iridoids has been researched along with Reperfusion-Injury* in 32 studies
1 review(s) available for iridoids and Reperfusion-Injury
1 trial(s) available for iridoids and Reperfusion-Injury
31 other study(ies) available for iridoids and Reperfusion-Injury
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Loganin exerts a protective effect on ischemia-reperfusion-induced acute kidney injury by regulating JAK2/STAT3 and Nrf2/HO-1 signaling pathways.
To investigate the role of loganin in hypoxia/reperfusion (H/R)-induced renal tubular epithelial cells and ischemia/reperfusion-induced acute kidney injury (AKI). Cells were received H/R treatment and cultured with different concentrations of loganin. The cell activity and apoptosis were detected. The expressions of apoptosis-related proteins, inflammatory factors, oxidative stress related molecules, and related molecules of JAK2/STAT3 and Nrf2/HO-1 signaling pathways were measured. AKI model of mice was established by I/R procedure, and the kidney was collected for hematoxylin and eosin (HE) staining. H/R treatment inhibited cell activity and apoptosis, but loganin attenuated the effect of H/R. Moreover, loganin inhibited H/R-induced inflammatory response and oxidative stress in tubular epithelial cells. Loganin down-regulated the expression of apoptosis-related proteins, suppressed JAK2/STAT3 pathway, and activated Nrf2/HO-1 pathway. In animal experiment, loganin reduced tubular injury in AKI mice.Loganin had anti-apoptotic, anti-inflammatory, and anti-oxidative stress effects on H/R-induced tubular epithelial cells, and could improve AKI in mice induced by I/R. This effect might be achieved by inhibiting JAK2/STAT3 and activating the Nrf2/HO-1 signaling pathway. Topics: Acute Kidney Injury; Animals; Apoptosis; Heme Oxygenase-1; Iridoids; Ischemia; Kidney; Mice; NF-E2-Related Factor 2; Oxidative Stress; Reperfusion; Reperfusion Injury; Signal Transduction | 2022 |
Geniposide-Loaded Liposomes for Brain Targeting: Development, Evaluation, and In Vivo Studies.
Geniposide (GE) possesses excellent neuroprotective effects but with poor brain targeting and short half-life. Liposome was considered to have great potential for brain diseases. Therefore, this research aimed to develop a geniposide liposome (GE-LP) as a brain delivery system for cerebral ischemia reperfusion injury (CIRI) therapy and evaluate its characterization, pharmacokinetics, brain targeting, and neuroprotective effects in vivo. Then, a reverse-phase evaporation method was applied to develop the GE-LP and optimize the formulation. Notably, the GE-LP had suitable size, which was 223.8 nm. Subsequently, the pharmacokinetic behavior of GE solution and GE-LP in mice plasma was investigated, and the brain targeting was also researched. The results showed that GE in plasma of GE-LP displayed three folds longer distribution half-life and a higher bioavailability and brain targeting compared to GE solution. In vivo neuroprotective effects was evaluated through the middle cerebral artery occlusion (MCAO) rat model, and GE-LP exhibited a stronger tendency in preventing the injury of CIRI, which can significantly improve neurological deficits. Overall, this study demonstrates GE-LP as a new formulation with ease of preparation, sustained release, and high brain targeting, which has significant development prospects on CIRI; this is expected to improve the efficacy of GE and reduce the frequency of administration. Topics: Animals; Brain; Iridoids; Liposomes; Mice; Rats; Rats, Sprague-Dawley; Reperfusion Injury | 2021 |
Effect of oleuropein on oxidative stress, inflammation and apoptosis induced by ischemia-reperfusion injury in rat kidney.
This study aimed to evaluate the effect of oleuropein (OLE), the main phenolic compound present in olive leaves, on kidney ischemia-reperfusion injury (IRI) and to explore the underlying protective mechanism.. Rat kidneys were subjected to 60 min of bilateral warm ischemia followed by 120 min of reperfusion. OLE was administered orally 48 h, 24 h and 30 min prior to ischemia at doses of 10, 50 and 100 mg/kg body weight. The creatinine, urea, uric acid concentrations and lactate dehydrogenase (LDH) activity in plasma were evaluated. Oxidative stress and inflammation parameters were also assessed. Renal expression of AMP-activated protein kinase (p-AMPK), endothelial nitric oxide synthase (eNOS), mitogen-activated protein kinases (MAPK), inflammatory proteins and apoptotic proteins were evaluated using Western blot.. Our results showed that OLE at 50 mg/kg reduced kidney IRI as revealed by a significant decrease of plasmatic creatinine, urea, uric acid concentrations and LDH activity. In parallel, OLE up-regulated antioxidant capacities. Moreover, OLE diminished the level of CRP and the expression of cyclooxygenase 2 (COX-2). Finally, OLE enhanced AMPK phosphorylation as well as eNOS expression whereas MAPK, and cleaved caspase-3 implicated in cellular apoptosis were attenuated in the ischemic kidneys.. In conclusion, this study shows that OLE could be used as therapeutic agent to reduce IRI through its anti-oxidative, anti-inflammatory and anti-apoptotic properties. Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Apoptosis; Dose-Response Relationship, Drug; Inflammation; Iridoid Glucosides; Iridoids; Kidney; Male; Oxidative Stress; Rats; Rats, Wistar; Reperfusion Injury; Time Factors | 2020 |
Genipin protects against cerebral ischemia-reperfusion injury by regulating the UCP2-SIRT3 signaling pathway.
Topics: Animals; Apoptosis; Energy Metabolism; Iridoids; Male; Mice; Mice, Inbred C57BL; Mitochondria; Neuroprotective Agents; Oxidative Stress; Reactive Oxygen Species; Reperfusion Injury; Signal Transduction; Sirtuin 3; Stroke; Uncoupling Protein 2 | 2019 |
Geniposide protects against hypoxia/reperfusion-induced blood-brain barrier impairment by increasing tight junction protein expression and decreasing inflammation, oxidative stress, and apoptosis in an in vitro system.
The blood-brain barrier (BBB) is involved in the pathogeneses of ischemic stroke (IS). Geniposide (GEN), an iridoid glycoside isolated from Gardenia jasminoides Ellis, has been used for the treatment of IS. However, the effects of GEN on the BBB are poorly understood. In vitro disease models of the BBB could be very helpful for the elucidation of underlying mechanisms and the development of novel therapeutic strategies. Therefore, we established an in vitro BBB model composed of primary cultures of brain microvascular endothelial cells and astrocytes. We then used this in vitro model to investigate the effect of GEN on the function of the BBB. Oxygen glucose deprivation and reoxygenation (OGD/R) significantly increased permeability and cell apoptosis in this in vitro BBB model. Notably, GEN pretreatment effectively improved the BBB function by decreasing the permeability of the BBB, promoting expression of tight junction proteins (zonula occludens-1, claudin-5, and occludin) and gamma-glutamyl transpeptidase, increasing transendothelial electrical resistance, mitigating oxidative stress damage and the release of inflammatory cytokines, downregulating the expression levels of matrix metallopeptidases-9 (MMP-9) and MMP-2, and increasing the release of brain derived neurotrophic factor and glial cell derived neurotrophic factor. Therefore, GEN can ameliorate the BBB dysfunction induced by OGD/R conditions through multiple protective mechanisms. The findings suggest that GEN may be an appropriate drug for restoring the barrier function of the BBB. Topics: Animals; Apoptosis; Blood-Brain Barrier; Cell Hypoxia; Cytoprotection; Iridoids; Nerve Growth Factors; Oxidative Stress; Oxygen; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Tight Junction Proteins | 2019 |
Low-Dose 4-Hydroxy-2-Nonenal (HNE) Reperfusion Therapy Displays Cardioprotective Effects in Mice After Myocardial Infarction That Are Abrogated by Genipin.
