Lutein suppresses ferroptosis of cardiac microvascular endothelial cells via positive regulation of IRF in cardiac hypertrophy.

Cardiac microvascular dysfunction contributes to cardiac hypertrophy (CH) and can progress to heart failure. Lutein is a carotenoid with various pharmacological properties, such as anti-apoptotic, anti-inflammatory, and antioxidant effects. Limited research has been conducted on the effects of lutein on pressure overload-induced CH. Studies have shown that CH is accompanied by ferroptosis in the cardiac microvascular endothelial cells (CMECs). This study aimed to investigate the effect of lutein on ferroptosis of CMECs in CH. The transcription factor interferon regulatory factor (IRF) is associated with immune system function, tumor suppression, and apoptosis. The results of this study suggested that pressure overload primarily inhibits IRF expression, resulting in endothelial ferroptosis. Administration of lutein increased the expression of IRF, providing protection to endothelial cells during pressure overload. IRF silencing downregulated solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) expression, leading to the induction of ferroptosis in CMECs. Lutein supplementation suppressed endothelial ferroptosis by upregulating IRF. These data suggest that IRF may function as a transcription factor for SLC7A11 and that lutein represses ferroptosis in CMECs by upregulating IRF expression. Therefore, targeting IRF may be a promising therapeutic strategy for effective cardioprotection in patients with CH and heart failure.

Identification of non-coding RNA related prognosis biomarkers based on ceRNA network in thyroid cancer.

Introduction: Thyroid cancer (THCA) has become a serious malignant tumor worldwide. Identification of non-coding RNA related regulators is very necessary to improve the knowledge of THCA treatment. The aim of this study was to identify novel therapeutic targets and prognosis biomarkers for predicting pathological characteristics and subsequently treating THCA. Methods: We investigated the alterations of miRNAs, mRNAs and lncRNAs in THCA. Functional enrichment and clustering analysis were conducted for these aberrantly expressed RNAs. Multiple interaction networks among miRNAs, mRNAs and lncRNAs were constructed and the functional modules associated with THCA patients' prognosis were identified. Furthermore, we evaluated the prognostic roles of the important miRNAs, mRNAs and lncRNAs in THCA and investigated the regulatory potential of non-coding RNAs on immune cell infiltration. Results: We firstly identified that miR-4709-3p and miR-146b-3p could significantly classify patients into high/low risk groups, which may be potential prognosis biomarkers of THCA. Secondly, we constructed a THCA-related miRNA-mRNA network, which displayed small world network topological characters. Two THCA-related functional modules were identified from the miRNA-mRNA network by MCODE. Results showed that two modules could implicate in known cancer pathways, such as apoptosis and focal adhesion. Thirdly, a THCA-related miRNA-lncRNA network was constructed. A subnetwork of miRNA-lncRNA network showed strong prognosis effect in THCA. Fourthly, we constructed a THCA-related mRNA-lncRNA network and detected several typical lncRNA-miRNA-mRNA crosstalk, such as AC068138, BCL2, miR-21 and miR-146b, which had good prognosis effect in THCA. Immune infiltration results showed that lncRNAs LA16c-329F2, RP11-395N3, RP11-423H2, RP11-399B17 and RP11-1036E20 were high related to neutrophil and dendritic cell infiltration. Discussion: Non-coding RNA-mediated gene regulatory network has the strong regulatory potential in pathological processes of THCA. All these results could help us uncover the non-coding RNA-mediated regulatory mechanism in THCA.

Shear Stress Rescued the Neuronal Impairment Induced by Global Cerebral Ischemia Reperfusion via Activating PECAM-1-eNOS-NO Pathway.

Microvessel hypoperfusion following ischemic stress resulted in a decreased shear stress of brain microvascular endothelial cells (BMECs) and contributed to abnormal expression of PECAM-1 after global cerebral ischemia/reperfusion (I/R) injury. Here, we identified novel pathophysiologic and rehabilitative procedures specific to shear stress in microvascular endothelial cells in response to global cerebral I/R injury. We found that the decrease in cerebral blood flow of gerbils after global cerebral I/R injury reduces shear stress, and the abnormal change in shear stress leads to microvascular endothelial cell and neuron damage. Nevertheless, suitable high levels of shear stress contribute to rescuing the dysfunction and malformation of BMECs via regulating the PECAM-1-eNOS-NO pathway to enhance nitric oxide release, decrease the expression of caspase-3 to reduce apoptosis, and improve the shear-adaptability of endothelial cells, thereby playing a protective role in the gerbil brain.

