The efficacy and safety of Chinese herbal medicine for mild cognitive impairment: a systematic review and meta-analysis of randomized placebo-controlled trials.

Objective: Effective and safe treatments for mild cognitive impairment (MCI) are limited. Chinese herbal medicine (CHM) is commonly used in China to manage MCI. However, its efficacy and safety remain uncertain. This review aims to evaluate the efficacy and safety of CHM for MCI. Methods: Nine databases were searched from their inceptions to January 2023. Randomized, placebo-controlled trials of oral CHM for MCI were included. Study quality was assessed using the Cochrane risk-of-bias tool 2.0, and the certainty of evidence was evaluated via the GRADE approach. Results: Thirteen studies, involving 1,043 participants, were analyzed. Most of the studies (10 out of 13) were associated with "some concerns" regarding the overall risk of bias. Meta-analyses results indicated that CHM significantly improved cognitive function compared to placebo in terms of Mini-Mental State Examination (MMSE) (MD: 1.90 [1.22, 2.58], I2 = 87%, 11 studies, 823 participants) and Montreal Cognitive Assessment (MoCA) (MD: 2.88 [1.69, 4.06], I2 = 81%, 3 studies, 241 participants). The certainty of evidence for MMSE was assessed as "moderate", while it was "low" for MoCA. One study did not report adverse events (AEs), one study reported no statistical difference between the groups in terms of AEs, and 11 studies provided detailed numbers of AE cases where gastrointestinal symptoms were the most commonly reported AEs. Two studies reported no SAEs among participants and one study found no significant difference in SAEs proportions between groups. The meta-analysis revealed no significant difference in AEs between the two groups (RR: 1.31 [0.92, 1.87), I2 = 0%, 11 studies, 839 participants). The cognitive-enhancing function of commonly used herbs (Panax ginseng C.A.Mey., Acorus calamus var. angustatus Besser, and Polygala tenuifolia Willd.) may be attributed to mechanisms including antioxidant, anti-apoptotic, anti-neurotoxic, anti-cytotoxic, and anti-inflammatory actions. Conclusion: Chinese herbal medicine holds potential as an effective intervention to improve cognitive function in MCI patients, supported by meta-analyses evidence of low to moderate certainty. Although current data suggests CHM is generally safe, caution is advised due to the lack of AE reporting or detailed information in some instances. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=400292, identifier [CRD42023400292].

Polyvinyl alcohol films incorporated with clove essential oil emulsions stabilized by soy protein isolate-derived amyloid fibrils: Fabrication, characterization, and its application for active packaging.

This study aimed to prepare a novel emulsion film with high stability, using soy protein-derived amyloid fibrils (SAFs) as an emulsifier incorporating clove essential oil (CEO) as the active component, and the polyvinyl alcohol (PVA) matrix to stabilize the system. The results demonstrated that SAFs can successfully stabilize CEO. Emulsion prepared by SAFS and CEO (SAC) exhibited a small droplet size and better dispersibility compared with SPI and CEO (SC) emulsion. According to FT-IR results, PVA addition increased the hydrogen bond interactions among emulsion film components, thus further reinforcing the protein matrix, increasing the tensile strength (TS) (41.18 MPa) and elongation at break (E) (121.62 %) of the films. The uniform appearance of SAC-PVA (SACP) emulsion films was confirmed by SEM images. Furthermore, SACP emulsion films show distinctive barrier properties, optical properties, and outstanding antioxidant properties. Finally, emulsion films exhibited excellent preservation of strawberries, resulting in an effective decline of the decay rate.

[Rapid detection technology of chemical component content in Lycii Fructus based on hyperspectral technology].

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Partial compression increases acidity, but decreases phenolics in jujube fruit: Evidence from targeted metabolomics.

Jujube fruit (Ziziphus jujuba Mill.) is extremely susceptible to mechanical injury by extrusion and collision during storage, transportation and processing. In this study, we examined the morphology and endogenous metabolism of jujubes at three developmental stages after applying partial compression (PC) to mimic mechanical injury. Generally, PC did not affect the total soluble solids content, but increased the acidity and decreased the amount of phenolics in the jujube fruit. Targeted metabolomics analysis further confirmed that acid and phenolics content were differentially altered in response to PC. To our knowledge, this is the first study to characterize metabolic variations in ready-to-eat fruit that occur in response to physical damage. The results will provide insight into the understanding the consequences of mechanical injury on fruit nutrition and health benefits.