BACKGROUND Revascularization is a successful therapeutic strategy for myocardial infarction. However, restoring coronary blood flow can lead to ischemia-reperfusion (I/R) injury. Low-dose 4-hydroxy-2-nonenal (HNE) therapy appears to play a key role in myocardial tolerance to I/R injury. We hypothesized that the positive effects of HNE on myocardial I/R injury may be UCP3-dependent. MATERIAL AND METHODS Adult male wild-type (WT) or UCP3 knockout (UCP3-/-) mice were pre-treated with the UCP inhibitor genipin or saline 1 h before ischemia and underwent 30-min coronary artery ligation followed by 24-h reperfusion. Mice were treated with intravenous HNE (4 mg/kg) or saline 5 min before reperfusion. Echocardiography was conducted to measure left ventricular end-diastolic posterior wall thickness (LVPWd), end-diastolic diameter (LVEDD), and fractional shortening (FS). Infarct size was measured by TTC staining. qRT-PCR and Western blotting were used to assess the expression of UCP3, UCP2, and the apoptosis markers cytochrome C and cleaved caspase-3. RESULTS HNE improved survival at 24 h post-MI in wild-type mice (p<0.05) but not in UCP3-/- mice. HNE preserved LVEDD and FS in WT mice (p<0.05) but not in UCP3-/- mice. HNE reduced infarct size in WT mice (p<0.05) but not in UCP3-/- mice. HNE upregulated UCP3 expression (p<0.05) but did not affect UCP2 expression. HNE reduced apoptosis marker expression in WT mice (p<0.05) but not in UCP3-/- mice. HNE's positive effects were abrogated by genipin in an UCP3-dependent manner. CONCLUSIONS Low-dose HNE reperfusion therapy attenuates murine myocardial I/R injury in an UCP3-dependent manner. These effects are abrogated by genipin in an UCP3-dependent manner. Topics: Aldehydes; Animals; Apoptosis; Coronary Vessels; Heart; Iridoids; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Myocardial Infarction; Myocardial Reperfusion; Myocardial Reperfusion Injury; Myocardium; Reperfusion Injury; Uncoupling Protein 3 | 2018 |
Gene Expression Profiling Confirms the Dosage-Dependent Additive Neuroprotective Effects of Jasminoidin in a Mouse Model of Ischemia-Reperfusion Injury.
Recent evidence demonstrates that a double dose of Jasminoidin (2·JA) is more effective than Jasminoidin (JA) in cerebral ischemia therapy, but its dosage-effect mechanisms are unclear. In this study, the software GeneGo MetaCore was used to perform pathway analysis of the differentially expressed genes obtained in microarrays of mice belonging to four groups (Sham, Vehicle, JA, and 2·JA), aiming to elucidate differences in JA and 2·JA's dose-dependent pharmacological mechanism from a system's perspective. The top 10 enriched pathways in the 2·JA condition were mainly involved in neuroprotection (70% of the pathways), apoptosis and survival (40%), and anti-inflammation (20%), while JA induced pathways were mainly involved in apoptosis and survival (60%), anti-inflammation (20%), and lipid metabolism (20%). Regarding shared pathways and processes, 3, 1, and 3 pathways overlapped between the Vehicle and JA, Vehicle and 2·JA, and JA and 2·JA conditions, respectively; for the top ten overlapped processes these numbers were 3, 0, and 4, respectively. The common pathways and processes in the 2·JA condition included differentially expressed genes significantly different from those in JA. Seven representative pathways were only activated by 2·JA, such as Topics: Animals; Cerebrovascular Disorders; Disease Models, Animal; Dose-Response Relationship, Drug; Gene Expression Profiling; Gene Expression Regulation; Humans; Iridoids; Male; Mice; Reperfusion Injury | 2018 |
Protective Effects of Oleuropein Against Cerebral Ischemia/Reperfusion by Inhibiting Neuronal Apoptosis.
BACKGROUND In this study, we investigated the potential neuroprotective effect of oleuropein (OLE) on apoptotic changes via modulating Akt/glycogen synthase kinase 3 beta (Akt/GSK-3b) signaling in a rat model of cerebral ischemia/reperfusion injury (IRI). MATERIAL AND METHODS Sprague-Dawley male rats (12 weeks, n=200) were randomly assigned to 5 groups: sham group, vehicle (IRI+ vehicle) group, OLE (IRI+OLE) group, OLE+LY294002 (IRI+OLE+LY294002) group, and LY294002(IRI+LY294002) group. The rats were subjected to cerebral ischemia/reperfusion injury (IRI) model and treated once daily for 5 days with vehicle and OLE (100 mg/kg via intraperitoneal injection) after IRI injury. LY294002 (0.3 mg/kg) was intraperitoneally injected once at 30 min after IRI injury. Brain edema, neurological deficit, rotarod latencies, and Morris water maze (MWM) performance were evaluated after IRI. The number of dead cells were assayed by TUNEL staining. Western blot was used to detect the expression of Bcl-2, Bax, cleaved caspase-3 (CC3), neurotrophic factors, and the phosphorylation levels of Akt and GSK-3β. RESULTS Compared with the vehicle group, brain water content, neurological deficits, rotarod latencies, and escape latency following IRI were reduced in the OLE group. Cell apoptosis and reduced neurotrophic factor caused by IRI was also attenuated by OLE. Furthermore, increased p-Akt and decreased p-GSK-3β were caused by OLE, which were associated with decrease of Bax/Bcl-2 ratio and the suppression of Caspase-3 activity after IRI. Importantly, all the beneficial effects of OLE in the vehicle group were abrogated by PI3K inhibitor LY294002. CONCLUSIONS Cerebral ischemia was protected by OLE via suppressing apoptosis through the Akt/GSK-3β pathway and upregulating neurotrophic factor after IRI. Topics: Animals; Apoptosis; Brain; Brain Ischemia; Disease Models, Animal; Glycogen Synthase Kinase 3 beta; Infarction, Middle Cerebral Artery; Iridoid Glucosides; Iridoids; Male; Neurons; Neuroprotective Agents; Oncogene Protein v-akt; Phosphatidylinositol 3-Kinases; Phosphorylation; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Signal Transduction | 2018 |
Poly-dimensional network comparative analysis reveals the pure pharmacological mechanism of baicalin in the targeted network of mouse cerebral ischemia.
