scholarly journals INVESTIGATION OF THE NEUROPROTECTIVE EFFECT OF LINAGLIPTIN AND CELIPROLOL IN RESERPINE-INDUCED OROFACIAL DYSKINESIA AND ROTENONE-INDUCED NEURODEGENERATION IN RATS

2020 ◽  
pp. 63-71
Author(s):  
VANDANA S. NADE ◽  
VISHAL Y. MARDHEKAR ◽  
UNNATI R. BHOYE ◽  
LAXMAN A. KAWALE
Keyword(s):  
Neuroprotective Effect ◽  
Antioxidant Properties ◽  
Orofacial Dyskinesia ◽  
Behavioral Deficits ◽  
Reserpine Treatment ◽  
Multiple Comparison Test ◽  
Rotenone Treatment ◽  
Ros Accumulation ◽  
Intracellular Ros ◽  
Adrenoceptor Blocker

Objective: Linagliptin, an anti-diabetic agent, proven to play an important role in regulating neuronal plasticity and reduce apoptosis and neuroinflammation by activating downstream AMPK/Sirt 1 pathway, which protects mitochondrial function and suppresses intracellular ROS accumulation and shows antioxidant action. Celiprolol, a β-1selective adrenoceptor blocker used as an anti-hypertensive agent, possesses a direct scavenging activity on oxygen radicals with antioxidant properties. The current study was designed to investigate the combined neuroprotective effect of linagliptin and celiprolol. Methods: Wistar rats of either sex were divided into different groups (n = 6). Eight groups each for Reserpine induced orofacial dyskinesia model and Rotenone induced neurodegeneration model to mimic Parkinson’s like conditions and treated or not with different doses of linagliptin and celiprolol. 24 h after the last dose, animals were subjected to behavioral, biochemical and histopathological evaluations. The data were analyzed by ANOVA and Bonferroni multiple comparison test. Results: Reserpine treatment increased VCMs, tongue protrusion and decreased locomotor activity. Rotenone treatment decreases the motor activity and exploratory ability of the animals. Reserpine as well as rotenone treatments decrease catalase, GSH, SOD and increase the LPO levels as compared to sham group animals. Reserpine and rotenone also showed the presence of ghost cells and vacuolated cytoplasm. Linagliptin and celiprolol alone as well as in combination normalized the behavioral, biochemical and histopathological complications. Conclusion: Linagliptin and Celiprolol showed neuroprotection by antioxidant activity as well as improved reserpine and rotenone-induced behavioral deficits. Both drugs have tenacious potential and can be used clinically with some further investigations.

scholarly journals Neuroprotective Effects against Glutamate-Induced HT-22 Hippocampal Cell Damage and Caenorhabditis elegans Lifespan/Healthspan Enhancing Activity of Auricularia polytricha Mushroom Extracts

2021 ◽  
Vol 14 (10) ◽  
pp. 1001
Author(s):  
Chanin Sillapachaiyaporn ◽  
Panthakarn Rangsinth ◽  
Sunita Nilkhet ◽  
Alison T. Ung ◽  
Siriporn Chuchawankul ◽  
...  
Keyword(s):  
Linoleic Acid ◽  
Caenorhabditis Elegans ◽  
Antioxidant Enzyme ◽  
Neuronal Damage ◽  
Cell Damage ◽  
Neuroprotective Effect ◽  
Antioxidant Properties ◽  
Gas Chromatography Mass Spectrometry ◽  
Auricularia Polytricha ◽  
Ros Accumulation

Oxidative stress is associated with several diseases, particularly neurodegenerative diseases, commonly found in the elderly. The attenuation of oxidative status is one of the alternatives for neuroprotection and anti-aging. Auricularia polytricha (AP), an edible mushroom, contains many therapeutic properties, including antioxidant properties. Herein, we report the effects of AP extracts on antioxidant, neuroprotective, and anti-aging activities. The neuroprotective effect of AP extracts against glutamate-induced HT-22 neuronal damage was determined by evaluating the cytotoxicity, intracellular reactive oxygen species (ROS) accumulation, and expression of antioxidant enzyme genes. Lifespan and healthspan assays were performed to examine the effects of AP extracts from Caenorhabditis elegans. We found that ethanolic extract (APE) attenuated glutamate-induced HT-22 cytotoxicity and increased the expression of antioxidant enzyme genes. Moreover, APE promoted in the longevity and health of the C. elegans. Chemical analysis of the extracts revealed that APE contains the highest quantity of flavonoids and a reasonable percentage of phenols. The lipophilic compounds in APE were identified by gas chromatography/mass spectrometry (GC/MS), revealing that APE mainly contains linoleic acid. Interestingly, linoleic acid suppressed neuronal toxicity and ROS accumulation from glutamate induction. These results indicate that AP could be an exciting natural source that may potentially serves as neuroprotective and anti-aging agents.