Allicin attenuates pathological cardiac hypertrophy by inhibiting autophagy via activation of PI3K/Akt/mTOR and MAPK/ERK/mTOR signaling pathways.

BACKGROUND: Cardiac hypertrophy is an adaptive response of the myocardium to pressure or volume overload. Recent evidences indicate that allicin can prevent cardiac hypertrophy. However, it is not clear whether allicin alleviates cardiac hypertrophy by inhibiting autophagy. PURPOSE: We aimed to investigate the effects of allicin on pressure overload-induced cardiac hypertrophy, and further to clarify the related mechanism. STUDY DESIGN/METHODS: Cardiac hypertrophy was successfully established by abdominal aortic constriction (AAC) in rats, and cardiomyocytes hypertrophy was simulated by angiotensin II (Ang II) in vitro. Hemodynamic parameters were monitored by organism function experiment system in vivo. The changes of cell surface area were observed using HE and immunofluorescence staining in vivoand in vitro, respectively. The expressions of cardiac hypertrophy relative protein (BNP and ß-MHC), autophagy marker protein (LC3-II and Beclin-1), Akt, PI3K and ERK were detected by western blot. RESULTS: Allicin could improve cardiac function, and reduce cardiomyocytes size, and decrease BNP and ß-MHC protein expressions. Further results showed that allicin could lower LC3-II and Beclin-1 protein expressions both in vivo and in vitro experiments. And pharmacological inhibitor of mTOR, rapamycin could antagonize the effects of allicin on Ang II-induced cardiac hypertrophy and autophagy. Simultaneously, allicin could promote the expressions of p-Akt, p-PI3K and p-ERK protein. CONCLUSION: These findings reveal a novel mechanism of allicin attenuating cardiac hypertrophy which allicin could inhibit excessive autophagy via activating PI3K/Akt/mTOR and MAPK/ERK/mTOR signaling pathways.

Allicin improves the function of cardiac microvascular endothelial cells by increasing PECAM-1 in rats with cardiac hypertrophy.

OBJECTIVE: Cardiac microvascular damage is significantly associated with the development of cardiac hypertrophy (CH). Researchers found that allicin could inhibit CH, but the relationship between cardiac microvessel and the inhibition of allicin on CH has not been reported. We aimed to investigate the effect of allicin on the function of cardiac microvascular endothelial cells (CMECs) in CH rat. MATERIALS AND METHODS: The hemodynamic parameters were measured by BL-420F biological function experimental system and the indicators of the ventricular structure and function were measured by echocardiographic system. MTT assay was performed to assess the cell viability. Nitrite detection was performed to detect nitric oxide content. The morphology and molecular characteristics were detected by electron micrographs, immunofluorescence, quantitative real-time polymerase chain reaction (qRT-PCR), western blot. Wound healing experiment, analysis of tube formation and shear adaptation were performed to assess CMECs migration ability, angiogenesis and shear-responsiveness respectively. RESULT: Our findings have identified that microvascular density was decreased by observing the expression of platelet endothelial cell adhesion molecule-1 (PECAM-1) in CH rats. Interestingly, allicin improved the distribution and expression of PECAM-1. Meanwhile, allicin enhanced the migration and angiogenesis ability of CMECs, activated PECAM-1-PI3K-AKT-eNOS signaling pathway, however, the role of allicin was disappear after PECAM-1 was silenced. Allicin decreased the expression of caspase-3 and receptor interacting protein 3 (RIP3), inhibited necroptosis, and increased the levels of Angiopoietin-2 (Ang-2) and platelet-derived growth factor receptor-ß (PDGFR-ß). Under 10 dyn/cm2 condition, allicin advanced the modification ability of CMECs's shear-adaptation by activating PECAM-1. CONCLUSION: Allicin provided cardioprotection for CH rats by improving the function of CMECs through increasing the expression of PECAM-1.

Activation of transient receptor potential vanilloid 3 channel (TRPV3) aggravated pathological cardiac hypertrophy via calcineurin/NFATc3 pathway in rats.

