the low-dose baicalin can significantly improve this situation. The results of Western blot showed that the expression of GFAP, TRPV4, and AQP4 in the cerebral cortex of the model group increased, and the low-dose baicalin reduce their expression. The cerebral cortex of rats in the model group was severely damaged, and the low-dose baicalin can significantly alleviate the damage. The above results indicate that baicalin can effectively relieve the brain edema caused by cerebral ischemia reperfusion injury in rats, possibly by suppressing astrocyte swelling and TRPV4 and AQP4.

Regulatory Effect of Quyu Huatan Tongmai Prescription on Intestinal Microflora in Golden Hamster with Hyperlipidemia / 中国实验方剂学杂志

ObjectiveTo explore the regulatory effect of Quyu Huatan Tongmai prescription on intestinal mircoflora of hyperlipidemia golden hamster and scientific evidence for the compatibility. MethodSyrian golden hamsters were randomized into normal， model， prescription， stasis-dispelling （Quyu）， phlegm-dissolving （Huatan）， and detoxification （Jiedu） groups， with 8 in each group. Hyperlipidemia in golden hamsters was induced by high-fat diet （4 weeks）. Then hamsters in the Quyu group （1.11 g·kg-1）， Huatan group （0.39 g·kg-1）， Jiedu group （0.07 g·kg-1）， and prescription group （1.42 g·kg-1） were given （ig） corresponding drugs and those in the normal group and the model group received （ig） distilled water of equivalent volume， once a day for 6 weeks. Serum lipids were determined， and hematoxylin-eosin （HE） staining was used to observe the pathological morphology of the liver. Feces were collected for 16S rRNA gene high-throughput sequencing of intestinal flora. ResultCompared with normal group， the model group demonstrated increase in body weight （P<0.05， P<0.01） and blood lipids （P<0.01）， decrease in intestinal flora diversity （P<0.05， P<0.01）， and variation of the relative abundance of intestinal flora at phylum， family， and genus levels （P<0.05， P<0.01）. Compared with the model group， Quyu Huatan Tongmai prescription controlled the body weight change， reduced the serum triglyceride （TG）， total cholesterol （TC）， and low density lipoprotein cholesterol/high density lipoprotein cholesterol ratio （LDL-C/HDL-C） （P<0.05， P<0.01）， improved the structure of intestinal flora， decreased the ratio of Firmicutes to Bacteroides （P<0.01）， raised the abundance of Bacteroidaceae， Porphyromonadaceae， Rikenellaceae， and Pasteurella （P<0.05， P<0.01）， and lowered the relative abundance of Coriobacterium （P<0.05） in hyperlipidemia golden hamsters. All the split prescriptions improved blood lipids and intestinal flora of the hamsters and particularly， the lipids-lowering effect of the Jiedu group and the regulation of flora in the Huatan group were closer to those of the prescription group. ConclusionQuyu Huatan Tongmai prescription and the split prescriptions all alleviated the hyperlipidemia of golden hamsters to different degrees possibly by regulating intestinal flora structure and improving intestinal microecology. The effect of the prescription group was most significant， and coming in second was the Huatan group. This study also provides scientific evidence for the effect of Quyu Huatan Tongmai prescription.

Effects of Qilong Capsules on myocardial fibrosis and insufficient blood circulation in ischemic cardiomyopathy with Qi deficiency and blood stasis / 中国中药杂志

Protective effect of Qilong Capsules(QL) on the myocardial fibrosis and blood circulation of rats with coronary heart disease of Qi deficiency and blood stasis type was investigated. Sleep deprivation and coronary artery ligation were used to construct a disease-symptom combination model, and 60 SD rats were divided into sham operation(sham) group, syndrome(S) group, disease and syndrome(M) group and QL group randomly. The treatment group received administration of QL 0.4 g·kg~(-1)·d~(-1). Other groups were given the same amount of normal saline. The disease indexes of each group [left ventricular end diastolic diameter(LVESD), left ventricular end systolic diameter(LVEDD), left ventricular ejection fraction(LVEF), left ventricular axis shortening rate(LVFS), myocardial histopathology, platelet morphology, peripheral blood flow] and syndrome indexes(tongue color, pulse, grip power) were detected. In sham group, cardiomyocytes and myocardial fibers were arranged neatly and densely with clear structures. The tongues' color in sham were light red, and the pulse shape were regular. RGB is a parameter reflected the brightness of the image of the tongue. In the S group, the amplitude and frequency of the animal's pulse increased accompanied by decreasing R,G,B, however, the decreased R,G,B was accompanied by reduced pulse amplitude in M group. And in M group, we observed fuzzy cell morphology, hypertrophied myocytes, disordered arrangement of cardiomyocytes and myocardial fibers, reduced peripheral blood flow and increased collagen volume fraction(CVF). Increased LVESD and LVEDD, and decreased LVEF and LVFS represented cardiac function in S group was significantly lower than that in sham. In QL group, the tongue's color was red and the pulse was smooth. The myocardial fibers of the QL group were arranged neatly and secreted less collagen. It improved the blood circulation in the sole and tail, and reversed the increasing of LVEDD, LVESD and the decreasing of LVEF and LVFS of M group. Platelets in M and S group showed high reactivity, and QL could decrease aggregation risk. In conclusion, Qilong Capsules has an obvious myocardial protective effect on ischemic cardiomyopathy, which may inhibit the degree of myocardial fibrosis and reduce platelet reactivity.