scholarly journals Neuroprotective Effect of Ginkgolide B on Bupivacaine-Induced Apoptosis in SH-SY5Y Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Le Li ◽  
Qing-guo Zhang ◽  
Lu-ying Lai ◽  
Xian-jie Wen ◽  
Ting Zheng ◽  
...  
Keyword(s):  
Er Stress ◽  
Caspase 3 ◽  
Neuroprotective Effect ◽  
Antioxidant Property ◽  
Ultrastructural Changes ◽  
Ginkgolide B ◽  
Ros Accumulation ◽  
Intracellular Ros ◽  
Induced Apoptosis ◽  
Mitochondria Complex I

Local anesthetics are used routinely and effectively. However, many are also known to activate neurotoxic pathways. We tested the neuroprotective efficacy of ginkgolide B (GB), an active component of Ginkgo biloba, against ROS-mediated neurotoxicity caused by the local anesthetic bupivacaine. SH-SY5Y cells were treated with different concentrations of bupivacaine alone or following preincubation with GB. Pretreatment with GB increased SH-SY5Y cell viability and attenuated intracellular ROS accumulation, apoptosis, mitochondrial dysfunction, and ER stress. GB suppressed bupivacaine-induced mitochondrial depolarization and mitochondria complex I and III inhibition and increased cleaved caspase-3 and Htra2 expression, which was strongly indicative of activation of mitochondria-dependent apoptosis with concomitantly enhanced expressions of Grp78, caspase-12 mRNA, protein, and ER stress. GB also improved ultrastructural changes indicative of mitochondrial and ER damage induced by bupivacaine. These results implicate bupivacaine-induced ROS-dependent mitochondria, ER dysfunction, and apoptosis, which can be attenuated by GB through its antioxidant property.

scholarly journals The Potential Effects of Phytoestrogens: The Role in Neuroprotection

Molecules ◽  
2021 ◽  
Vol 26 (10) ◽  
pp. 2954
Author(s):  
Justyna Gorzkiewicz ◽  
Grzegorz Bartosz ◽  
Izabela Sadowska-Bartosz
Keyword(s):  
Neuroprotective Effect ◽  
Antioxidant Properties ◽  
Estrogen Therapy ◽  
Neuroprotective Effects ◽  
Potential Health ◽  
Naturally Occurring ◽  
Epigenetic Effects ◽  
Estrogen Synthesis ◽  
Health Promoting ◽  
The Brain

Phytoestrogens are naturally occurring non-steroidal phenolic plant compounds. Their structure is similar to 17-β-estradiol, the main female sex hormone. This review offers a concise summary of the current literature on several potential health benefits of phytoestrogens, mainly their neuroprotective effect. Phytoestrogens lower the risk of menopausal symptoms and osteoporosis, as well as cardiovascular disease. They also reduce the risk of brain disease. The effects of phytoestrogens and their derivatives on cancer are mainly due to the inhibition of estrogen synthesis and metabolism, leading to antiangiogenic, antimetastatic, and epigenetic effects. The brain controls the secretion of estrogen (hypothalamus-pituitary-gonads axis). However, it has not been unequivocally established whether estrogen therapy has a neuroprotective effect on brain function. The neuroprotective effects of phytoestrogens seem to be related to both their antioxidant properties and interaction with the estrogen receptor. The possible effects of phytoestrogens on the thyroid cause some concern; nevertheless, generally, no serious side effects have been reported, and these compounds can be recommended as health-promoting food components or supplements.

scholarly journals Molecular and Biochemical Pathways of Catalpol in Alleviating Diabetes Mellitus and Its Complications

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 323
Author(s):  
Subrat Kumar Bhattamisra ◽  
Hui Min Koh ◽  
Shin Yean Lim ◽  
Hira Choudhury ◽  
Manisha Pandey
Keyword(s):  
Diabetes Mellitus ◽  
Diabetic Complications ◽  
Inflammatory Markers ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Neuroprotective Effect ◽  
Antioxidant Properties ◽  
Beneficial Effects ◽  
Ppar Γ ◽  
High Glucose Condition ◽  
Anti Inflammatory

