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

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/3096826 ◽

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.

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JCPyV-Induced MAPK Signaling Activates Transcription Factors during Infection

International Journal of Molecular Sciences ◽

10.3390/ijms20194779 ◽

2019 ◽

Vol 20 (19) ◽

pp. 4779 ◽

Cited By ~ 2

Author(s):

Jeanne K. DuShane ◽

Colleen L. Mayberry ◽

Michael P. Wilczek ◽

Sarah L. Nichols ◽

Melissa S. Maginnis

Keyword(s):

Transcription Factors ◽

Mapk Signaling ◽

Mapk Cascade ◽

Mitogen Activated Protein Kinase ◽

Erk Pathway ◽

Downstream Signaling ◽

Dual Specificity ◽

Extracellular Signal ◽

Mitogen Activated Protein ◽

Underlying Mechanisms

JC polyomavirus (JCPyV), a ubiquitous human pathogen, is the etiological agent of the fatal neurodegenerative disease progressive multifocal leukoencephalopathy (PML). Like most viruses, JCPyV infection requires the activation of host-cell signaling pathways in order to promote viral replication processes. Previous works have established the necessity of the extracellular signal-regulated kinase (ERK), the terminal core kinase of the mitogen-activated protein kinase (MAPK) cascade (MAPK-ERK) for facilitating transcription of the JCPyV genome. However, the underlying mechanisms by which the MAPK-ERK pathway becomes activated and induces viral transcription are poorly understood. Treatment of cells with siRNAs specific for Raf and MAP kinase kinase (MEK) targets proteins in the MAPK-ERK cascade, significantly reducing JCPyV infection. MEK, the dual-specificity kinase responsible for the phosphorylation of ERK, is phosphorylated at times congruent with early events in the virus infectious cycle. Moreover, a MAPK-specific signaling array revealed that transcription factors downstream of the MAPK cascade, including cMyc and SMAD4, are upregulated within infected cells. Confocal microscopy analysis demonstrated that cMyc and SMAD4 shuttle to the nucleus during infection, and nuclear localization is reduced when ERK is inhibited. These findings suggest that JCPyV induction of the MAPK-ERK pathway is mediated by Raf and MEK and leads to the activation of downstream transcription factors during infection. This study further defines the role of the MAPK cascade during JCPyV infection and the downstream signaling consequences, illuminating kinases as potential therapeutic targets for viral infection.

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Cognitive-Enhancing Effect of Quercetin in a Rat Model of Parkinson's Disease Induced by 6-Hydroxydopamine

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2012/823206 ◽

2012 ◽

Vol 2012 ◽

pp. 1-9 ◽

Cited By ~ 45

Author(s):

Napatr Sriraksa ◽

Jintanaporn Wattanathorn ◽

Supaporn Muchimapura ◽

Somsak Tiamkao ◽

Kamoltip Brown ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Spatial Memory ◽

Rat Model ◽

Wistar Rats ◽

Once Daily ◽

Enhancing Effect ◽

Neuron Density ◽

Male Wistar Rats ◽

6 Hydroxydopamine

Oxidative stress has been reported to induce cognitive impairment in Parkinson's disease. This paper aimed to determine the effect of quercetin, a substance possessing antioxidant activity, on the cognitive function in a rat model of Parkinson's disease. Male Wistar rats, weighing 200–250 g, were orally given quercetin at doses of 100, 200, 300 mg/kg BW once daily for a period of 14 days before and 14 days after the unilateral lesion of right substantia nigra induced by 6-hydroxydopamine (6-OHDA). Their spatial memory was assessed at 7 and 14 days of treatment and neuron density was determined, malondialdehyde (MDA) level, the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were evaluated at the end of the experiment. In addition, the activity of acetylcholinesterase (AChE) was also measured. It was found that all doses of quercetin enhanced spatial memory. Therefore, it is suggested that the cognitive-enhancing effect of quercetin occurs partly because of decreased oxidative damage resulting in increased neuron density.

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

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/5305437 ◽

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.

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The Combined Extract of Black Sticky Rice and Dill Improves Poststroke Cognitive Impairment in Metabolic Syndrome Condition

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/9089035 ◽

2019 ◽

Vol 2019 ◽

pp. 1-19 ◽

Cited By ~ 4

Author(s):

Warin Ohnon ◽

Jintanaporn Wattanathorn ◽

Wipawee Thukham-mee ◽

Supaporn Muchimapura ◽

Panakaporn Wannanon ◽

...

