scholarly journals Phytosome Loading the Combined Extract of Mulberry Fruit and Ginger Protects against Cerebral Ischemia in Metabolic Syndrome Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Nut Palachai ◽  
Jintanaporn Wattanathorn ◽  
Supaporn Muchimapura ◽  
Wipawee Thukham-mee
Keyword(s):  
Oxidative Stress ◽  
Metabolic Syndrome ◽  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Brain Damage ◽  
Neurological Deficit ◽  
Neuroprotective Effect ◽  
Underlying Mechanism ◽  
Neurological Deficit Score ◽  
Mulberry Fruit

The prevalence of ischemic stroke in metabolic syndrome (MetS) is continually increasing and produces a great impact on both qualities of life and annual healthcare budget. Due to the efficiency limitation of the current therapeutic strategy, the poor availability of polyphenol substances induced by the first pass effect and the beneficial effects of mulberry fruit and ginger on brain and MetS-related diseases together with the synergistic concept, the neuroprotective effect against ischemic stroke in MetS condition of phytosome containing the combined extract of mulberry fruit and ginger (PMG) has been considered. To explore the neuroprotective effect and possible underlying mechanism of PMG on brain damage in cerebral ischemic rat with MetS, male Wistar rats were induced MetS by high-carbohydrate high-fat diet (HCHF) for 16 weeks and subjected to the cerebral ischemia/reperfusion injury (CIRI) at the right middle cerebral artery (Rt. MCAO). PMG at doses of 50, 100, and 200 mg/kg were orally fed with for 21 days, and they were assessed brain damage, neurological deficit score, and the changes of oxidative stress markers, inflammatory markers, PPARγ expression, and epigenetic modification via DNMT-1 were performed. All doses of PMG significantly improved brain infarction, brain edema, and neurological deficit score. In addition, the reduction in DNMT-1, MDA level, NF-κB, TNFα, and C-reactive protein together with the increase in SOD, CAT, and GPH-Px activities, and PPARγ expression in the lesion brain were also observed. The current data clearly revealed the neuroprotective effect against cerebral ischemia with MetS condition. The possible underlying mechanism might occur partly via the suppression of DNMT-1 giving rise to the improvement of signal transduction via PPARγ resulting in the decreasing of inflammation and oxidative stress. In conclusion, PMG is the potential neuroprotectant candidate against ischemic stroke in the MetS condition. However, the clinical trial is still essential.

scholarly journals Cerebroprotective Effect against Cerebral Ischemia of the Combined Extract of Oryza sativa and Anethum graveolens in Metabolic Syndrome Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-19 ◽  
Author(s):  
Jintanaporn Wattanathorn ◽  
Warin Ohnon ◽  
Wipawee Thukhammee ◽  
Supaporn Muchmapura ◽  
Panakaporn Wannanon ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Metabolic Syndrome ◽  
Oryza Sativa ◽  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Cortical Area ◽  
Brain Infarction ◽  
Underlying Mechanism ◽  
Anethum Graveolens ◽  
Oxidative Stress Status

The novel strategy against ischemic stroke in metabolic syndrome (MetS) targeting at oxidative stress and inflammation has gained attention due to the limitation of the current therapy. Due to the antioxidant and anti-inflammation of the combined extract of Oryza sativa and Anethum graveolens, the cerebroprotective effect against cerebral ischemia in MetS condition has been focused. Since no data were available, this study was set up to determine the effects of the combined extract of Oryza sativa L. and Anethum graveolens Linn. against ischemic stroke in the animal model of metabolic syndrome. The possible underlying mechanism was also further investigated. Male Wistar rats (180-220 g) were fed with high-carbohydrate high-fat diet (HCHF diet) to induce metabolic syndrome-like condition. Then, MetS rats were subjected to reperfusion injury at the right middle cerebral artery. The combined extract of O. sativa and A. graveolens (OA extract) at doses of 0.5, 5, and 50 mg/kg BW was fed once daily for 21 days. Neurological assessment was performed every 7 days throughout the experimental period. At the end of study, brain infarction volume, neuron and glial fibrillary acidic protein- (GFAP-) positive cell density, the oxidative stress status, the expressions of proinflammatory cytokines (NF-κB, IL-6), and eNOS in the cortical area together with the expression of VCAM-1 and the histological changes of common carotid artery were determined. It was found that OA extract decreased brain infarction, neurological score, oxidative stress status, and inflammatory mediators but increased eNOS expression in the cortical area; the increased VCAM-1 and intima-media thickness together with the reduction of lumen diameter of common carotid artery of MetS eats with MCAO were also mitigated by OA extract. These data suggest the cerebroprotective effect of OA, and the underlying mechanism may occur partly via the improvement of oxidative stress status, inflammation, and brain blood supply.