This study aimed to investigate the pure pharmacological mechanisms of baicalin/baicalein (BA) in the targeted network of mouse cerebral ischemia using a poly-dimensional network comparative analysis.. Eighty mice with induced focal cerebral ischemia were randomly divided into four groups: BA, Concha Margaritifera (CM), vehicle and sham group. A poly-dimensional comparative analysis of the expression levels of 374 stroke-related genes in each of the four groups was performed using MetaCore.. BA significantly reduced the ischemic infarct volume (P<0.05), whereas CM was ineffective. Two processes and 10 network nodes were shared between "BA vs CM" and vehicle, but there were no overlapping pathways. Two pathways, three processes and 12 network nodes overlapped in "BA vs CM" and BA. The pure pharmacological mechanism of BA resulted in targeting of pathways related to development, G-protein signaling, apoptosis, signal transduction and immunity. The biological processes affected by BA were primarily found to correlate with apoptotic, anti-apoptotic and neurophysiological processes. Three network nodes changed from up-regulation to down-regulation, while mitogen-activated protein kinase kinase 6 (MAP2K6, also known as MEK6) changed from down-regulation to up-regulation in "BA vs CM" and vehicle. The changed nodes were all related to cell death and development.. The pure pharmacological mechanism of BA is related to immunity, apoptosis, development, cytoskeletal remodeling, transduction and neurophysiology, as ascertained using a poly-dimensional network comparative analysis. Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cerebral Infarction; Disease Models, Animal; Down-Regulation; Drugs, Chinese Herbal; Flavonoids; Gene Expression Profiling; Iridoids; Mice; Reperfusion Injury; Signal Transduction | 2017 |
Genipin protects the liver from ischemia/reperfusion injury by modulating mitochondrial quality control.
Hepatic ischemia and reperfusion (IR) injury is closely linked to oxidative mitochondrial damage. Since mitochondrial quality control (QC) plays a pivotal role in the recovery of impaired mitochondrial function, mitochondrial QC has emerged as a potential therapeutic target. Genipin, an iridoid compound from Gardenia jasminoides, has been showed antioxidant and anti-inflammatory properties. In this study, we investigated the hepatoprotective mechanism of genipin against IR-induced hepatic injury, particularly focusing on mitochondrial QC. Male C57BL/6 mice underwent liver ischemia for 60min, followed by reperfusion for 6h. Genipin (100mg/kg, i.p.) or vehicle (10% Tween 80 in saline) was administrated to mice 1h before ischemia. Liver and blood samples were collected 6h after reperfusion. Hepatic IR increased hepatocellular oxidative damage and induced mitochondrial dysfunction. These phenomena were ameliorated by genipin. Hepatic IR also increased the level of mitochondrial fission, such as dynamin-related protein 1 and the level of PINK1 protein expression. In contrast, hepatic IR decreased the levels of mitochondrial biogenesis related proteins (e.g., peroxisome proliferator-activated receptor gamma coactivator 1α, nuclear respiratory factor 1, and mitochondrial transcription factor A), mitophagy related proteins (e.g., Parkin), and fusion related protein (e.g., mitofusin 2). Furthermore, hepatic IR decreased the levels of sirtuin1 protein and phosphorylation of AMP-activated protein kinase. Genipin alleviated these IR-induced changes. These data indicate that genipin protects against IR-induced hepatic injury via regulating mitochondrial QC. (225/250). Topics: AMP-Activated Protein Kinases; Animals; Cytokines; Gardenia; Iridoids; Lipid Peroxidation; Liver Diseases; Male; Mice; Mice, Inbred C57BL; Mitochondria, Liver; Mitochondrial Swelling; Oxidative Stress; Protective Agents; Quality Control; Reperfusion Injury; Signal Transduction; Sirtuin 1 | 2017 |
Variation of pathways and network profiles reveals the differential pharmacological mechanisms of each effective component to treat middle cerebral artery ischemia-reperfusion mice.
Using a system pharmacology strategy, this study evaluated the unique pharmacological characteristics of three different neuroprotective compounds for the treatment of cerebral ischemia-reperfusion. A microarray including 374 brain ischemia-related genes was used to identify the differentially expressed genes among five treatment groups: baicalin, jasminoidin, ursodeoxycholic acid, sham, and vehicle, and MetaCore analysis software was applied to identify the significantly altered pathways, processes and interaction network parameters. At pathway level, 46, 25, and 31 pathways were activated in the baicalin, jasminoidin, and ursodeoxycholic acid groups, respectively. Thirteen pathways mainly related with apoptosis and development were commonly altered in the three groups. Additionally, baicalin also targeted pathways related with development, neurophysiologic process and cytoskeleton remodeling, while jasminoidin targeted pathways related with cell cycle and ursodeoxycholic acid targeted those related with apoptosis and development. At process level, three processes were commonly regulated by the three groups in the top 10 processes. Further interaction network analysis revealed that baicalin, jasminoidin, and ursodeoxycholic acid displayed unique features either on network topological parameters or network structure. Additional overlapping analysis demonstrated that compared with ursodeoxycholic acid, the pharmacological mechanism of baicalin was more similar with that of jasminoidin in treating brain ischemia. The data presented in this study may contribute toward the understanding of the common and differential pharmacological mechanisms of these three compounds. Topics: Animals; Flavonoids; Gene Expression Profiling; Gene Regulatory Networks; Iridoids; Ischemia; Male; Metabolic Networks and Pathways; Mice; Microarray Analysis; Middle Cerebral Artery; Neuroprotective Agents; Reperfusion Injury; Ursodeoxycholic Acid | 2016 |
Restoration of Opa1-long isoform inhibits retinal injury-induced neurodegeneration.
