Down-regulation of SIK2 expression alleviates myocardial ischemia-reperfusion injury in rats by inhibiting autophagy through the mTOR-ULK1 signaling pathway / 南方医科大学学报

OBJECTIVE@#To explore the role of salt-inducible kinase 2 (SIK2) in myocardial ischemia-reperfusion (IR) injury in rats.@*METHODS@#Fifteen male SD rats were randomized equally into sham operation group, myocardial IR model group, and SIK2 inhibitor group (in which the rats were treated with intravenous injection of 10 mg/kg bosutinib via the left femoral vein 24 h before modeling). Ultrasound was used to detect the cardiac function of the rats, and myocardial pathologies were observed with HE staining. Transmission electron microscopy was used to observe autophagy of myocardial cells, and Western blotting was performed to detect the contents of the autophagy-related proteins SIK2, LC3B, Beclin-1, p62 and the expressions of p-mTOR, mTOR, p-ULK1, and ULK1 in myocardial tissue.@*RESULTS@#Myocardial IR injury significantly increased the number of autophagosomes (P < 0.05) and the expression of SIK2 protein (P < 0.01) in the myocardial tissues. Treatment with bosutinib before modeling obviously lowered the expression of SIK2 protein (P < 0.01), alleviated myocardial pathologies, and reduced the number of autophagosomes (P < 0.05) in the myocardial tissue. The rats with myocardial IR injury showed obviously lowered LVEF and FS values (P < 0.001), which were significantly improved by bosutinib treatment (P < 0.05); no significant difference was detected in IVSDd or LVPWDd among the 3 groups (P > 0.05). Myocardial IR injury obviously increased the expressions of LC3-II/LC3-I and Beclin-1 proteins and lowered the expression of p62 protein (P < 0.01), and these changes were significantly rescued by bosutinib treatment (P < 0.05). The rat models of myocardial IR injury showed significantly increased expression of p-ULK1 (Ser757) (P < 0.01) and lowered expression of p-mTOR protein (P < 0.0001) in the myocardium, and these changes were obviously reversed by bosutinib (P < 0.01 or 0.05); there was no significant difference in mTOR and ULK1 expressions among the 3 groups (P > 0.05).@*CONCLUSION@#SIK2 may promote autophagy through the mTOR/ULK1 signaling pathway, and inhibiting SIK2 can reduce abnormal autophagy and alleviate myocardial IR injury in rats.

Research on mechanism of abnormal cerebrovascular cell communication and brain diseases / 中国药理学通报

Brain diseases such as stroke, Alzheimer s disease, epilepsy, have always been worldwide problems that endanger human health and are costly disease from societal perspectives. In recent years, more and more attention has been paid to the relationship between components of neurovascular unit (cerebrovascular endothelial cell, microglia, astrocyte and neuron) and brain diseases. Not only have their structures changed during the pathological process, but also coupling communication and functions have changed accordingly. On the basis of summarizing previous studies on the abnormalities in intercellular communication and its mechanism with brain disorders, this review is expected to find novel targets or therapeutic treatment for neuropsychiatric diseases.

Study on active components and targets of Ginseng in Prevention and treatment of PTSD based on Network Pharmacology / 中国药理学通报

Aim To obtain the active components and targets of ginseng in the prevention and treatment of traumatic stress disorder(PTSD) through the method of network pharmacology. Methods The active components and target information of ginseng with medicinal value were obtained by TCMSP research platform, and the gene information closely related to the pathogenesis of PTSD was obtained by searching GeneCard and OMIM database. The two were matched to obtain the medicinal components and target genes of ginseng in the prevention and treatment of PTSD. The drug-dis- ease-target network diagram was drawn by R and Perl computer languages, and the target genes were analyzed by PPI network analysis, gene ontology ( GO ) and signal transduction pathway ( KEGG) enrichment analysis. Results According to the general pharmacological research methods of traditional Chinese medi cine, the screening parameters of active components were set, and nine kinds of high value medicinal ingredients of Panax ginseng were obtained. There was a drug-target relationship between the nine medicinal components and sixteen target genes related to PTSD disease. Through PPI, GO and KEGG analysis, it was found that the target genes were mainly enriched in physiological functions such as neurotransmitters, syn-aptic plasticity, ion channels and so on. Conclusions Ginseng has the pharmacological effect of preventing and treating PTSD, which may play a role in regulating the metabolism and receptor activity of monoamine neurotransmitters.

Identification of aminoalcohol-diterpenoid alkaloids in Aconiti Lateralis Radix Praeparata and study of their cardiac effects / 药学学报

In order to affirm the cardioactive components in Fuzi, we identified a group of aminoalcohol- diterpenoid alkaloids in Fuzi using ultra high-performance liquid chromatography coupled with electrospray ionization mass spectrometer (UPLC-ESI-MS) method. Among a total of forty-one isolated ingredients, thirteen major aminoalcohol-diterpenoid alkaloids were identified by comparing their retention times and MS spectra with those of the reference substances. Moreover, Fuzi samples from different places of origin and with different processing methods were examined and their components displayed a pattern of high similarity, though the relative abundance varies probably due to their different processing methods. Furthermore, the cardiac effect of each identified alkaloid was individually evaluated using the isolated bullfrog heart perfusion experiment. Among the thirteen aminoalcohol diterpenoid alkaloids tested, six of them significantly enhanced the amplitude rates. Taken together, we affirm that the cardioactive components in Fuzi are aminoalcohol-diterpenoid alkaloids, shedding light on future studies of the mechanisms and development of these cardioactive compounds.

Determination of alkaloids in Radix Aconiti Lateralis Preparata by RP-ion-pair HPLC / 药学学报

<p><b>AIM</b>To separate and quantitatively determine six alkaloids: aconitine, mesaconitine, hypaconitine, beiwutine, benzoylaconine and benzoylmesaconine in the Chinese traditional medicine Radix Aconiti Lateralis Preparata (Fuzi).</p><p><b>METHODS</b>A RP-ion-pair HPLC method was established. An AichromBond-1 C18 column was used at a column-temperature of 35 degrees C. The mobile phase was CH3CN5 mmol x L(-1) NaH2PO4(50:50) containing 7 mmol x L(-1) SDS at a flow-rate of 1.0 mL x min(-1). The detector was set at UV 235 nm.</p><p><b>RESULTS</b>These six alkaloids can be completely separated and determined quantitatively.</p><p><b>CONCLUSION</b>This method is accurate and suitable for the determination of six alkaloids in Fuzi.</p>