Cardiac hypertrophy is a compensatory response to mechanical stimuli and neurohormonal factors, ultimately progresses to heart failure. The proteins of some transient receptor potential (TRP) channels, Ca2+ -permeable nonselective cation channel, are highly expressed in cardiomyocytes, and associated with the occurrence of cardiac hypertrophy. Transient receptor potential vanilloid 3 (TRPV3) is a member of TRP, however, the functional role of TRPV3 in cardiac hypertrophy remains unclear. TRPV3 was elevated in pathological cardiac hypertrophy, but not in swimming exercise-induced physiological cardiac hypertrophy in rats. TRPV3 expression was also increased in Ang II-induced cardiomyocyte hypertrophy in vitro, which was remarkably increased by carvacrol (a nonselective TRPV channel agonist), and reduced by ruthenium red (a nonselective TRPV channel antagonist). Interestingly, we found that activated TRPV3 in Ang II-induced cardiomyocyte hypertrophy was accompanied with increasing intracellular calcium concentration, promoting calcineurin, and phosphorylated CaMKII protein expression, and enhancing NFATc3 nuclear translocation. However, blocking or knockdown of TRPV3 could inhibit the expressions of calcineurin, phosphorylated CaMKII and NFATc3 protein by Western blot. In conclusion, the activation of TRPV3 aggravated pathological cardiac hypertrophy through calcineurin/NFATc3 signalling pathway and correlated with the protein expression levels of calcineurin, phosphorylated CaMKII and NFATc3, revealing that TRPV3 might be a potential therapeutic target for cardiac hypertrophy.

Modulation of sphingosine 1-phosphate (S1P) attenuates spatial learning and memory impairments in the valproic acid rat model of autism.

RATIONALE: Autism spectrum disorders (ASD) are a set of pervasive neurodevelopmental disorders that manifest in early childhood, and it is growing up to be a major cause of disability in children. However, the etiology and treatment of ASD are not well understood. In our previous study, we found that serum levels of sphingosine 1-phosphate (S1P) were increased significantly in children with autism, indicating that S1P levels may be involved in ASD. OBJECTIVE: The objective of this study was to identify a link between increased levels of S1P and neurobehavioral changes in autism. METHODS: We utilized a valproic acid (VPA) -induced rat model of autism to evaluate the levels of S1P and the expression of sphingosine kinase (SphK), a key enzyme for S1P production, in serum and hippocampal tissue. Furthermore, we assessed cognitive functional changes and histopathological and neurochemical alterations in VPA-exposed rats after SphK blockade to explore the possible link between increased levels of S1P and neurobehavioral changes in autism. RESULTS: We found that SphK2 and S1P are upregulated in hippocampal tissue from VPA-exposed rats, while pharmacological inhibition of SphK reduced S1P levels, attenuated spatial learning and memory impairments, increased the expression of phosphorylated CaMKII and CREB and autophagy-related proteins, inhibited cytochrome c release, decreased the expression of apoptosis related proteins, and protected against neuronal loss in the hippocampus. CONCLUSION: We have demonstrated that an increased level of SphK2/S1P is involved in the spatial learning and memory impairments of autism, and this signaling pathway represents a novel therapeutic target and direction for future studies.

Transient receptor potential vanilloid-3 (TRPV3) activation plays a central role in cardiac fibrosis induced by pressure overload in rats via TGF-ß1 pathway.

Cardiac fibrosis is a common pathologic change along with pressure overload. Recent studies indicated that transient receptor potential (TRP) channels played multiple roles in heart. However, the functional role of transient receptor potential vanilloid-3 (TRPV3) in cardiac fibrosis remained unclear. The present study was designed to investigate the relationship between TRPV3 activation and pressure overload-induced cardiac fibrosis. Pressure overload rats were successfully established by abdominal aortic constriction (AAC), and cardiac fibrosis was simulated by 100 nM angiotensin II (Ang II) in neonatal cardiac fibroblasts. Echocardiographic parameters, cardiac fibroblast proliferation, cell cycle, intracellular calcium concentration ([Ca2+] i ), and the protein expressions of collagen I, collagen III, transforming growth factor beta 1 (TGF-ß1), cyclin E, and cyclin-dependent kinase 2 (CDK2) were measured. Echocardiographic and histological measurements suggested that the activation of TRPV3 exacerbated the cardiac dysfunction and increased interstitial fibrosis in pressure overload rats. Further results showed that TRPV3 activation upregulated the expressions of collagen I, collagen III, TGF-ß1, cyclin E, and CDK2 in vivo and in vitro. At the same time, blocking TGF-ß1 pathway could partially reverse the effect of TRPV3 activation. These results suggested that TRPV3 activation exacerbated cardiac fibrosis by promoting cardiac fibroblast proliferation through TGF-ß1/CDK2/cyclin E pathway in the pressure-overloaded rat hearts.