Optic atrophy 1 (Opa1) is a critical factor that regulates fusion and other important functions of mitochondria. In mitochondrion, the N-terminal mitochondrial targeting sequence of Opa1 precursors is removed to generate Opa1 long isoforms (L-Opa1), which are further cleaved into short isoforms (S-Opa1). In the present study, we found that retinal ischemia-reperfusion (I/R) injury and intravitreal injection of carbonylcyanide m-chlorophenyl hydrazone (CCCP) both dramatically induced Opa1 cleavage and caused loss of L-Opa1. In cultured neuronal cells under hypoxia-reoxygenation (H/R) injury, similar changes for Opa1 were also observed. In contrast, restoration of L-Opa1 level by overexpression of S1 cleavage site deletion Opa1 splice 1 (Opa1-ΔS1) not only normalized the H/R-induced mitochondrial morphology changes, but also inhibited the H/R-induced apoptosis, necrosis, and the intracellular ATP loss. Furthermore, recovering L-Opa1 level in the I/R-injured retina by intravitreal injection of genipin or overexpression of Opa1-ΔS1 inhibited apoptosis, necrosis, cell loss in the ganglion cell layer and retinal thickness reduction. Together, our data demonstrated the loss of L-Opa1 is involved in the development of retinal I/R injury, indicating restoring L-Opa1 level may be considered as a therapeutic target for I/R injury-related diseases, at least for the retina. Key messages: Retinal ischemia-reperfusion (I/R) or hypoxia-reoxygenation (H/R) injury induces L-Opa1 loss. Opa1-ΔS1 overexpression inhibits H/R-induced L-Opa1 loss. Opa1-ΔS1 overexpression inhibits H/R-induced mitochondria morphology change. Opa1-ΔS1 and genipin inhibit retinal I/R injury-induced necroptosis. Opa1-ΔS1 and genipin inhibit retinal I/R injury-induced neurodegeneration. Topics: Animals; Apoptosis; Cell Death; Cell Line; GTP Phosphohydrolases; Humans; Iridoids; Male; Mitochondria; Protein Isoforms; Rats, Wistar; Reperfusion Injury; Retina; Retinal Neurons | 2016 |
Oleuropein, a natural extract from plants, offers neuroprotection in focal cerebral ischemia/reperfusion injury in mice.
Oleuropein (OLE) was found to have anti-inflammatory and anti-oxidant effects. The latest study has shown that it can resist myocardial injury that follows an acute myocardial infarction and can rescue impaired spinal nerve cells. In this study, we investigated the neuroprotective effects of OLE on cerebral ischemia and reperfusion injury in a middle cerebral artery occlusion model in mice.OLE (100 mg/kg) was injected intraperitoneally 1h before ischemia. We found that the volume of cerebral infarction was significantly reduced after 75 min of ischemia and 24 h of reperfusion compared with the I/R (ischemia/reperfusion) group. This protective function occurred in a dose-dependent manner. We also found that treatment with OLE could reduce the cerebral infarct volume. The neuroprotective effect was prolonged from 2 h to 4 h when we injected OLE intracerebroventricularly after reperfusion. We then found that OLE can decrease the level of cleavedcaspase-3, an important marker of apoptosis, in the ischemic mouse brain. Finally, we explored the role of OLE in providing anti-apoptotic effects through the increased expression of Bcl-2 and the decreased expression of Bax, which are important markers in apoptosis. As shown above, the function and safety of OLE in cardiovascular disease may indicate that it is a potential therapeutic for stroke. Topics: Animals; Apoptosis; bcl-2-Associated X Protein; Brain; Caspase 3; Infarction, Middle Cerebral Artery; Iridoid Glucosides; Iridoids; Male; Mice, Inbred ICR; Neurons; Neuroprotection; Neuroprotective Agents; Olea; Plant Extracts; Plant Leaves; Proto-Oncogene Proteins c-bcl-2; Reperfusion Injury | 2016 |
Vertical and Horizontal Convergences of Targeting Pathways in Combination Therapy with Baicalin and Jasminoidin for Cerebral Ischemia.
Baicalin (BA) and jasminoidin (JA) exert an additive effect in the treatment of cerebral ischemia, but the underlying molecular mechanism is still unclear. One hundred mice with focal cerebral ischemia/re-perfusion injury were divided into 5 groups: BA, JA, combination therapy (BJ), sham and vehicle. The differentially expressed genes identified by microarray consisting of 374 cDNAs were uploaded into GeneGo MetaCore software for pathway analyses. Networks were constructed to visualize the interactions of the differentially expressed genes. Among the top ten pathways and processes, we found 5, 3, 2 overlapping pathways and 6, 4, 6 overlapping processes between the BA and JA, BA and BJ, JA and BJ groups, respectively; of which 1 pathway and 3 processes were shared by all the three groups. Six representative pathways and 3 processes were activated only in BJ, such as Gamma-secretase proteolytic targets,etc. These BJ representative targeting pathways showed both vertical (e.g. Cytoplasmic/mitochondrial transport of proapoptotic Bid Bmf and Bim) and horizontal (e.g. Endothelin-1/EDNRA signaling) convergences with those of the BA and JA groups based on the upstream and downstream relationship of cerebral ischemia network, which may help to reveal their additive mechanism in the treatment of cerebral ischemia. Network comparison identified important transcription factors that regulated some of the other BJ related genes, such as cMyb and NF-AT. Such a systemic approach based on multiple pathways and networks may provide a robust path to understand the complex pharmacological variations of combination therapies. Topics: Animals; Brain Ischemia; Disease Models, Animal; Drug Evaluation, Preclinical; Drug Therapy, Combination; Flavonoids; Gene Expression; Iridoids; Male; Mice; Microarray Analysis; Random Allocation; Reperfusion Injury | 2016 |
The components of Huang-Lian-Jie-Du-Decoction act synergistically to exert protective effects in a rat ischemic stroke model.
Huang-Lian-Jie-Du-Decoction (HLJDD, Oren-gedoku-to in Japanese) is commonly used in traditional Chinese medicine (TCM) to treat ischemic stroke. This study investigated the efficacy of various combinations of the major components of HLJDD, berberine (A), baicalin (B), and jasminoidin (C), on the treatment of ischemic stroke modeled by middle cerebral artery occlusion (MCAO) in rats. The effects of A, B and C individually and their combinations were investigated using proton nuclear magnetic resonance (1H NMR)-based metabolomics complemented with neurologic deficit scoring, infarct volume measurement, biochemistry, histopathology and immunohistochemistry, as well as quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting. Ischemic stroke produces severe oxidative stress, which induces further damage. Our results show that the ABC combination treatment increased levels of cellular antioxidants that scavenged reactive oxygen species during ischemia-reperfusion via the nuclear erythroid 2-related factor 2 (Nrf2) signaling cascade. These protective effects were not observed with the other treatments. These results suggest that a combination of component herbs in HLJDD exhibit stronger effects than the individual herbs alone. Our integrated metabolomics approach also provides a tractable, powerful tool for understanding the science behind TCM formulations. Topics: Animals; Berberine; Brain; Disease Models, Animal; Drug Synergism; Drugs, Chinese Herbal; Flavonoids; Free Radical Scavengers; Infarction, Middle Cerebral Artery; Iridoids; Male; Metabolomics; Neuroprotective Agents; NF-E2-Related Factor 2; Oxidative Stress; Phytotherapy; Plants, Medicinal; Proton Magnetic Resonance Spectroscopy; Rats, Sprague-Dawley; Reperfusion Injury | 2016 |
Effects of oleuropein and pinoresinol on microvascular damage induced by hypoperfusion and reperfusion in rat pial circulation.