Glabridin, a bioactive component of licorice, ameliorates diabetic nephropathy by regulating ferroptosis and the VEGF/Akt/ERK pathways.

BACKGROUND: Glabridin (Glab) is a bioactive component of licorice that can ameliorate diabetes, but its role in diabetic nephropathy (DN) has seldom been reported. Herein, we explored the effect and underlying mechanism of Glab on DN. METHODS: The bioactive component-target network of licorice against DN was by a network pharmacology approach. The protective effect of Glab on the kidney was investigated by a high-fat diet with streptozotocin induced-diabetic rat model. High glucose-induced NRK-52E cells were used for in vitro studies. The effects of Glab on ferroptosis and VEGF/Akt/ERK pathways in DN were investigated in vivo and in vitro using qRT-PCR, WB, and IHC experiments. RESULTS: Bioinformatics analysis constructed a network comprising of 10 bioactive components of licorice and 40 targets for DN. 13 matching targets of Glab were mainly involved in the VEGF signaling pathway. Glab treatment ameliorated general states and reduced FBG, HOMA-ß, and HOMA-insulin index of diabetic rats. The renal pathological changes and the impaired renal function (the increased levels of Scr, BUN, UREA, KIM-1, NGAL, and TIMP-1) were also improved by Glab. Moreover, Glab repressed ferroptosis by increasing SOD and GSH activity, and GPX4, SLC7A11, and SLC3A2 expression, and decreasing MDA and iron concentrations, and TFR1 expression, in vivo and in vitro. Mechanically, Glab significantly suppressed VEGF, p-AKT, p-ERK1/2 expression in both diabetic rats and HG-induced NRK-52E cells. CONCLUSIONS: This study revealed protective effects of Glab on the kidney of diabetic rats, which might exert by suppressing ferroptosis and the VEGF/Akt/ERK pathway.

Succinate dehydrogenase/complex II is critical for metabolic and epigenetic regulation of T cell proliferation and inflammation.

Effective T cell-mediated immune responses require the proper allocation of metabolic resources to sustain growth, proliferation, and cytokine production. Epigenetic control of the genome also governs T cell transcriptome and T cell lineage commitment and maintenance. Cellular metabolic programs interact with epigenetic regulation by providing substrates for covalent modifications of chromatin. By using complementary genetic, epigenetic, and metabolic approaches, we revealed that tricarboxylic acid (TCA) cycle flux fueled biosynthetic processes while controlling the ratio of succinate/α-ketoglutarate (α-KG) to modulate the activities of dioxygenases that are critical for driving T cell inflammation. In contrast to cancer cells, where succinate dehydrogenase (SDH)/complex II inactivation drives cell transformation and growth, SDH/complex II deficiency in T cells caused proliferation and survival defects when the TCA cycle was truncated, blocking carbon flux to support nucleoside biosynthesis. Replenishing the intracellular nucleoside pool partially relieved the dependence of T cells on SDH/complex II for proliferation and survival. SDH deficiency induced a proinflammatory gene signature in T cells and promoted T helper 1 and T helper 17 lineage differentiation. An increasing succinate/α-KG ratio in SDH-deficient T cells promoted inflammation by changing the pattern of the transcriptional and chromatin accessibility signatures and consequentially increasing the expression of the transcription factor, PR domain zinc finger protein 1. Collectively, our studies revealed a role of SDH/complex II in allocating carbon resources for anabolic processes and epigenetic regulation in T cell proliferation and inflammation.

Determination of the Minimum Infusion Rate of Alfaxalone Combined with Electroacupuncture in Goats.