Fingolimod (FTY720) attenuates social deficits, learning and memory impairments, neuronal loss and neuroinflammation in the rat model of autism.

AIMS: To investigate the effect of FTY720 on the valproic acid (VPA) rat model of autism. MAIN METHODS: As an animal model of autism, we used intraperitoneal injection of VPA on embryonic day 12.5 in Wistar rats. The pups were given FTY720 orally at doses of 0.25, 0.5 and 1mg/kg daily from postnatal day 15 to 35. Social behavior, spatial learning and memory were assessed at the end of FTY720 treatment. The histological change, oxidative stress, neuroinflammatory responses, and apoptosis-related proteins in the hippocampus were evaluated. KEY FINDINGS: FTY720 (1mg/kg) administration to VPA-exposed rats (1) improved social behavior, spatial learning and memory impairment; (2) resulted in a reduction in neuronal loss and apoptosis of pyramidal cells in hippocampal CA1 regions; (3) inhibited activation of microglial cells, in turn lowering the level of pro-inflammatory cytokines interleukin-1ß (IL-1ß) and IL-6 in the hippocampus; (4) changed Malondialdehyde (MDA) levels, Glutathione (GSH) levels, superoxide dismutase (SOD) activity and Glutathione Peroxidase (GSH-Px) activity in the hippocampus; (6) inhibited the elevated Bax and caspase-3 protein levels and enhanced the relative expression level of Bcl-2 in the hippocampus; and (7) increased phospho-Ca2+/calmodulin-dependent protein kinase II (p-CaMKII), phospho-cAMP-response element binding protein (p-CREB) and Brain Derived Neurotrophic Factor (BDNF) protein expression in the hippocampus. SIGNIFICANCE: FTY720 rescues social deficit, spatial learning and memory impairment in VPA-exposed rats. FTY720 exerts both a direct protection for neurons and an indirect modulation of inflammation-mediated neuron loss as a possible mechanism of neuroprotection.

Maternal DHA supplementation protects rat offspring against impairment of learning and memory following prenatal exposure to valproic acid.

Docosahexaenoic acid (22:6n-3; DHA) is known to play a critical role in postnatal brain development. However, there have been no studies investigating the preventive effect of DHA on prenatal valproic acid (VPA)-induced behavioral and molecular alterations in offspring. The present study was to evaluate the neuroprotective effects in offspring using maternal feeding of DHA to rats exposed to VPA in pregnancy. In the present study, rats were exposed to VPA on day 12.5 of pregnancy; DHA was administered at the dosages of 100, 300 and 500 mg/kg/day for 3 weeks from day 1 to 21 of pregnancy. The results showed that maternal feeding of DHA to the prenatal exposed to VPA (1) prevented VPA-induced learning and memory impairment but did not change social-related behavior, (2) increased total DHA content in offspring plasma and hippocampus, (3) rescued VPA-induced neuronal loss and apoptosis of pyramidal cells in hippocampal CA1, (4) influenced the content of malondialdehyde and glutathione and the activities of superoxide dismutase and glutathione in the hippocampus, (5) altered levels of apoptosis-related proteins (Bcl-2, Bax and caspase-3) and inhibited the activity of caspase-3 in offspring hippocampus and (6) enhanced relative levels of p-CaMKII and p-CREB proteins in the hippocampus. These findings suggest that maternal feeding with DHA may prevent prenatal VPA-induced impairment of learning and memory, normalize several different molecules associated with oxidative stress and apoptosis in the hippocampus of offspring, and exert preventive effects on prenatal VPA-induced brain dysfunction.

Neuroprotective effects of docosahexaenoic acid on hippocampal cell death and learning and memory impairments in a valproic acid-induced rat autism model.

Prenatal exposure to valproic acid (VPA) in rat offspring is capable of inducing experimental autism with neurobehavioral aberrations. This study investigated the effect of docosahexaenoic acid (DHA) on hippocampal cell death, learning and memory alteration in an experimental rat autism model. We found that DHA supplementation (75, 150 or 300 mg/kg/day, 21 days) rescued the VPA (600 mg/kg) induced DHA reduction in plasma and hippocampus in a dose-dependent manner, increased the levels of hippocampal p-CaMKII and p-CREB without affecting total protein level, and altered BDNF-AKT-Bcl-2 signaling pathway, as well as inhibited the activity of caspase-3. DHA also influenced the content of malondialdehyde (MDA) and the activities of antioxidant enzymes in the VPA-treated offspring. Consistent with the previous results, we also observed that 300 mg/kg DHA supplementation markedly increased the cell survival, decreased the cell apoptosis, and increased mature neuronal cell in the hippocampus in VPA-treated offspring. Utilizing the Morris water maze test, we found that DHA prevented cognitive impairment in offspring of VPA-treated rats. The data suggested that DHA may play a neuroprotective role in hippocampal neuronal cell and ameliorates dysfunctions in learning and memory in this rat autism model. Thus, DHA could be used as treatment intervention for mitigating behavioral dysfunctions in autism spectrum disorder (ASD).