The present study was aimed to assess the in vivo acute effects of oleuropein or/and pinoresinol, polyphenols widely diffused in natural sources, on rat pial microvascular responses during transient BCCAO and reperfusion.. Rat pial microcirculation was visualized by fluorescence microscopy through a closed cranial window. Pial arterioles were classified into five orders of branching. Capillaries were assigned order 0, the smallest arterioles order 1 and the largest ones order 5.. Rats subjected to BCCAO and reperfusion showed: arteriolar diameter decrease, microvascular leakage, leukocyte adhesion in venules, and reduction in capillary perfusion. Pretreatment with oleuropein or pinoresinol, a higher dose before BCCAO determined dilation in all arteriolar orders RE. Microvascular leakage was reduced as well as leukocyte adhesion and ROS formation, while capillary perfusion was protected. Inhibition of endothelium nitric oxide synthase prior to oleuropein or pinoresinol reduced the effect of these polyphenols on pial arteriolar diameter and leakage. These substances, administered together, prevented microvascular damage to a larger extent.. Oleuropein and pinoresinol were both able to protect pial microcirculation from I-reperfusion injury, to increase nitric oxide release and to reduce oxidative stress preserving pial blood flow distribution. Topics: Animals; Arterioles; Brain Injuries; Cerebrovascular Circulation; Furans; Iridoid Glucosides; Iridoids; Lignans; Male; Microcirculation; Rats; Rats, Wistar; Reperfusion Injury; Vasodilator Agents | 2015 |
[Screening of Active Fractions from Huanglian Jiedu Decoction against Primary Neuron Injury after Oxygen-Glucose Deprivation].
To observe the protective effect of active fractions of Huanglian Jiedu Decoction (HJD) on primary cortical neuron injury after oxygen-glucose deprivation (OGD)/reperfusion (R) injury. Methods Using macroporous resin method, HJDFE30, HJDFE50, HJDFE75, and HJDFE95 with 30%, 50%, 75%, and 95% alcohol were respectively prepared. Then the content of active components in different HJD fractions was determined with reverse phase high-performance liquid chromatography (RP-HPLC). The OGD/R injury model was induced by sodium dithionite on primary cortical neurons in neonate rats. MTT assay was used to observe the effect of four fractions (HJDFE30, HJDFE50, HJDFE75, and HJDFE95) and seven index components of HJD on the neuron viability.. RP-HPLC showed active component(s) contained in HJDFE30 was geniposide; baicalin, palmatine, berberine, and wogonside contained in HJDFE50; baicalin, berberine, baicalein, and wogonin contained in HJDFE75. The neuron viability was decreased after OGD for 20 min and reperfusion for 1 h, (P <0. 01), and significantly increased after administered with HJD, HJDFE30, HJDFE50, and HJDFE75 (P <0. 05, P <0. 01). Geniposide, baicalin, baicalein, palmatine, wogonside, and wogonin could increase the cortical neuron viability (P <0. 05, P <0. 01).. HJDFE30, HJDFE50, and HJDFE75, as active fractions of HJD, had protective effect on primary cortical neuron injury after OGD/R. Furthermore, geniposide, baicalin, and baicalein were main active components of HJD. Topics: Animals; Berberine; Berberine Alkaloids; Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Flavanones; Flavonoids; Glucose; Iridoids; Models, Animal; Neurons; Oxygen; Rats; Reperfusion Injury | 2015 |
Convergent and divergent pathways decoding hierarchical additive mechanisms in treating cerebral ischemia-reperfusion injury.
Cerebral ischemia is considered to be a highly complex disease resulting from the complicated interplay of multiple pathways. Disappointedly, most of the previous studies were limited to a single gene or a single pathway. The extent to which all involved pathways are translated into fusing mechanisms of a combination therapy is of fundamental importance.. We report an integrative strategy to reveal the additive mechanism that a combination (BJ) of compound baicalin (BA) and jasminoidin (JA) fights against cerebral ischemia based on variation of pathways and functional communities.. We identified six pathways of BJ group that shared diverse additive index from 0.09 to 1, which assembled broad cross talks from seven pathways of BA and 16 pathways of JA both at horizontal and vertical levels. Besides a total of 60 overlapping functions as a robust integration background among the three groups based on significantly differential subnetworks, additive mechanism with strong confidence by networks altered functions.. These results provide strong evidence that the additive mechanism is more complex than previously appreciated, and an integrative analysis of pathways may suggest an important paradigm for revealing pharmacological mechanisms underlying drug combinations. Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Disease Models, Animal; Drug Therapy, Combination; Drugs, Chinese Herbal; Flavonoids; Infarction, Middle Cerebral Artery; Iridoids; Male; Mice; Mice, Inbred Strains; Microarray Analysis; Molecular Sequence Data; Principal Component Analysis; Reperfusion Injury; Signal Transduction | 2014 |
A partial pathway- and network-based transformation reveals the synergistic mechanism of JA and UA against cerebral ischemia-reperfusion injury.
Topics: Animals; Brain; Brain Ischemia; Drug Synergism; Gene Regulatory Networks; Iridoids; Linear Models; Male; Mice; Models, Genetic; Oligonucleotide Array Sequence Analysis; Reperfusion Injury; Signal Transduction; Transcriptome; Ursodeoxycholic Acid | 2014 |
Effects of a polyphenol present in olive oil, oleuropein aglycone, in a murine model of intestinal ischemia/reperfusion injury.
Dietary olive oil supplementation and more recently, olive oil phenols have been recommended as important therapeutic interventions in preventive medicine. Ole has several pharmacological properties, including antioxidant, anti-inflammatory, antiatherogenic, anticancer, antimicrobial, and antiviral and for these reasons, is becoming an important subject of study in recent years. The aim of this study was to investigate the effects of Ole aglycone on the modulation of the secondary events in mice subjected to intestinal IRI. This was induced in mice by clamping the superior mesenteric artery and the celiac trunk for 30 min, followed by release of the clamp, allowing reperfusion for 1 h. After 60 min of reperfusion, animals were killed for histological examination of the ileum tissue and immunohistochemical localization of proinflammatory cytokines (TNF-α and IL-1β) and adhesion molecules (ICAM-1 and P-sel); moreover, by Western blot analysis, we investigated the activation of NF-κB and IκBα. In addition, we evaluated the apoptosis process, as shown by TUNEL staining and Bax/Bcl-2 expressions. The results obtained by the histological and molecular examinations showed in Ole aglycone-treated mice, a decrease of inflammation and apoptosis pathway versus SAO-shocked mice. In conclusion, we propose that the olive oil compounds, in particular, the Ole aglycone, could represent a possible treatment against secondary events of intestinal IRI. Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Apoptosis; Blotting, Western; Cell Adhesion Molecules; Cytokines; Disease Models, Animal; Immunohistochemistry; In Situ Nick-End Labeling; Intestinal Diseases; Iridoid Glucosides; Iridoids; Male; Mice; Olive Oil; Plant Oils; Polyphenols; Pyrans; Reperfusion Injury | 2013 |
Variations in target gene expression and pathway profiles in the mouse hippocampus following treatment with different effective compounds for ischemia-reperfusion injury.