Total intravenous anesthesia (TIVA) is increasingly used in companion animals. The effect of electroacupuncture (EA) on alfaxalone-based TIVA has not been previously reported in goats. Therefore, the objective of this study was to determine the minimum infusion rate (MIR) of alfaxalone required to prevent purposeful movement of the extremities in response to standardized noxious stimulation during its combination with EA in goats. Twelve clinically healthy goats weighing 18.5 ± 2 kg were randomly assigned to two groups (six goats/group). Alfaxalone alone (ALF group) and alfaxalone combined with EA (EA-ALF group). In the EA-ALF, alfaxalone was administered 30 min after EA stimulation. For induction of anesthesia, a bolus of alfaxalone was given at 3 mg/kg IV, and an infusion dose of 9.6 mg/kg/h was initially set for maintenance. The MIR of alfaxalone in both groups was determined by testing for responses to stimulation (clamping on a digit with Vulsellum forceps) at 10-min intervals after induction of anesthesia till the entire period of the experiment. Cardiopulmonary parameters and nociceptive threshold were measured throughout anesthesia. The median alfaxalone MIR was significantly lower in the EA-ALF group than the ALF group [9 (4.8-9.6) and 12 (11.4-18)], respectively; p = 0.0035). In the ALF group, goats anesthetized with MIR showed a significant increase in heart rate and cardiac output (p < 0.0001 and 0.0312, respectively), and decrease in respiratory rate (p < 0.0001), hemoglobin oxygen saturation (p = 0.0081), and rectal temperature (p = 0.0046) compared with those in the EA-ALF. Additionally, goats in the EA-ALF showed a higher nociceptive threshold than those in the ALF group (p < 0.0001). EA provided analgesia, reduced the MIR of alfaxalone-based IV anesthesia and thereby alleviated the adverse cardiorespiratory effects associated with alfaxalone anesthesia in goats.

Simiao Qingwen Baidu decoction inhibits Epstein-Barr virus-induced B lymphoproliferative disease and lytic viral replication.

CONTEXT: Simiao Qingwen Baidu decoction (SQBD), a traditional Chinese medicine prescription, can ameliorate Epstein-Barr virus (EBV) induced disease. However, its mechanism still remains unknown. OBJECTIVE: To detect the mechanism of SQBD in EBV-induced B lymphoproliferative disease in vitro. MATERIALS AND METHODS: Sprague-Dawley (SD) rats (n = 20) were given SQBD (10 mL/kg) by gavage once a day for 7 d. SQBD-containing serum was obtained from abdominal aortic blood of rats, and diluted with medium to obtain 5%, 10% or 20%-medicated serum. SD rats (n = 10) were given normal saline, and normal serum was collected as a control. EBV-transformed B cells (CGM1) were cultured in medium containing 5%, 10% or 20%-medicated serum. CGM1 cells were treated with normal serum as a control. Cell viability and apoptosis were examined. The expression and activity of proteins were assessed. RESULTS: We found that IC50 (83 ± 26.07%, 24 h; 69.88 ± 4.69%, 48 h) of 10% medicated serum was higher than that of 5% (25.47 ± 6.98%, 24 h; 21.62 ± 7.30%, 48 h) and 20%-medicated serum (51 ± 7.25%, 24 h; 56.03 ± 2.56%, 48 h). Moreover, SQBD promoted apoptosis of CGM1 cells by regulating EBV latency proteins expression. SQBD inhibited EBV-induced lytic viral replication. CONCLUSIONS: Our data confirmed that SQBD inhibits EBV-induced B lymphoproliferative disease and lytic viral replication. This work provides a theoretical basis for the mechanism of SQBD in EBV-induced B lymphoproliferative disease, and SQBD may be an effectively therapeutic drug for EBV-induced B lymphoproliferative disease.

Survey of mineral oil hydrocarbons in Chinese commercial complementary foods for infants and young children.

Recently, mineral oil hydrocarbons (MOH) in various foods have raised significant concern, especially for infants and young children due to their potential adverse health effects. Two fractions can be distinguished by certain analytical techniques, mineral oil saturated hydrocarbons (MOSH) and mineral oil aromatic hydrocarbons (MOAH). The toxicological profile of MOSH and MOAH differs greatly. The toxicity of MOSH is linked with long-term accumulation of some hydrocarbons. MOAH with three to seven, non- or simple-alkylated, aromatic rings may be mutagenic and carcinogenic. However, data on the occurrence of mineral oils in commercial complementary foods for infants and young children are lacking in China. In the present study, 100 commercial food samples were collected, including 26 pureed or paste canned foods, 21 high-protein ground cereal foods (rice flour), 25 raw cereal foods (noodles), and 28 cereal-based molar sticks and biscuits. The content of MOSH and MOAH in those samples was determined by optimised sample preparation methods combined with on-line high-performance liquid chromatography coupled with gas chromatography and flame ionisation detector (HPLC-GC-FID), with a limit of quantification of 0.5 mg/kg. The results indicated that there were no MOAH detected in any of the foods, but MOSH and polyolefin oligomeric saturated hydrocarbons (POSH) existed in most of the food samples, at <0.5-23.68 mg/kg. Moreover, the data and chromatograms of the MOSH and POSH also indicated that these contaminants were closely correlated to their ingredients and manufacturers. The current study provides basic data to understand MOH exposure and consequent health impact.