scholarly journals Scutellarin acts on the AR-NOX Axis to Remediate Oxidative Stress Injury in a Mouse Model of Cerebral Ischemia/Reperfusion Injury

2021 ◽  
Author(s):  
Llin Peng ◽  
Minzhen Deng ◽  
Yan Huang ◽  
Shuang Wu ◽  
Yucheng Cao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Brain Damage ◽  
Ischemia Reperfusion ◽  
Ischemic Injury ◽  
Neurological Function ◽  
Enzyme Linked Immunosorbent Assay ◽  
Stress Injury ◽  
Oxidative Stress Injury

Abstract BackbroundOxidative stress plays an important role in the ischemic stroke induced brain damage. Our previous study showed that Scutellarin protects against ischemic injury in vitro and in vivo induced oxidative damage in rats, and we also reported that the involvement of Aldose reductase (AR) in oxidative stress and cerebral ischemic injury, in this study we furtherly explicit whether the antioxidant effect of Scutellarin on cerebral ischemia injury is related to AR gene regulation and its specific mechanism.MethodsC57BL/6N mice (Wild-type, WT) and AR knockout (AR-/-) mice were subjected to transient middle cerebral artery occlusion (tMCAO) model with 1h occlusion followed by 3d reperfusion, and Scutellarin was administered from 2h before surgery to 3 days after surgery. Subsequently, Neurological function were assessed by the modified Longa score method, the histopathological morphology observed with 2,3,5-triphenyltetrazolium chloride and hematoxylin-eosin staining. Enzyme-linked immunosorbent assay was used to detect the levels of ROS, 4-hydroxynonenal (4-HNE), 8-hydroxydeoxyguanosine (8-OHDG), Neurotrophin-3 (NT-3), poly ADP-ribose polymerase-1 (PARP1) and 3-nitrotyrosine (3-NT) in the ischemic penumbra regions. Quantitative proteomics profiling using quantitative nano-HPLC-MS/MS were performed to compare the protein expression difference between AR-/- and WT mice with or without tMCAO injury. The expression of AR, NOX1, NOX2 and NOX4 in the ipsilateral side of ischemic brain were detected by Real time-PCR, Western blot and immunofluorescence co-staining with NeuN.ResultsScutellarin treatment alleviated brain damage suffered from tMCAO injury such as improved neurological function deficit, brain infarct area and neuronal injury and reduced the expression of oxidation-related products, moreover, also down-regulated tMCAO induced AR mRNA and protein expression.ConclusionsScutellarin would be a potential drug for the treatment of ischemic stroke through regulating AR-NOX Axis modulate oxidative stress injury to play the protective role of cerebral ischemia injury.

Favorable Effects of Astaxanthin on Brain Damage due to Ischemia- Reperfusion Injury

2020 ◽  
Vol 23 (3) ◽  
pp. 214-224 ◽  
Author(s):  
Esra Cakir ◽  
Ufuk Cakir ◽  
Cuneyt Tayman ◽  
Tugba Taskin Turkmenoglu ◽  
Ataman Gonel ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Brain Damage ◽  
Neurological Deficit ◽  
Cell Apoptosis ◽  
Ischemia Reperfusion Injury ◽  
Degradation Products ◽  
Ischemia Reperfusion ◽  
Control Group ◽  
Cortex Cell

Background: Activated inflammation and oxidant stress during cerebral ischemia reperfusion injury (IRI) lead to brain damage. Astaxanthin (ASX) is a type of carotenoid with a strong antioxidant effect. Objective: The aim of this study was to investigate the role of ASX on brain IRI. Methods: A total of 42 adult male Sprague-Dawley rats were divided into 3 groups as control (n=14) group, IRI (n=14) group and IRI + ASX (n=14) group. Cerebral ischemia was instituted by occluding middle cerebral artery for 120 minutes and subsequently, reperfusion was performed for 48 hours. Oxidant parameter levels and protein degradation products were evaluated. Hippocampal and cortex cell apoptosis, neuronal cell count, neurological deficit score were evaluated. Results: In the IRI group, oxidant parameter levels and protein degradation products in the tissue were increased compared to control group. However, these values were significantly decreased in the IRI + ASX group (p<0.05). There was a significant decrease in hippocampal and cortex cell apoptosis and a significant increase in the number of neuronal cells in the IRI + ASX group compared to the IRI group alone (p<0.05). The neurological deficit score which was significantly lower in the IRI group compared to the control group was found to be significantly improved in the IRI + ASX group (p<0.05). Conclusion: Astaxanthin protects the brain from oxidative damage and reduces neuronal deficits due to IRI injury.