Potential serum biomarkers from a metabolomics study of autism.

BACKGROUND: Early detection and diagnosis are very important for autism. Current diagnosis of autism relies mainly on some observational questionnaires and interview tools that may involve a great variability. We performed a metabolomics analysis of serum to identify potential biomarkers for the early diagnosis and clinical evaluation of autism. METHODS: We analyzed a discovery cohort of patients with autism and participants without autism in the Chinese Han population using ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF MS/MS) to detect metabolic changes in serum associated with autism. The potential metabolite candidates for biomarkers were individually validated in an additional independent cohort of cases and controls. We built a multiple logistic regression model to evaluate the validated biomarkers. RESULTS: We included 73 patients and 63 controls in the discovery cohort and 100 cases and 100 controls in the validation cohort. Metabolomic analysis of serum in the discovery stage identified 17 metabolites, 11 of which were validated in an independent cohort. A multiple logistic regression model built on the 11 validated metabolites fit well in both cohorts. The model consistently showed that autism was associated with 2 particular metabolites: sphingosine 1-phosphate and docosahexaenoic acid. LIMITATIONS: While autism is diagnosed predominantly in boys, we were unable to perform the analysis by sex owing to difficulty recruiting enough female patients. Other limitations include the need to perform test-retest assessment within the same individual and the relatively small sample size. CONCLUSION: Two metabolites have potential as biomarkers for the clinical diagnosis and evaluation of autism.

[The risk factors of chronic obstructive pulmonary disease in Heilongjiang province].

OBJECTIVE: To study the prevalence and risk factors of chronic obstructive pulmonary disease (COPD) in Heilongjiang province. METHODS: This was a population-based and cross-sectional survey on prevalence of COPD in Heilongjiang province from September 2013 to March 2014. The stratified-cluster-random sampling method was performed to collect the data from 4 478 people in 5 cities (Jixi, Daqing, Suihua, Yichun and Jiagedaqi). The subjects were interviewed with questionnaires and tested with spirometry. A post-bronchodilator FEV1/FVC<70% was defined as diagnostic of COPD. RESULTS: Completed and qualified data were obtained from 4 059 participants. The average prevalence of COPD was 7.3% (urban 6.0%; rural 8.8%; men 8.6%; women 6.5%). When using SPSS18.0 for the single factors logistic regression analysis, results indicated that sex (OR = 0.700, 95%CI:0.540-0.907), age ≥ 50 (OR = 1.236, 95%CI:0.758-2.017), lower education level (OR = 1.551, 95%CI:0.929-2.590), biomass for cooking (compared with electricity, OR = 2.744, 95%CI:1.429-5.271), biomass (compared with centralized heat supply, OR = 1.229, 95%CI:0.120-12.546)and coal (compared with centralized heat supply, OR = 4.661, 95%CI:0.474-45.840) for heating, respiratory diseases (OR = 3.594, 95%CI:2.738-4.716), combined with cardiovascular disease (OR = 1.370, 95%CI:1.058-1.776) were the risk factors of COPD in Heilongjiang province. CONCLUSION: Higher risk for COPD was related with sex, age, education level, cooking fuel, heating methods, respiratory diseases and combined with cardiovascular disease.

Study of the serum levels of polyunsaturated fatty acids and the expression of related liver metabolic enzymes in a rat valproate-induced autism model.

To investigate whether the decreased level of serum polyunsaturated fatty acids (PUFAs) in patients with autism is associated with the expression of related liver metabolic enzymes, we selected rats that were exposed to valproic acid (VPA) on embryonic day 12.5 (E12.5) as a model of autism. We observed the serum levels of PUFAs and the expression of related liver metabolic enzymes, including Δ5-desaturase, Δ6-desaturase and elongase (Elovl2), in VPA-exposed and control rats on postnatal day 35 (PND35) and conducted sex dimorphic analysis. We found that the levels of serum PUFAs and related liver metabolic enzymes in the VPA rats were significantly reduced, in association with autism-like behavioral changes, the abnormal expression of apoptosis-related proteins and hippocampal neuronal injury, compared to the control rats and showed sex difference in VPA group. This finding indicated that rats exposed to VPA at the embryonic stage may exhibit reduced synthesis of serum PUFAs due to the down-regulation of liver metabolic enzymes, thereby inducing nervous system injury and behavioral changes, which is affected by sex in the meantime.