Inhibitory effect of simiao qingwen baidu decoction on epstein-barr virus EA, VCA expression and DNA replication in vitro.

This article aims to investigate the role of Simiao Qingwen Baidu Decoction (traditional Chinese medicine) in Epstein-Barr virus (EBV)-induced infectious mononucleosis. Sprague Dawley rats were given Simiao Qingwen Baidu Decoction by gavage, and the medicated serum was collected. EBV-latent infected human Burkitt lymphomas Raji and EBV-transformed marmosets B lymphoblast cell B95-8 were treated with medicated serum. CCK8 assay and flow cytometry were performed to detect cell proliferation and apoptosis. Indirect immunofluorescence assay was performed to analyze EA or VCA positive expression. The copy-number of EBV-DNA and the gene expression were detected by quantitative PCR or quantitative real-time PCR. We found that the medicated serum inhibited proliferation of Raji and B95-8 cells, especially 10 %-medicated serum. The 10 %-medicated serum significantly suppressed EA expression in Raji cells and VCA expression in B95-8 cells. The expression of BZLF1, BRLF1, BMLF1 and EBNA-1 in Raji cells was significantly inhibited by 10 %-medicated serum. 10 %-medicated serum caused a decrease in the copy-number of EBV-DNA in Raji cells. In conclusion, our data imply that Simiao Qingwen Baidu Decoction represses the expression of EA and VCA, and EBV-DNA replication. Thus, our work suggests that Simiao Qingwen Baidu Decoction may play a vital role in anti-EBV.

A Network Pharmacology Approach to Investigate the Active Compounds and Mechanisms of Musk for Ischemic Stroke.

OBJECTIVES: This study aims to study the material basis and effective mechanism of musk for ischemic stroke (IS) based on the network pharmacology approach. METHODS: We collected the chemical components and target gene of musk from the BATMAN-TCM analytical platform and identified ischemic stroke-related targets from the following databases: DisGeNET, NCBI-Gene, HPO, OMIM, DrugBank, and TTD. The targets of musk and IS were uploaded to the String database to construct the protein-protein interaction (PPI) network, and then, the key targets were analyzed by topological methods. At last, the function biological process and signaling pathways of key targets were carried out by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and cluster analysis by using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) server and Metascape platform. RESULTS: A total of 29 active compounds involving 1081 predicted targets were identified in musk and there were 1104 IS-related targets. And 88 key targets of musk for IS were obtained including AKT1, MAPK1/3, TP53, TNF, SRC, FOS, CASP3, JUN, NOS3, and IL1B. The GO and KEGG enrichment analysis suggested that these key targets are mainly involved in multiple pathways which participated in TNF signaling pathway, estrogen signaling pathway, prolactin signaling pathway, neurotrophin signaling pathway, T-cell receptor signaling pathway, cAMP signaling pathway, FoxO signaling pathway, and HIF1 signaling pathway. CONCLUSION: This study revealed that the effective mechanisms of musk against IS would be associated with the regulation of apoptosis, inflammatory response, and gene transcription.

Soufeng Yuchuan decoction mitigates the ovalbumin-induced lung damage in a rat model of asthma.

Airway remodeling is a key feature of asthma. Extracellular matrix synthesis and vascular remodeling respectively regulated by transforming growth factor (TGF-ß1) and vascular endothelial growth factor (VEGF), are important for the airway remodeling. This study aimed to investigate the effect of Soufeng Yuchuan (SFYC) decoction, a Traditional Chinese Medicine, on airway remodeling and expression of VEGF and TGF-ß1 in asthma model rats. A rat model of asthma was induced by ovalbumin (OVA) treatment. The results showed that SFYC decoction improved general conditions and reduced the damage in lung tissues in asthma model rats. Furthermore, SFYC decoction significantly reduced the OVA-induced levels of VEGF and TGF-ß1 in sera and in bronchoalveolar lavage fluid. Moreover, SFYC decoction decreased the OVA-induced VEGF mRNA and protein levels in lung tissues in asthma model rats. Interestingly, SFYC with high dose was more potent in reducing TGF-ß1 level in rat sera and BALF than dexamethasone (positive control). In summary, SFYC decoction effectively mitigates lung damage in OVA-induced asthma model rats, which was associated with inhibition of VEGF and TGF-ß1.