scholarly journals Zingiber officinaleMitigates Brain Damage and Improves Memory Impairment in Focal Cerebral Ischemic Rat

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Jintanaporn Wattanathorn ◽  
Jinatta Jittiwat ◽  
Terdthai Tongun ◽  
Supaporn Muchimapura ◽  
Kornkanok Ingkaninan
Keyword(s):  
Cognitive Function ◽  
Cerebral Ischemia ◽  
Brain Damage ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Neuroprotective Effect ◽  
Morris Water Maze Test ◽  
Brain Infarct ◽  
Ginger Rhizome ◽  
The Brain

Cerebral ischemia is known to produce brain damage and related behavioral deficits including memory. Recently, accumulating lines of evidence showed that dietary enrichment with nutritional antioxidants could reduce brain damage and improve cognitive function. In this study, possible protective effect ofZingiber officinale, a medicinal plant reputed for neuroprotective effect against oxidative stress-related brain damage, on brain damage and memory deficit induced by focal cerebral ischemia was elucidated. Male adult Wistar rats were administrated an alcoholic extract of ginger rhizome orally 14 days before and 21 days after the permanent occlusion of right middle cerebral artery (MCAO). Cognitive function assessment was performed at 7, 14, and 21 days after MCAO using the Morris water maze test. The brain infarct volume and density of neurons in hippocampus were also determined. Furthermore, the level of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in cerebral cortex, striatum, and hippocampus was also quantified at the end of experiment. The results showed that cognitive function and neurons density in hippocampus of rats receiving ginger rhizome extract were improved while the brain infarct volume was decreased. The cognitive enhancing effect and neuroprotective effect occurred partly via the antioxidant activity of the extract. In conclusion, our study demonstrated the beneficial effect of ginger rhizome to protect against focal cerebral ischemia.

scholarly journals Encapsulated Mulberry Fruit Extract Alleviates Changes in an Animal Model of Menopause with Metabolic Syndrome

2019 ◽  
Vol 2019 ◽  
pp. 1-23 ◽  
Author(s):  
Jintanaporn Wattanathorn ◽  
Supannika Kawvised ◽  
Wipawee Thukham-mee
Keyword(s):  
Oxidative Stress ◽  
Metabolic Syndrome ◽  
Body Weight ◽  
Weight Gain ◽  
Protein Expression ◽  
Body Weight Gain ◽  
Atherogenic Index ◽  
Fruit Extract ◽  
Mulberry Fruit ◽  
Oxidative Stress Status

Currently, the therapeutic strategy against metabolic syndrome and its complications is required due to the increasing prevalence and its impact. Due to the benefits of both mulberry fruit extract and encapsulation technology, we hypothesized that encapsulated mulberry fruit extract (MME) could improve metabolic parameters and its complication risk in postmenopausal metabolic syndrome. To test this hypothesis, female Wistar rats were induced experimental menopause with metabolic syndrome by bilateral ovariectomy (OVX) and high-carbohydrate high-fat (HCHF) diet. Then, they were orally given MME at doses of 10, 50, and 250 mg/kg BW for 8 weeks and the parameters, such as percentage of body weight gain, total cholesterol, triglycerides, HDL-C, LDL-C, atherogenic index, fasting blood glucose, plasma glucose area under the curve, serum angiotensin-converting enzyme (ACE), oxidative stress status, histology, and protein expression of PPAR-γ, TNF-α, and NF-κB in adipose tissues were determined. MME improved body weight gain, adiposity index, glucose intolerance, lipid profiles, atherogenic index, ACE, oxidative stress status, and protein expression of TNF-αand NF-κB. Moreover, MME attenuated adipocyte hypertrophy and enhanced PPAR-γexpression. Taken altogether, MME decreased metabolic syndrome and its complication via the increased PPAR-γexpression. Therefore, MME is the potential candidate for improving metabolic syndrome and its related complications. However, further research in clinical trial is still necessary.