In order to elucidate the overlapping and diverse pharmacological protective mechanisms of different Chinese medicinal compounds, we investigated the alteration of gene expression and activation of signaling pathways in the mouse hippocampus after treatment of cerebral ischemia-reperfusion injury with various compounds. A microarray including 16,463 genes was used to identify differentially expressed genes among six treatment groups: baicalin (BA), jasminoidin (JA), cholic acid (CA), concha margaritiferausta (CM), sham, and vehicle. The US Food and Drug Administration (FDA) ArrayTrack system and Kyoto Encyclopedia of Genes and Genomes (KEGG) database were used to screen significantly altered genes and pathways (P < 0.05, fold change >1.5). Vehicle treatment alone resulted in alteration of 726 genes (283 upregulated, 443 downregulated) compared to the sham treatment group. BA, JA, and CA treatments, but not CM treatment, were effective in reducing infarct volume compared with vehicle treatment (P < 0.05). Compared with the CM group, a total of 167 (73 upregulated, 94 downregulated), 379 (211 upregulated, 168 downregulated), and 181 (76 upregulated, 105 downregulated) altered genes were found in the BA, JA, and CA groups, respectively. The numbers of overlapping genes between the BA and JA, BA and CA, and JA and CA groups were 28 (16 upregulated, 12 downregulated), 14 (4 upregulated, 10 downregulated), and 31 (8 upregulated, 23 downregulated), respectively. Three overlapping genes were identified among the BA, JA, and CA treatment groups: Il1rap, Gnb5, and Wdr38. Based on KEGG pathway analysis, two, seven, and four pathways were significantly activated in the BA, JA, and CA groups, respectively, when compared to the CM group. The ATP-binding cassette (ABC) transporters general pathway was activated by BA and JA treatment, and the mitogen-activated protein kinase (MAPK) signaling pathway was activated by JA and CA treatment. Alteration of IL-1 and Hspa1a expression was found by real time reverse transcription polymerase chain reaction, confirming the results of the microarray analysis. Our data demonstrated that polytypic profiles of 167-379 altered genes exist in the mouse hippocampus treated with different compounds known to be therapeutically effective in cerebral ischemia-reperfusion injury, and we were able to identify overlapping genes and pathways among these groups. Therefore, these different compounds may function through both overlapping and distin Topics: Animals; ATP-Binding Cassette Transporters; Capillary Electrochromatography; Cerebral Infarction; Cholic Acid; Drugs, Chinese Herbal; Flavonoids; Gene Expression; Hippocampus; Iridoids; Male; Mice; Microarray Analysis; Mitogen-Activated Protein Kinases; Real-Time Polymerase Chain Reaction; Reperfusion Injury; RNA; Signal Transduction | 2012 |
Synergistic mechanism of gene expression and pathways between jasminoidin and ursodeoxycholic acid in treating focal cerebral ischemia-reperfusion injury.
Jasminoidin and ursodeoxycholic acid are 2 bioactive compounds extracted from Chinese medicine that have been proven to exert a synergistic effect as a combined administration for the treatment of stroke. The aim of this study was to reveal the pharmacogenomic mechanism of this synergistic effect of jasminoidin and ursodeoxycholic acid.. One hundred and fifteen mice with brain damage, induced by focal cerebral ischemia/reperfusion, were divided into 5 groups: jasminoidin-treated, ursodeoxycholic acid-treated, combination-treated, vehicle group, and sham-operated group. Comparative analysis of stroke-related gene expression profiles and Kyoto Encyclopedia of Genes and Genomes pathways among the 3 treatment groups were performed to reveal the mechanism of this synergistic effect.. This study demonstrated that (1) treatment with jasminoidin alone caused similar changes in the pattern of gene expression as those treated with the combination; (2) jasminoidin treatment and the combination treatment had more overlapping changes in gene expression and activated pathways than the ursodeoxycholic acid treatment; (3) Hspa1a and Ppm1e were only up-regulated in the combination-treated group; (4) the nonoverlapping genes Fgf12, Rarα, Map3k4, paxillin (PXN) in the combination-treated group were markedly expressed, and P53 pathway was obviously activated in the combination-treated group.. These findings may suggest that jasminoidin is the major component of the combination, and the combination plays an important role of the synergistic effect in up-regulating expression of gene Hspa1a, genes Fgf12, Rarα, Map3k4 and down-regulating gene PXN, as well as activating P53 pathway. Topics: Animals; Cluster Analysis; Coloring Agents; Databases, Genetic; DNA, Complementary; Drug Synergism; Gene Expression; Gene Expression Profiling; Iridoids; Mice; Microarray Analysis; Principal Component Analysis; Real-Time Polymerase Chain Reaction; Reperfusion Injury; RNA; Signal Transduction; Stroke; Ursodeoxycholic Acid | 2012 |
Cornin ameliorates cerebral infarction in rats by antioxidant action and stabilization of mitochondrial function.
This study was conducted to investigate the efficacy of cornin, an iridoid glycoside, in an experimental cerebral ischemia induced by middle cerebral artery occlusion (MCAO) and reperfusion (I/R), and to elucidate the potential mechanism. Adult male Sprague-Dawley rats were subjected to MCAO for 1 h, then reperfusion for 23 h. Behavioral tests were used to evaluate the damage to central nervous system. The cerebral infarct volume and histopathological damage were assessed to evaluate the brain pathophysiological changes. Spectrophotometric assay methods were used to determine the activities of superoxide dismutase (SOD) and glutathione-peroxidase (GPx). Contents of malondialdehyde (MDA), the generation of reactive oxygen species (ROS) as well as respiratory control ratio and respiratory enzymes of the brain mitochondria were also determined. The results showed that cornin significantly decreased neurological deficit scores, and reduced cerebral infarct volume and degenerative neurons. Meanwhile, cornin significantly increased the brain ATP content, improved mitochondrial energy metabolism, inhibited the elevation of MDA content and ROS generation, and attenuated the decrease of SOD and GPx activities in brain mitochondria. These findings indicate that cornin has protective potential against cerebral ischemia injury and its protective effects may be due to amelioration of cerebral mitochondrial function and its antioxidant property. Topics: Animals; Brain; Calcium; Cell Respiration; Electron Transport; Glutathione Peroxidase; Infarction, Middle Cerebral Artery; Iridoid Glycosides; Iridoids; Male; Malondialdehyde; Membrane Fluidity; Mitochondria; Mitochondrial Membranes; Neuroprotective Agents; Phospholipids; Phytotherapy; Plant Extracts; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Reperfusion Injury; Superoxide Dismutase; Verbena; Water | 2010 |
Cornel iridoid glycoside inhibits inflammation and apoptosis in brains of rats with focal cerebral ischemia.