In vitro investigation of the influence of nano-cellulose on starch and milk digestion and mineral adsorption.

Three types of nanocellulose, namely nano-fibrilated cellulose (NFC, also called cellulose nano-fibrils (CNF)), TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl radical) oxidized cellulose nano-fibrils (TEMPO-CNF), and nano-crystalline cellulose (NCC, also called cellulose nano-crystals (CNC)), were studied in terms of their effects on in vitro milk digestion and mineral adsorption. The effects of anionic NC (TEMPO-CNF and CNC) on in vitro starch digestion and glucose diffusion were also investigated. Results show that TEMPO-CNF and CNC at high concentrations caused significant reductions in glucose diffusion, especially at 0.36% (w/w) TEMPO-CNF and 2-4% (w/w) CNC. In addition, CNF and TEMPO-CNF at 0.30% (w/w) significantly reduced the amount of free fatty acid produced during intestinal digestion of milk fat. CNC at a concentration of 0.3% (w/w) delayed diffusion of free amino nitrogen during intestinal digestion of milk protein. All three types of NC adsorbed significant amount of Fe, and CNC adsorbed significant amount of Zn, while no significant adsorption was observed on other minerals (Ca, Mg, Zn, Cu and Ag). Results from this study suggest that all three types of NC, when incorporated in food or supplements as zero-calorie fiber, may affect food digestion and nutrient absorption.

Offline Solid-phase Extraction Large-volume Injection-Gas chromatography for the Analysis of Mineral Oil-saturated Hydrocarbons in Commercial Vegetable Oils.

An offline solid-phase extraction (SPE) approach combined with a large-volume injection (LVI)-gas chromatography-flame ionization detector (LVI-GC-FID) is improved for routine analysis of mineral oil saturated hydrocarbons (MOSH) in vegetable oils. The key procedure of the method consists in using offline SPE columns for MOSH purification. The SPE column packed with 1% Ag-activated silica gel was used to separate MOSH from triglycerides and olefins in variety of vegetable oils. The eluent of MOSH fraction was only 3 mL and the concentration step was quick with little evaporation loss. The limit of quantification (LOQ) of the method was 2.5 mg/kg and the linearity ranged from 2 to 300 mg/kg. The accuracy was assessed by measuring the recoveries from spiked oil samples and was higher than 90%. Twenty-seven commercial vegetable oils were analyzed, and different levels of MOSH contamination were detected with the highest being 259.4 mg/kg. The results suggested that it is necessary to routinely detect mineral oil contamination in vegetable oils for food safety.

Association between comorbidities and dementia in diabetes mellitus patients: population-based retrospective cohort study.

AIMS: Most diabetes mellitus (DM) patients have several comorbidities; the correlation of these comorbidities with dementia in DM requires clarification. METHODS: Using claims data from Taiwan National Health Insurance, we identified 33,709 DM adults before the year 2000 and randomly selected 67,066 non-DM patients matched by sex and age. Subjects were followed until diagnosis with dementia, excluded due to death/withdrawal from the insurance program, or followed until 2011. We compared the incidence and hazard ratio (HR) for dementia in both cohorts. RESULTS: Comorbidities were more prevalent in DM patients, including hypertension, hyperlipidemia, stroke, coronary artery and/or kidney disease. The HR was higher for the DM cohort with comorbidities than those without: 1.88 vs. 1.46 with hypertension; 1.56 vs. 1.39 with hyperlipidemia; 1.73 vs. 1.37 with coronary artery disease; 2.36 vs. 2.29 with stroke and 1.88 vs. 1.50 with kidney disease. The HR for dementia in diabetics rose from 1.41 in those without comorbidities to 2.49 in those with ≥4 comorbidities. In the DM cohort, HR was 1.22 for non-insulin-users and 1.41 for insulin-users, and 1.49 for type 1 DM and 1.23 for type 2 DM. CONCLUSION: Diabetic patients have an elevated risk of dementia, and comorbidity increases this risk.