Pharmacology of combination of disease and syndrome:strategies and methods of pharmacology of Chinese medicine / 中国中药杂志

The pharmacology of Chinese medicine is an academic discipline that studies the interaction between Chinese medicine and organism(including pathogens) by modern science and technology under the guidance of traditional Chinese medicine(TCM) theories. However, the pharmacology of Chinese medicine is mainly guided by the theories, techniques, and methods of modern medicine in the development, and TCM theories have been ignored to a certain extent, which does not conform to the action characteristics of Chinese medicine in essence. Since systematic research ideas, strategies, methods, and technologies that conform to the characteristics of TCM have not been established, it is unable to reveal the scientific connotation of TCM in the prevention and treatment of diseases. Therefore, according to the trend of the modern development of TCM and the research status of pharmacology of Chinese medicine, this study put forward the concept of pharmacology of combination of disease and syndrome and expounded the relevant background, content, methods, and significance of this concept. It is expected to improve the standardization of pharmacology of combination of disease and syndrome, guide the safe medication, provide new references for the scientific development of pharmacology of Chinese medicine, and promote the development of the modernization of Chinese medicine.

Application prospects of single-cell transcriptome sequencing in traditional Chinese medicine research / 中国中药杂志

Single-cell transcriptome sequencing(scRNA-seq) can be used to analyze the expression characteristics of the transcriptome at the level of individual cell, and discover the heterogeneity of gene expression in individual cell that is "diluted" or averaged in study of group organization. The scRNA-seq, with the characteristics of standardization, high-throughput, and high integration, can greatly simplify the experimental operation and significantly reduce the consumption of reagents. At the same time, a variety of cells are screened and the gene expression patterns are analyzed at the single-cell level to provide a more efficient detection technique and more rich and accurate information for drug research. In the field of traditional Chinese medicine(TCM), the scRNA-seq is still a new technology, but the individual and precision concepts embodied by scRNA-seq and the theory of TCM syndrome differentiation and treatment have reached the same effect between the micro and macro aspects. This study tried to broaden the thinking for the modernization of TCM by introducing the development of scRNA-seq technology and its application in modern drug research and discussing the application prospects of scRNA-seq in TCM research.

Effect of Shuangshen Xionglian Granule on Vasodilation and PI3K/Akt/eNOS Pathway in Hyperhomocysteinemia Chronic Kidney Disease Rats / 中国实验方剂学杂志

Objective:To study the effect of Shuangshen Xionglian （SSXL） granules on vasculopathy and phosphatidylinositol 3 kinase （PI3K）/serine threonine kinase （Akt）/nitrogen oxide synthase （eNOS） signal in hyperhomocysteinemia chronic kidney disease rats. Method:Rats were randomly divided into 5 groups： sham operation group， model group， and high， medium and low-dose （8， 4， 2 g·kg-1） SSXL groups. The model of hyperhomocysteinemia chronic kidney disease in rats was established with high methionine feed combined with 5/6 nephrectomy. After 5/6 nephrectomy， continuous intragastric administration lasted for four weeks. Arterial blood pressure was measured at the 4th and 8th weeks after operation. At the end of the 8th week after the operation， blood was collected to determine serum creatinine， urea nitrogen， homocysteine （Hcy）， methionine and blood lipid. Western blot was used to detect the expressions of PI3K/Akt/eNOS pathway-related proteins， such as p-p85， p-Akt and p-Ser177 in thoracic aorta， and serum NO and eNOS were measured. The changes of endothelium-dependent relaxation and non-endothelium-dependent relaxation were measured by the method of isolated thoracic aorta ring. Pathological htoxylin eosin （HE） staining was used to observe the changes of renal tissue and thoracic aorta. Result:At the 8th week of the experiment， compared with the sham operation group， arterial systolic blood pressure， serum urea nitrogen， creatinine， Hcy， methionine， total cholesterol and low-density lipoprotein of the model group were significantly increased. Four weeks later after administration， arterial systolic blood pressure， serum urea nitrogen， Hcy， methionine， serum total cholesterol and serum low-density lipoprotein were significantly reduced in each dose group （P<0.05， P<0.01）. The creatinine in the SSXL 8， 4 g·kg-1 group was significantly reduced （P<0.05）. The nitric oxide content of SSXL in each dose groups were increased compared with that in the model group （P<0.05， P<0.01）， and the serum eNOS activity of the SSXL in the SSXL 8 g·kg-1 group was significantly increased compared with that in the model group （P<0.05）. The endothelium dependent and non-endothelium dependent vasodilation of thoracic aortic rings in the model group were significantly damaged. The cumulative concentration of acetylcholine （1×10-5.5~1×10-4 mmo1·L-1） in the SSXL 8 g·kg-1 group was significantly improved （P<0.05， P<0.01）. The diastolic degree of the vascular ring in the SSXL 8 g·kg-1 group was significantly higher than that in the model group （P<0.05）. Western blot results showed that the expressions of p-85， p-Akt and p-Ser177 in blood vessels increased in the sham group compared with those in the model group （P<0.01）. Compared with the model group， the phosphorylation level of this pathway was increased in the SSXL groups， and the expressions of p-Akt and p-Ser177 in the SSXL 8 g·kg-1 group were significantly increased （P<0.05）. The pathological results showed that the pathological changes of thoracic aorta and renal tissue in the dosages of SSXL were significantly reduced compared with those in the model group. Conclusion:SSXL granules can improve hyperhomocysteine and dyslipidemia in rats of chronic kidney disease with hyperhomocysteine， reduce serum creatinine， urea nitrogen levels and arterial systolic blood pressure， and improve vascular morphology and diastolic function， which may be related to the regulation of the PI3K/Akt/eNOS signaling pathway.