The capacity of cornel iridoid glycoside (CIG) to suppress the manifestations of ischemic stroke was investigated. CIG was administered to rats by the intragastric route once daily for 7 days. Focal cerebral ischemia was induced by 2 h of middle cerebral artery occlusion followed by 24 h of reperfusion. In non-treated rats large infarct areas were observed within 24 h of reperfusion. Examination of the ischemic cerebral cortex revealed microglia and astrocyte activation, increased interleukin-1beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) concentrations, increased DNA fragmentation in the ischemia penumbra, elevated Bax expression, increased caspase-3 cleavage, and decreased Bcl-2 expression. Pretreatment with CIG decreased the infarct area, DNA fragmentation, IL-1beta and TNF-alpha concentrations, microglia and astrocyte activation, Bax expression, and caspase-3 cleavage while increasing Bcl-2 expression. CIG exerts anti-neuroinflammatory and anti-apoptotic effects which should prove beneficial for prevention or treatment of stroke. Topics: Animals; Apoptosis; Brain Ischemia; Cerebral Infarction; Cornus; Glycosides; Infarction, Middle Cerebral Artery; Inflammation; Interleukin-1beta; Iridoids; Male; Neuroglia; Plant Extracts; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Tumor Necrosis Factor-alpha | 2010 |
Inchinkoto, an herbal medicine, exerts beneficial effects in the rat liver under stress with hepatic ischemia-reperfusion and subsequent hepatectomy.
To investigate the beneficial effects of inchinkoto (ICKT) in the liver after 70% hepatectomy following ischemia reperfusion.. Wistar rats were divided into 3 groups: simple laparotomy and 70% hepatectomy (Hx), 70% hepatectomy following ischemia reperfusion (IR) with vehicle (IRHxV), 70% hepatectomy following IR with ICKT (1 or 2 g/kg of body weight; IRHxK). Vehicle or ICKT was administered for 3 days preoperatively. The hepatoduodenal ligament was clamped for 15 minutes before hepatectomy in the IRHx groups. Rats were killed 1 hours after hepatectomy. In other experiments, the hepatoduodenal ligament was clamped for 30 minutes, with or without ICKT treatment, to evaluate the effect of ICKT on IR injury-induced mortality. Serum transaminase levels and the gene expression of inflammatory cytokines and inducible nitric oxide synthase in the remnant liver were determined. Furthermore, the expression of antioxidant genes was evaluated by PCR array.. The elevation of serum transaminase levels, the upregulation of genes for inflammatory cytokines and inducible nitric oxide synthase, and the increased formation of nitrotyrosine observed in the remnant livers of the IRHxV group were all significantly attenuated by preoperative administration of ICKT in the IRHxK group. The expression of antioxidant genes was also higher in the IRHxK group compared with that of the IRHxV group. Moreover, administration of ICKT significantly reduced the mortality induced by IRHx after 30-minute ischemia.. Preoperative administration of ICKT provides beneficial effects through attenuating inflammatory responses and oxidative stress in the liver following IR and subsequent hepatectomy. Topics: Animals; Antioxidants; Cytokines; Drugs, Chinese Herbal; Glutathione; Hepatectomy; Inflammation Mediators; Iridoid Glycosides; Iridoids; Liver; Male; Nitric Oxide Synthase; Oxidative Stress; p38 Mitogen-Activated Protein Kinases; Polymerase Chain Reaction; Rats; Rats, Wistar; Reactive Nitrogen Species; Reactive Oxygen Species; Reperfusion Injury; Survival Rate; Transaminases; Tyrosine | 2010 |
[Effect of effective components of huanglian jiedu decoction on hypoxia, reoxygenation injury and the expression of VCAM in cultured rat cerebral microvascular endothelial cells].
To investigate the protective mechanism of geniposide, baicalin and berberine on hypoxia and reoxygenation injury in cultured rat cerebral microvascular endothelial cells.. A model of four hours hypoxia and twelve hours reoxygenation injury in rat cerebral microvascular endothelial cells in vitro was established. The injured cells were treated with geniposide (0.128, 0.064, 0.032 mmol x L(-1)), baicalin (0.028, 0.014, 0.007 mmol L(-1)) and berberine (0.024, 0.012, 0.006 mmol L(-1)), respectively. The immunocytochemical method and techniques of image quantitative analysis were used to detect the mean optical density and mean area in order to match the protein expression of VCAM-1. The method of RT-PCR was adopted to observe and match the mRNA expression of VCAM-1.. As compared with the normal group, the mean optical density, the mean area and the mRNA expression of VCAM-1 of model group were significant increased (P < 0.01, P < 0.01, P < 0.01). As compared with the model group, both the mean optical density and the mean area of all treated groups were decreased, and there was significant difference between them (P < 0.01, P < 0.01). As compared with normal group, the mean optical density of baicalin (0.007 mmol x L(-1)) and berberine (0.012, 0.006 mmol x L(-1)) were significant decreased (P < 0.05, P < 0.01, P < 0.01), but there was no significant difference between the other groups and the normal group. As compared with normal group, the mean area of baicalin (0.0014 mmol x L(-1)) was significant decreased (P < 0.05), but there was significant difference between the other groups and the normal group. The mRNA expression of all treated groups was not only lower than that of the model group but also higher than that of the normal group (P < 0.05, P < 0.05).. The results suggest that geniposide, baicalin and berberine, which are effective compositions of huanglian jiedu decoting, can protect hypoxia-reoxygenation injuried rat cerebral microvascular endothelial cells. One of the protected mechanisms is that they can inhibit the expression of VCAM-1. Topics: Animals; Berberine; Cell Hypoxia; Cells, Cultured; Cerebrum; Drugs, Chinese Herbal; Endothelium, Vascular; Flavonoids; Gene Expression; Humans; Hypoxia; Iridoids; Male; Oxygen; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Vascular Cell Adhesion Molecule-1 | 2008 |
[Application of magnetic resonance DW imaging technique in studying treatment of cerebral ischemia in rats by single or combined use of jasminoidin and cholalic acid].
To estimate the therapeutic effect of single or combined use of jasminoidin and cholalic acid on focal cerebral ischemia rat with magnetic resonance-diffusion-weighted imaging (MR-DWI) technique, ultra-microscopy, and neuro-behavior scoring.. The model of cerebral ischemia-reperfusion injury was induced by string method. Three hours after reperfusion, MR-DWI was applied with ultra-microscopy and neuro-behavior test to give evaluation on cerebral ischemic rats, and pathologic, ultramicroscopic observation of tissue were taken as adjuvant measures to comprehensively evaluate the pharmacological effect on ischemia-reperfusion rats and delimit the efficacy of the two different components and their combination.. Compared with the model group, ADC and DCavg values of the foci in all the treated groups had the incrensing trend. There was significant difference arund the foci in the group of combined use of jasminoidin and cholalic acid (P < 0.05).. Combined use of jasminoidin and cholalic acid had protective effects on nerve and brain. MR-DWI technique accompanied with ultramicroscopic observation of tissues and neuro-behavior test is an effective method for evaluating the effect of neuro-protective agent. Topics: Animals; Brain Ischemia; Cholic Acids; Diffusion Magnetic Resonance Imaging; Drug Therapy, Combination; Drugs, Chinese Herbal; Gardenia; Iridoids; Male; Neuroprotective Agents; Phytotherapy; Pyrans; Random Allocation; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Reproducibility of Results; Treatment Outcome | 2006 |
Catalpol modulates the expressions of Bcl-2 and Bax and attenuates apoptosis in gerbils after ischemic injury.