[Authentication and adulteration analysis of sesame oil by FTIR spectroscopy].

It's common in edible oil market that adulterating low price oils in high price oils. Sesame oil was often adulterated because of its high quality and price, so the authentication and adulteration of sesame oil were qualitatively and quantitatively analyzed by Fourier transform infrared (FTIR) spectroscopy combined with chemometrics. Firstly, FTIR spectra of sesame oil, soybean oil, and sunflower seed oil in 4,000-650 cm(-1) were analyzed. It was very difficult to detect the difference among the spectra of above edible oils, because they are all mixtures of triglyceride fatty acids and have similar spectra. However, the FTIR data of edible oils in the fingerprint region of 1,800-650 cm(-1) differed slightly because their fatty acid compositions are different, so the data could be classified and recognized by chemometric methods. The authenticity model of sesame oil was built by principal component analysis (PCA) and soft independent modeling of class analogy (SIMCA). The recognition rate was 100%, and the built model was satisfactory. The classification limits of both soybean oil and sunflower seed oil adulterated in sesame oil were 10%, with the chemometric treatments of standard normal variation (SNV), partial least square (PLS) and PCA. In addition, the FTIR data processed by PCA and PLS were used to establish an analysis model of binary system of sesame oil mixed with soybean oil or sunflower oil, the prediction values had good corresponding relationship with true values, and the relative errors of prediction were between -6.87% and 8.07%, which means the quantitative model was practical. This method is very convenient and rapid after the models have been built, and can be used for rapid detection of authenticity and adulteration of sesame oil. The method is also practical and suitable for the daily analysis of large amount of samples.

[Observation on the therapeutic effect of electroacupuncture combined with small dose of clozapine in clinical treatment of refractory schizophrenia].

OBJECTIVE: To observe the effect of electroacupuncture (EA) in combination with small dose of clozapine on clinical symptoms of refractory schizophrenia patients so as to evaluate its validity and security. METHODS: Eighty schizophrenia patients were randomized into medication group and EA + medication group (n=40/group). Patients of medication group were treated with conventional oral administration of clozapine (50-100 mg/d to 200-500 mg/d, for 8 weeks) and those of EA + medication group treated by EA of Baihui(GV 20) and bilateral Taiyang (EX-HN 5) and oral administration of clozapine (50 mg/d to 100-150 mg/d). EA was given to the patients, 3 times a week for 8 weeks. Scores of the Positive and Negative Symptom Scale (PANSS) and the Untoward Effect Symptom Scale (TESS) were used to assess the therapeutic effect. RESULTS: Following treatment, PANSS scores for positive symptoms and the common psychiatric symptoms of the medication and EA + medication groups all decreased evidently from the 2rd week on (P < 0.05, P < 0.01), and those of the negative symptoms reduced obviously from the 4th week on (P < 0.05). Comparison between two groups showed no significant differences in PANSS scores for positive and negative symptoms and the common psychiatric symptoms after the treatment (P > 0.05). But TESS score of EA+ medication group was evidently lower than that of medication group (P < 0.01), suggesting an apparently fewer untoward effects in EA + medication group. Of the two 40 cases in medication and EA+ medication groups, 6 (15%) and 5 (12.5%) were cured, 8 and 8 (20%) experienced marked improvement in their symptoms, 17 (42.5%) and 16 (40%) had an improvement, 9 (22.5%) and 11 (27.5%) failed, with the effective rates being 77.5% and 72.5% separately. CONCLUSION: Both medication and EA+ medication can improve refractory schizophrenia patients'clinical symptoms, but the later has fewer untoward effects.

Baicalein is neuroprotective in rat MCAO model: role of 12/15-lipoxygenase, mitogen-activated protein kinase and cytosolic phospholipase A2.