scholarly journals Memory-Enhancing Effect of a Phytosome Containing the Combined Extract of Mulberry Fruit and Ginger in an Animal Model of Ischemic Stroke with Metabolic Syndrome

2020 ◽  
Vol 2020 ◽  
pp. 1-19
Author(s):  
Jintanaporn Wattanathorn ◽  
Nut Palachai ◽  
Wipawee Thukham-mee ◽  
Supaporn Muchimapura
Keyword(s):  
Metabolic Syndrome ◽  
Ischemic Stroke ◽  
Erk Pathway ◽  
Enhancing Effect ◽  
Neuron Density ◽  
Mulberry Fruit ◽  
Extracellular Signal ◽  
Male Wistar Rats ◽  
Underlying Mechanisms ◽  
The Right

The prevalence of dementia following cerebral ischemia in metabolic syndrome (MetS) condition is increasing, and most of the cases are often severe. Unfortunately, no effective strategy for treating this condition is available. Based on the positive modulation effect of a polyphenol-rich substance on dementia and the improvement in bioavailability and stability of polyphenols induced by the phytosome technique together with the use of the synergistic concept, we hypothesized that a phytosome containing the combined extract of mulberry fruit and ginger (PMG) should mitigate dementia and memory impairment following ischemic stroke in MetS. MetS was induced in male Wistar rats weighing 180-200 g by exposure to a 16-week feeding period of high-carbohydrate high-fat (HCHF) diet. MetS rats were orally given PMG at doses of 50, 100, and 200 mg·kg-1 BW 21 days before and 21 days after the occlusion of the right middle cerebral artery (Rt. MCAO). Then, their spatial memory was determined and the possible underlying mechanisms explored via the alterations of acetylcholinesterase (AChE), neuron density, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), interleukin-6 (IL-6), and signal transduction via extracellular signal-regulated kinase (ERK) pathway in both the cerebral cortex and the hippocampus. It was found that PMG significantly enhanced memory. It also decreased AChE, IL-6, and MDA but increased SOD, CAT, GSH-Px, neuron density, and phosphorylation of ERK. These data suggested the cognitive enhancing effect of PMG. The possible underlying mechanisms might occur partly via the improvement of cholinergic function via the ERK pathway together with the decrease in neurodegeneration induced by the reduction of oxidative stress and inflammation. However, a subchronic toxicity study is also required to assure the safety of PMG consumption before moving forward to a clinical trial study.

Neuroprotective effect of ginkgolide K against acute ischemic stroke on middle cerebral ischemia occlusion in rats

2011 ◽  
Vol 66 (1) ◽  
pp. 25-31 ◽  
Author(s):  
Shuwei Ma ◽  
Huafeng Yin ◽  
Lvyi Chen ◽  
Hongxia Liu ◽  
Ming Zhao ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Acute Ischemic Stroke ◽  
Neuroprotective Effect

scholarly journals Protective Effects of a New C-Jun N-terminal Kinase Inhibitor in the Model of Global Cerebral Ischemia in Rats

Molecules ◽  
2019 ◽  
Vol 24 (9) ◽  
pp. 1722 ◽  
Author(s):  
Mark B. Plotnikov ◽  
Galina A. Chernysheva ◽  
Oleg I. Aliev ◽  
Vera I. Smol’iakova ◽  
Tatiana I. Fomina ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Cerebral Ischemia ◽  
Endothelial Dysfunction ◽  
Neurological Deficit ◽  
Neuroprotective Effect ◽  
Global Cerebral Ischemia ◽  
Hippocampal Ca1 ◽  
Hippocampal Ca1 Area ◽  
Ca1 Area ◽  
The Brain