Keyword(s):

Oxidative Stress ◽

Metabolic Syndrome ◽

Experimental Period ◽

Underlying Mechanism ◽

Cognitive Enhancer ◽

Anethum Graveolens ◽

Neuroprotective Effects ◽

Neuron Density ◽

Oxidative Stress Status ◽

Male Wistar Rats

Despite the increase in cognitive deficit following stroke in metabolic syndrome (MetS) condition, the therapeutic strategy is still limited. Since oxidative stress and neuroinflammation play the crucial roles on the pathophysiology of aforementioned conditions, the cognitive enhancing effect of the combined extract ofOryza sativaandAnethum graveolenswas considered based on their antioxidant, anti-inflammation, and neuroprotective effects together with the synergistic effect concept. Male Wistar rats weighing 180-220 g were induced metabolic syndrome-like condition by using a high-carbohydrate high-fat diet (HCHF diet). Then, reperfusion injury following cerebral ischemia was induced by the occlusion of right middle cerebral artery and treated with the combined extract ofO. sativaandA. graveolens(OA extract) at doses of 0.5, 5, and 50 mg/kg BW once daily for 21 days. Spatial memory was assessed every 7 days throughout the experimental period. At the end of the study, neuron and glial fibrillary acidic protein- (GFAP-) positive cell densities, the oxidative stress status, AChE, and the expression of proinflammatory cytokines (TNF-α, IL-6) in the hippocampus were determined. The results showed that OA extract at all doses used in this study significantly improved memory together with the reductions of MDA, TNF-α, IL-6, AChE, and density of GFAP-positive cell but increased neuron density in the hippocampus. Taken together, OA is the potential cognitive enhancer in memory impairment following stroke in MetS condition. The possible underlying mechanism may occur partly via the reductions of oxidative stress status, GFAP-positive cell density, and neuroinflammatory cytokines such as TNF-αand IL-6 together with the suppression of AChE activity in the hippocampus. This study suggests that OA is the potential functional ingredient to improve the cognitive enhancer. However, further clinical research is required.

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CONDITION OF HEMODYNAMICS IN THE PULMONARY CIRCULATION OF PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) CONCURRENT WITH METABOLIC SYNDROME WITH HYPERTROPHY AND ATROPHY OF THE MYOCARDIUM

Wiadomości Lekarskie ◽

10.36740/wlek201908114 ◽

2019 ◽

Vol 72 (8) ◽

pp. 1491-1493

Author(s):

Viktor P. Boriak ◽

Svitlana V. Shut’ ◽

Tetiana A. Trybrat ◽

Olena V. Filatova

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Metabolic Syndrome ◽

Right Ventricular ◽

Pulmonary Disease ◽

Pulmonary Circulation ◽

Contractile Function ◽

Ventricular Myocardium ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

The Right

Introduction: In recent years, COPD is observed as not an isolated, but an associated pathology, in particular, concurrent with metabolic syndrome. The aim of the research is to identify the differences in changes of the rheopulmonography parameters (RPG) depending on the presence of hypertrophy or atrophy of the right ventricular myocardium in patients with COPD concurrent with metabolic syndrome.. Materials and methods: We studied changes in rheopulmonography (RPG) in 145 patients with chronic obstructive pulmonary disease (COPD) concurrent with metabolic syndrome. Results: We detected precapillary hypertension of the pulmonary circulation in patients with right ventricular myocardial hypertrophy: anacrotism serration; flattened peak of the systolic wave; decreased Vcp; high placement of incisura; horizontal course of catacrotism; decreased amplitude of the systolic wave (in this case, due to a greater increase in the resistance of the blood flow in the pulmonary vessels than the decreased impact volume of the right ventricle); prolonged Q-a (in this group of patients, it depends more on hypertension of the pulmonary circulation than on the reduction of contractile function of the myocardium). In atrophy of the right ventricular myocardium, the following changes in the RPG were revealed: decreased systolic wave at its dramatic rise; prolonged Q-a (in this case, due to the weakened heart contraction); Vmax reduction (it reflects the reduction of myocardial contractility); in hypertrophy of the myocardium, Vcp., unlike RPG, does not decrease, which is explained by the decrease in the pressure of the pulmonary circulation. Conclusions: We believe that these changes in RPG allow differentiating hypertrophy and right ventricular myocardial atrophy along with established diagnostic criteria, and can be used as markers for the diagnosis and treatment of COPD concurrent with metabolic syndrome.