Our previous study described the neuroprotective effects of catalpol in gerbil ischemic model, in which catalpol was shown to prevent hippocampal neurons from death and ameliorate the cognitive ability of the animals. In the study, we focused on investigating the neuroprotective mechanism of catalpol. Animals were randomly assigned three groups as sham-operated, ischemia-treated with saline and ischemia-treated with catalpol. Transient global ischemia was produced by a 5 min occlusion of the bilateral common carotid arteries. Catalpol was intraperitoneally injected at the dose of 5 mg/kg immediately after reperfusion and repeatedly at 12, 24, 48 and 72 h. Histology as well as immunohistochemistry and TUNEL (the terminal deoxynucleotidyl transferase-mediated UTP nick end label) analysis were performed on serial slices through the dorsal hippocampus after gerbils were sacrificed. The results showed that 5 min transient global ischemia followed by 4 days reperfusion caused significant increases in TUNEL-positive and Bax-positive cells in hippocampal CA1 subfield. Catalpol not only significantly reduced TUNEL-positive and Bax-positive cells but also significantly increased Bcl-2-positive cells. All these suggested that catalpol could effectively inhibit apoptosis by modulating the expressions of Bcl-2 and Bax genes. Topics: Animals; Apoptosis; bcl-2-Associated X Protein; Brain Infarction; Brain Ischemia; Disease Models, Animal; Drug Administration Schedule; Drugs, Chinese Herbal; Female; Gene Expression Regulation, Enzymologic; Gerbillinae; Glucosides; Hippocampus; Immunohistochemistry; In Situ Nick-End Labeling; Iridoid Glucosides; Iridoids; Male; Nerve Degeneration; Neuroprotective Agents; Proto-Oncogene Proteins c-bcl-2; Reperfusion Injury; Treatment Outcome | 2006 |
[Pharmacological evaluation of baicalin and jasminoidin and their combination on focal cerebral ischemia-reperfusion injury].
To elucidate the therapeutic effect and the influence on PI3K-Akt-PKB-BAD-CREB-PCREB pathway in focal cerebral ischemia rat responses before and after treatment with baicalin and jasminoidin given alone or in combination.. Rat model of ischemia reperfusion was established with thread. Generally accepted methods were used, including TTC staining, behavior test, as well as micro and ultra microscopy which can dynamically and accurately monitor pathological and physiological changes after cerebral ischemia on earlier period, to evaluate the brain injury induced by ischemia and the attenuations by the drugs. The difference of PI3K-Akt-PKB-BAD-CREB-PCREB expression was detected by western-blot technology.. The combination of baicalin and jasminoidin composition can be potential neuroprotective agent. TTC staining technology combined with behavior grade and ultrmicro-structure observation on brain tissue is effective method to evaluate protective agent, which is related to signal transduction PI3K-Akt-PKB-BAD-CREB-PCREB pathway. The results provide benofical basis for revealing the complex of therapeutic mechanism of traditional Chinese medicine Qingkai Ling (QKL). Topics: Animals; Behavior, Animal; Brain; Brain Ischemia; CREB-Binding Protein; Cyclic AMP Response Element-Binding Protein; Drug Combinations; Flavonoids; Gardenia; Injections; Iridoids; Male; Neuroprotective Agents; Plants, Medicinal; Proto-Oncogene Proteins c-akt; Pyrans; Random Allocation; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Scutellaria; Signal Transduction | 2006 |
A comparative study on the individual and combined effects of baicalin and jasminoidin on focal cerebral ischemia-reperfusion injury.
To compare the individual effects of baicalin and jasminoidin with the combined effect of them on cerebral ischemia-reperfusion injury, and test whether the combined administration of baicalin and jasminoidin can improve the therapeutic effect. Male Sprague-Dawley rats underwent focal cerebral ischemia for 1.5 h and reperfusion for 24 h. Just before reperfusion, tested drugs (baicalin, jasminoidin, a drug combination consisting of baicalin and jasminoidin, or nimodipine) were intravenously treated. Diffusion weighted imaging (DWI) of magnetic resonance imaging (MRI), behavior examination, 2,3,5-triphenyltetrazolium chloride (TTC) staining, histological examination, and real-time PCR for BDNF and caspase-3 were performed. All of the drug treatments could significantly ameliorate the results of TTC and histological examination, and the baicalin/jasminoidin combination did so most prominently. This combination could also significantly ameliorate DWI of MRI and behavior examination results, and promote the expression of BDNF and inhibit the expression of caspase-3. On the whole, both baicalin and jasminoidin have a preventive effect against ischemic stroke, although their effects are not very strong. However, the combination of baicalin and jasminoidin can significantly improve their effectiveness. This may be related to its better regulation on the BDNF and caspase-3. Topics: Analysis of Variance; Animals; Brain; Brain Ischemia; Brain-Derived Neurotrophic Factor; Caspase 3; Disease Models, Animal; Drug Combinations; Drug Therapy, Combination; Drugs, Chinese Herbal; Flavonoids; Iridoids; Male; Neuroprotective Agents; Nimodipine; Pyrans; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Statistics, Nonparametric | 2006 |
Catalpol prevents the loss of CA1 hippocampal neurons and reduces working errors in gerbils after ischemia-reperfusion injury.
Catalpol, an iridoid glycoside, contained richly in the roots of Rehmannia glutinosa, was found for the first time to be of neuroprotection in gerbils subjected to transient global cerebral ischemia. Catalpol (1 mg/kg ip) used immediately after reperfusion and repeatedly at 12, 24, 48 and 72 h significantly rescued neurons in hippocampal CA1 subfield and reduced working errors during behavioral testing. The neuroprotective efficacy of catalpol became more evident when the doses of catalpol were increased to 5 and 10mg/kg. In addition, it was exciting that the significant neuroprotection by catalpol was also evident when catalpol was applied up to 3 h after ischemia. But the neuroprotective efficacy of catalpol became weak when catalpol was given at 6h after ischemia. Of great encouragement was the finding that the neuroprotection of catalpol could be seen not only in a short post-ischemic period (12 days) but also in a long period (35 days). All these indicated that catalpol was truly neuroprotective rather than simply delayed the onset of neuronal damage and might be of therapeutic value for the treatment of global cerebral ischemia. Topics: Analysis of Variance; Animals; Behavioral Symptoms; Dose-Response Relationship, Drug; Gerbillinae; Glucosides; Hippocampus; Iridoid Glucosides; Iridoids; Neurons; Neuroprotective Agents; Reperfusion Injury; Time Factors | 2005 |