c-Jun N-terminal kinase (JNK) is activated by various brain insults and is implicated in neuronal injury triggered by reperfusion-induced oxidative stress. Some JNK inhibitors demonstrated neuroprotective potential in various models, including cerebral ischemia/reperfusion injury. The objective of the present work was to study the neuroprotective activity of a new specific JNK inhibitor, IQ-1S (11H-indeno[1,2-b]quinoxalin-11-one oxime sodium salt), in the model of global cerebral ischemia (GCI) in rats compared with citicoline (cytidine-5′-diphosphocholine), a drug approved for the treatment of acute ischemic stroke and to search for pleiotropic mechanisms of neuroprotective effects of IQ-1S. The experiments were performed in a rat model of ischemic stroke with three-vessel occlusion (model of 3VO) affecting the brachiocephalic artery, the left subclavian artery, and the left common carotid artery. After 7-min episode of GCI in rats, 25% of animals died, whereas survived animals had severe neurological deficit at days 1, 3, and 5 after GCI. At day 5 after GCI, we observing massive loss of pyramidal neurons in the hippocampal CA1 area, increase in lipid peroxidation products in the brain tissue, and decrease in local cerebral blood flow (LCBF) in the parietal cortex. Moreover, blood hyperviscosity syndrome and endothelial dysfunction were found after GCI. Administration of IQ-1S (intragastrically at a dose 50 mg/kg daily for 5 days) was associated with neuroprotective effect comparable with the effect of citicoline (intraperitoneal at a dose of 500 mg/kg, daily for 5 days).The neuroprotective effect was accompanied by a decrease in the number of animals with severe neurological deficit, an increase in the number of animals with moderate degree of neurological deficit compared with control GCI group, and an increase in the number of unaltered neurons in the hippocampal CA1 area along with a significant decrease in the number of neurons with irreversible morphological damage. In rats with IQ-1S administration, the LCBF was significantly higher (by 60%) compared with that in the GCI control. Treatment with IQ-1S also decreases blood viscosity and endothelial dysfunction. A concentration-dependent decrease (IC50 = 0.8 ± 0.3 μM) of tone in isolated carotid arterial rings constricted with phenylephrine was observed after IQ-1S application in vitro. We also found that IQ-1S decreased the intensity of the lipid peroxidation in the brain tissue in rats with GCI. 2.2-Diphenyl-1-picrylhydrazyl scavenging for IQ-1S in acetonitrile and acetone exceeded the corresponding values for ionol, a known antioxidant. Overall, these results suggest that the neuroprotective properties of IQ-1S may be mediated by improvement of cerebral microcirculation due to the enhanced vasorelaxation, beneficial effects on blood viscosity, attenuation of the endothelial dysfunction, and antioxidant/antiradical IQ-1S activity.

scholarly journals Uric Acid Protects against Focal Cerebral Ischemia/Reperfusion-Induced Oxidative Stress via Activating Nrf2 and Regulating Neurotrophic Factor Expression

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Bai-liu Ya ◽  
Qian Liu ◽  
Hong-fang Li ◽  
Hong-ju Cheng ◽  
Ting Yu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Uric Acid ◽  
Cerebral Ischemia ◽  
Neurological Deficit ◽  
Focal Cerebral Ischemia ◽  
Ischemia Reperfusion ◽  
Tunel Staining ◽  
Expression Levels ◽  
Cerebral Ischemia Reperfusion ◽  
Nrf2 Signaling Pathway

The aim of this study was to investigate whether uric acid (UA) might exert neuroprotection via activating the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway and regulating neurotrophic factors in the cerebral cortices after transient focal cerebral ischemia/reperfusion (FCI/R) in rats. UA was intravenously injected through the tail vein (16 mg/kg) 30 min after the onset of reperfusion in rats subjected to middle cerebral artery occlusion for 2 h. Neurological deficit score was performed to analyze neurological function at 24 h after reperfusion. Terminal deoxynucleotidyl transferase-mediated dNTP nick end labeling (TUNEL) staining and hematoxylin and eosin (HE) staining were used to detect histological injury of the cerebral cortex. Malondialdehyde (MDA), the carbonyl groups, and 8-hydroxyl-2′-deoxyguanosine (8-OHdG) levels were employed to evaluate oxidative stress. Nrf2 and its downstream antioxidant protein, heme oxygenase- (HO-) 1,were detected by western blot. Nrf2 DNA-binding activity was observed using an ELISA-based measurement. Expressions of BDNF and NGF were analyzed by immunohistochemistry. Our results showed that UA treatment significantly suppressed FCI/R-induced oxidative stress, accompanied by attenuating neuronal damage, which subsequently decreased the infarct volume and neurological deficit. Further, the treatment of UA activated Nrf2 signaling pathway and upregulated BDNF and NGF expression levels. Interestingly, the aforementioned effects of UA were markedly inhibited by administration of brusatol, an inhibitor of Nrf2. Taken together, the antioxidant and neuroprotective effects afforded by UA treatment involved the modulation of Nrf2-mediated oxidative stress and regulation of BDNF and NGF expression levels. Thus, UA treatment could be of interest to prevent FCI/R injury.

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