Inflammatory damage and oxidative stress play an important role in cerebral ischemic pathogenesis and may represent a target for treatment. Baicalein, isolated from the traditional Chinese herbal medicine Huangqin, is an antioxidant and anti-inflammatory agent on one hand and a lipoxygenase inhibitor on the other hand. However, little is known regarding the mechanism of baicalein's neuroprotection in ischemic stroke. We therefore investigated the potential neuroprotective effects of baicalein and explored the underlying mechanisms. Male, Sprague-Dawley rats were subjected to permanent middle cerebral artery occlusion (MCAO) and baicalein was administered intravenously immediately after cerebral ischemia. At 24h after MCAO neurological deficit, brain water content and infarct sizes were measured. Immunohistochemistry, western blot and reverse transcription-polymerase chain reaction (RT-PCR) were used to analyse the expression of 12/15-lipoxygenase (12/15-LOX), p38 mitogen-activated protein kinase (p38 MAPK) and cytosolic phospholipase A2 (cPLA2) at gene and protein levels in ischemic brain cortex. The results showed that baicalein improved neurological deficit, reduced brain water content and infarct sizes, and downregulated the overexpression of 12/15-LOX, p38 MAPK and cPLA2 typically seen with MCAO. The results indicated that baicalein protected the brain from damage caused by MCAO, and this effect may be through downregulation of 12/15-LOX, p38 MAPK and cPLA2 expression.

The neuroprotective effects of Tanshinone IIA are associated with induced nuclear translocation of TORC1 and upregulated expression of TORC1, pCREB and BDNF in the acute stage of ischemic stroke.

The activation of cAMP response element binding protein (CREB) and transcription of CRE-targeted genes play critical roles in various physiological and pathological conditions. Transducers of regulated CREB activity (TORCs) represent a new family of conserved CREB coactivators that promote the activation of CRE-targeted genes. Tanshinone IIA (TSA) has been proven to protect the brain against focal ischemia injury. However, little is known regarding the underlying mechanisms. Herein, we examined the activity-dependent nuclear translocation of TORC1 (transducer of regulated CREB activity 1) and the expression of TORC1, phosphorylated CREB (pCREB) and BDNF (brain-derived neurotrophic factor) at the early time of ischemic stroke as well as after the treatment with TSA. We observed a bimodal increase in pCREB, TORC1 and BDNF protein levels and transient nuclear accumulation of TORC1 in the acute stage of ischemia. Compared with vehicle group, TSA (20mg/kg) dramatically lessened neurological deficits scores, brain water contents and infarct sizes, significantly enhanced nuclear accumulation of TORC1 and upregulated the expression of TORC1, pCREB and BDNF (P<0.05). Collectively, the present results suggest that TSA protects rat brain from pristine ischemic damage in cerebral cortex, which might be correlated with induced nuclear translocation of TORC1 and upregulated expression of TORC1, pCREB and BDNF.

Neuroprotection of early and short-time applying atorvastatin in the acute phase of cerebral ischemia: down-regulated 12/15-LOX, p38MAPK and cPLA2 expression, ameliorated BBB permeability.

BACKGROUND: It has been proved that chronic administration and pre-treatment with atorvastatin could protect brain tissue against ischemic injury. However, little is known regarding the effect of atorvastatin in the acute phase of ischemic stroke. This study investigated the potential neuroprotective effects of atorvastatin and underlying mechanisms in vivo. METHODS: Male Sprague-Dawley rats were subjected to permanent middle cerebral artery occlusion (MCAO). Experiment 1 was used to evaluate time course expressions of 12/15-LOX, mitogen-activated protein kinase (MAPK), phosphorylated-p38MAPK (phospho-p38MAPK) and cytosolic phospholipase A2 (cPLA2) after cerebral ischemia, seven time points were included. Experiment 2 was used to detect atorvastatin's neuroprotection in the acute phase of ischemic stroke; atorvastatin was administered immediately after MCAO. Neurological deficit, brain water content and infarct size were measured at 24h after stoke. Immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were used to analyze the expression of 12/15-LOX, p38MAPK, phospho-p38MAPK and cPLA2. Experiment 3 was used to detect atorvastatin's influence on blood-brain barrier (BBB). RESULTS: 12/15-LOX, p38MAPK, phospho-p38MAPK and cPLA2 were up-regulated after cerebral ischemia. Compared with MCAO group, atorvastatin dramatically reduced brain water content and infarct sizes, and the over-expressions of 12/15-LOX, p38MAPK, phospho-p38MAPK and cPLA2 were significantly decreased in high dose group (20mg/kg, P<0.05). Meanwhile, extra-vascular IgG was not only reduced, but BBB permeability was also ameliorated. CONCLUSIONS: Atorvastatin protected brain from damage caused by MCAO at the early stage; this effect may be through down-regulation of 12/15-LOX, p38MAPK and cPLA2 expressions, and ameliorating BBB permeability.