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Biochemical and Histopathological Evaluation of the Radioprotective Effects of Melatonin Against Gamma Ray-Induced Skin Damage

Current Radiopharmaceuticals ◽

10.2174/1874471012666181120163250 ◽

2019 ◽

Vol 12 (1) ◽

pp. 72-81 ◽

Cited By ~ 11

Author(s):

Dheyauldeen Shabeeb ◽

Masoud Najafi ◽

Ahmed Eleojo Musa ◽

Mansoor Keshavarz ◽

Alireza Shirazi ◽

...

Keyword(s):

Gamma Ray ◽

Histopathological Examination ◽

Radical Scavenging ◽

Limiting Factor ◽

Skin Damage ◽

Exposed Skin ◽

Male Wistar Rats ◽

Time Periods ◽

Skin Damages ◽

The Right

Background:Radiotherapy is one of the treatment methods for cancers using ionizing radiations. About 70% of cancer patients undergo radiotherapy. Radiation effect on the skin is one of the main complications of radiotherapy and dose limiting factor. To ameliorate this complication, we used melatonin as a radioprotective agent due to its antioxidant and anti-inflammatory effects, free radical scavenging, improving overall survival after irradiation as well as minimizing the degree of DNA damage and frequency of chromosomal abrasions.Methods:Sixty male Wistar rats were randomly assigned to 4 groups: control (C), melatonin (M), radiation (R) and melatonin + radiation (MR). A single dose of 30 Gy gamma radiation was exposed to the right hind legs of the rats while 40 mg/ml of melatonin was administered 30 minutes before irradiation and 2 mg/ml once daily in the afternoon for one month till the date of rat’s sacrifice. Five rats from each group were sacrificed 4, 12 and 20 weeks after irradiation. Afterwards, their exposed skin tissues were examined histologically and biochemically.Results:In biochemical analysis, we found that malondialdehyde (MDA) levels significantly increased in R group and decreased significantly in M and MR groups after 4, 12, and 20 weeks, whereas catalase (CAT) and superoxide dismutase (SOD) activities decreased in the R group and increased in M and MR groups during the same time periods compared with the C group (p<0.05). Histopathological examination found there were statistically significant differences between R group compared with the C and M groups for the three different time periods (p<0.005, p<0.004 and p<0.004) respectively, while R group differed significantly with MR group (p<0.013). No significant differences were observed between C and M compared with MR group (p>0.05) at 4 and 20 weeks except for inflammation and hair follicle atrophy, while there were significant effects at 12 weeks (p<0.05).Conclusion:Melatonin can be successfully used for the prevention and treatment of radiation-induced skin injury. We recommend the use of melatonin in optimal and safe doses. These doses should be administered over a long period of time for effective radioprotection and amelioration of skin damages as well as improving the therapeutic ratio of radiotherapy.

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Growth factors in the regulation of reparative response in the presence of peritoneal damage

Pleura and Peritoneum ◽

10.1515/pp-2020-0114 ◽

2020 ◽

Vol 5 (4) ◽

Author(s):

Irina A. Shurygina ◽

Мichael G. Shurygin ◽

Lubov V. Rodionova ◽

Nataliya I. Ayushinova

Keyword(s):

Growth Factors ◽

Growth Factor ◽

Extended Period ◽

Tissue Growth ◽

Tissue Response ◽

Heparin Binding ◽

Lower Quadrant ◽

Male Wistar Rats ◽

The Right ◽

Endothelial Growth Factor

AbstractObjectivesTo study the expression of growth factors in the regulation of tissue repair after peritoneal damage tissue response to peritoneal damage.MethodsExperimental study in 35 male Wistar rats determining the evolution over time of the tissue response to aseptic peritoneal damage. A standardized bowel and peritoneal lesions were created in the right lower quadrant by laparotomy. Then, tissular expression of growth factors was evaluated by multiplex polymerase chain reaction at seven timepoints between 6 h and 30 days, postoperatively.ResultsTissular responses of granulocyte-stimulating factors (Csf2, Csf3), connective tissue growth factor (Ctgf), epidermal growth factors and receptor (Egf, Egfr), fibroblast growth factors (Fgf2, 7 and 10), heparin binding EGF-like growth factor (Hbegf), hepatocyte growth factor (Hgf), insulin-like growth factor-1 (Igf1), mitogenic transforming growth factors (Tgfa, Tgfb1, Tgfbr3), and vascular endothelial growth factor A (Vegfa) were biphasic with a first expression peak at day 3, followed by a more pronounced peak at day 14.ConclusionsWe observed a long-lasting, widespread response of tissular growth factors for at least two weeks after peritoneal damage. To be clinically effective, the prophylaxis of postoperative adhesions might be needed for an extended period of time.