The mechanism of neurogenic pulmonary edema in epilepsy.

Neurogenic pulmonary edema (NPE) is found in many epilepsy patients at autopsy. It is a life-threatening complication, known for almost 100 years, but its etiopathogenesis is still not completely understood. In this study, we used the tremor rat (TRM: tm/tm) as an animal model of epilepsy to investigate the potential mechanisms of NPE under epileptic conditions. We performed reverse-phase high-pressure liquid chromatography assay, H&E and Masson staining, TUNEL assay, and Western blot experiments to determine the role of seizures in NPE. We found the level of catecholamine was higher in TRM rats. Also the occurrence of alveolar cell apoptosis was increased. Moreover, pulmonary vascular remodeling including the deposition of collagen and medial thickening was also found in TRM rats. Further study showed that cell apoptosis was mediated by increasing Bax, decreasing Bcl-2, and activating caspase-3. In addition, the protein level of phosphorylated ERK (p-ERK) was found to be decreased while phosphorylated JNK and phosphorylated p38 were upregulated in TRM rats. Thus, these findings suggest that pulmonary vascular remodeling and alveolar cell apoptosis might be involved in epilepsy-induced NPE and that the mitogen-activated protein kinase signal pathway was involved.

Baicalin attenuates global cerebral ischemia/reperfusion injury in gerbils via anti-oxidative and anti-apoptotic pathways.

Baicalin is an important medicinal herb purified from the dry roots of Scutellaria baicalensis Georgi. The present study was undertaken to evaluate the neuroprotective effects of baicalin in gerbils subjected to transient global cerebral ischemic-reperfusion injury. Baicalin at doses of 50, 100 and 200mg/kg was intraperitoneally injected into the gerbils immediately after cerebral ischemia. Seven days after reperfusion, hematoxylin and eosin (HE) staining was performed to analyze hippocampal CA1 pyramidal damage histopathologically. In addition, in order to understand the potential protective mechanism of baicalin, we examined anti-oxidative enzymes, such superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), non-enzymatic scavenger glutathione (GSH) and measured the content of malondialdehyde (MDA) in hippocampus. The mRNA and protein expressions of BDNF were determined in ischemic hippocampus by real-time RT-PCR and Western blot, respectively. Evidence for neuronal apoptosis was detected by real-time RT-PCR, Western blot and caspase-3 activity measurement. Histopathological examination showed that the administration of baicalin by the dose of 100 and 200mg/kg significantly attenuated ischemia-induced neuronal cell damage. Reduced level of MDA, obviously elevated activities of SOD and GSH as well as GSH-PX were also found in baicalin-treated groups. Further investigation demonstrated that treatment with baicalin remarkably promoted the expression of BDNF and inhibited the expression of caspase-3 at mRNA and protein levels by real-time RT-PCR and Western blot, respectively. Besides, caspase-3 activity assay also elucidated that the administration of baicalin could significantly suppress caspase-3 in ischemic gerbils hippocampus. Theses findings suggest that baicalin's neuroprotection appears to be associated with its anti-oxidative and anti-apoptotic properties in global cerebral ischemia in the gerbils.

Antiarrhythmic effects and ionic mechanisms of oxymatrine from Sophora flavescens.

Accumulating evidence indicates that oxymatrine may exert protective effects on the cardiovascular system. This study was designed to evaluate the antiarrhythmic effects as well as the electrophysiological properties of oxymatrine. The antiarrhythmic activity of oxymatrine was observed in a rat model of arrhythmia induced by coronary ligation. Action potential duration (APD), L-type calcium current (I(Ca-L) ), transient outward potassium current (I(to) ) and inward rectifier potassium current (I(K1)) in rat ventricular myocytes were recorded by utilizing the whole cell patch-clamp technique. The results showed that administration of oxymatrine significantly delayed the onset of ventricular arrhythmia, decreased the duration of ventricular arrhythmia and reduced the arrhythmia score of arrhythmic rats. The beneficial effects of oxymatrine may be related to the shortening of APD through reduction of I(Ca-L) , enhancement of I(to) and inhibition of I(K1).