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A NOTE ON THE MATERNAL EFFECT MUTANTS DAUGHTERLESS AND ABNORMAL OOCYTE IN DROSOPHILA MELANOGASTER

Genetics ◽

10.1093/genetics/73.1.73 ◽

1973 ◽

Vol 73 (1) ◽

pp. 73-86

Author(s):

Arthur P Mange ◽

L Sandler

Keyword(s):

Drosophila Melanogaster ◽

Maternal Effect ◽

Sex Chromosome ◽

Chromosome 2 ◽

Dominant Marker ◽

Enhancing Effect ◽

X Irradiation ◽

The Right ◽

Chromosome Breakpoint ◽

Special Region

ABSTRACT Two deficiencies for, and a dominant enhancer of, the second chromosome maternal effect mutant, "daughterless" (da), were induced with X-irradiation. Their properties were studied with respect to both da and the linked maternal effect mutant, "abnormal oocyte" (abo), with the following conclusions. (1) The most probable map positions of da and abo are: J–½–da–2½–abo, where J is a dominant marker located at 41 on the standard map. (2) The da locus is in bands 31CD-F on the polytene chromosome map; abo is to the right of 32A. (3) Because homozygous da individuals survive while individuals carrying da and a deficiency for da are lethal, it is concluded that da is hypomorphic. (4) From a weak da-like maternal effect in heterozygous da females induced by an "Enhancer of da," we have confirmed a previous report that (a) the amount of sex chromosome heterochromatin contributed by the father can influence the severity of the da maternal effect, and (b) the sex chromosome heterochromatin which influences the da effect is different from that which influences the abo effect. (5) The possibility that da and abo are in a special region of chromosome 2 concerned with the regulation of sex chromosome heterochromatin is strengthened by the observation that the Enhancer of da appears to rescue abnormal eggs produced by homozygous abo mothers. (6) The Enhancer of da is a translocation between chromosomes 2 and 3 with the second chromosome breakpoint in the basal heterochromatin; because the enhancing effect maps in this region of chromosome 2, it is possible that autosomal, as well as sex chromosomal, heterochromatin interacts with da and abo.

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Activation of Adenosine A1 Receptor in Ischemic Stroke: Neuroprotection by Tetrahydroxy Stilbene Glycoside as an Agonist

Antioxidants ◽

10.3390/antiox10071112 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1112

Author(s):

Lingyu Ruan ◽

Guanghui Li ◽

Wenlong Zhao ◽

Huihui Meng ◽

Qi Zheng ◽

...

Keyword(s):

Ischemic Stroke ◽

Glutamate Release ◽

Chinese Herb ◽

Adenosine A1 Receptor ◽

Polygonum Multiflorum ◽

Stroke Treatment ◽

Cardiovascular Side Effects ◽

Adenosine A1 ◽

A1 Receptor ◽

Underlying Mechanisms

Ischemic stroke is the main cause of death/disability, posing a great menace to human health. Though efforts to search for therapeutic drugs are ongoing, few of them have succeeded. Adenosine A1 receptor (A1R) activation could ameliorate ischemic injury, representing a very tempting target for stroke treatment. Tetrahydroxy stilbene glycoside (TSG), a potent antioxidant from the well-known Chinese herb Polygonum multiflorum Thunb., has been reported to have notable neuroprotective activities but the underlying mechanisms are elusive. This study investigated the mechanism of TSG focusing on A1R. TSG markedly decreased mortality, neurological deficit score, cerebral infarct size and brain water content of MCAO rats, and ameliorated the disorders in purine metabolism, energy metabolism and antioxidative defense system. TSG helped the survival of SH-SY5Y cells in OGD/R by alleviating oxidative stress and glutamate release, and by maintaining calcium homeostasis. TSG effects were abolished by A1R antagonist DPCPX. Docking and binding assays confirmed the binding of TSG with A1R. In addition, TSG upregulated the A1R level lowered by MCAO and OGD/R. The downstream signals of A1R activation, ERK1/2, HIF-1α and NF-κB contributed to the neuroprotection of TSG. Moreover, void of “well-known” cardiovascular side effects of classical A1R agonists, TSG showcased its great potential for stroke treatment.

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