Catalpol isolated from Rehmannia glutinosa is a potent antioxidant and investigated against many disorders. This review appraises the key molecular pathways of catalpol against diabetes mellitus and its complications. Multiple search engines including Google Scholar, PubMed, and Science Direct were used to retrieve publications containing the keywords “Catalpol”, “Type 1 diabetes mellitus”, “Type 2 diabetes mellitus”, and “diabetic complications”. Catalpol promotes IRS-1/PI3K/AKT/GLUT2 activity and suppresses Phosphoenolpyruvate carboxykinase (PEPCK) and Glucose 6-phosphatase (G6Pase) expression in the liver. Catalpol induces myogenesis by increasing MyoD/MyoG/MHC expression and improves mitochondria function through the AMPK/PGC-1α/PPAR-γ and TFAM signaling in skeletal muscles. Catalpol downregulates the pro-inflammatory markers and upregulates the anti-inflammatory markers in adipose tissues. Catalpol exerts antioxidant properties through increasing superoxide dismutase (sod), catalase (cat), and glutathione peroxidase (gsh-px) activity in the pancreas and liver. Catalpol has been shown to have anti-oxidative, anti-inflammatory, anti-apoptosis, and anti-fibrosis properties that in turn bring beneficial effects in diabetic complications. Its nephroprotective effect is related to the modulation of the AGE/RAGE/NF-κB and TGF-β/smad2/3 pathways. Catalpol produces a neuroprotective effect by increasing the expression of protein Kinase-C (PKC) and Cav-1. Furthermore, catalpol exhibits a cardioprotective effect through the apelin/APJ and ROS/NF-κB/Neat1 pathway. Catalpol stimulates proliferation and differentiation of osteoblast cells in high glucose condition. Lastly, catalpol shows its potential in preventing neurodegeneration in the retina with NF-κB downregulation. Overall, catalpol exhibits numerous beneficial effects on diabetes mellitus and diabetic complications.

Acute Stress Induced Behavioral Deficits In Rats: Relationship With Oxidative Stress, Leptin And HPA Axis

2019 ◽  
Vol 41 (5) ◽  
pp. 859-859
Author(s):  
Erum Shireen Erum Shireen ◽  
Wafa Binte Ali Wafa Binte Ali ◽  
Maria Masroor Maria Masroor ◽  
Saeeda Bano Saeeda Bano ◽  
Samina Iqbal Samina Iqbal ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Open Field ◽  
Hpa Axis ◽  
Acute Stress ◽  
Antioxidant Properties ◽  
Oxidative Enzymes ◽  
Behavioral Deficits ◽  
Glucose Estimation ◽  
Dark Transition

Acute exposure to stress is connected to many disorders that promote the toxicity of oxygen radical generators leading to increase in the levels of enzymes and also the activation of the HPA axis. The present study uses a preclinical approach to elucidate some prospective stress-induced behavioral and biochemical effects. The aim of current study was to investigate the relationship between stress and behavioral changes after exposing animals to 2h immobilization stress. We also evaluated the concentration of corticosterone, glucose and endogenous leptin levels in unstressed and stressed animals to explore the possible role of HPA axis in the modulation of stressed induced behavioral deficits. Rats were divided into stressed and unstressed groups. Behavioral activities were monitored in open field activity and light dark transition box after the termination of 2h immobilization period. Animals were then decapitated and plasma samples were collected for catalase, SOD, corticosterone, and glucose estimation. Results showed that exposure to acute stress produced a significant decrease in the activity of rats in the novel environment (open field) and light dark transition box. On the other hand, concomitant elevated level of peripheral markers of oxidative stress such as oxidative enzymes, corticosterone and endogenous leptin were also observed. Therefore, current study seems to suggest an important role of compounds having antioxidant properties for the treatment of stress and related disorders.

scholarly journals Bi-phasic effect of gelatin in myogenesis and skeletal muscle regeneration

2021 ◽  
Author(s):  
Xiaoling Liu ◽  
Er Zu ◽  
Xinyu Chang ◽  
Xiaowei Ma ◽  
Ziqi Wang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Antioxidant System ◽  
Muscle Regeneration ◽  
Chain Complex ◽  
Skeletal Muscle Regeneration ◽  
High Dose ◽  
Mild Stress ◽  
Ecm Remodeling ◽  
Ros Accumulation ◽  
Intracellular Ros

Skeletal muscle regeneration requires extracellular matrix (ECM) remodeling, including an acute and transient breakdown of collagen that produces gelatin. Although the physiological function of this process is unclear, it has inspired us to apply gelatin to injured skeletal muscle for a potential pro-regenerative effect. Here we elaborate on a bi-phasic effect of gelatin in skeletal muscle regeneration, mediated by hormetic effects of reactive oxygen species (ROS). Low-dose gelatin stimulates ROS production from NADPH oxidase 2 (NOX2) and simultaneously upregulates antioxidant system for cellular defense, reminiscent of the adaptive compensatory process during mild stress. This response triggers the release of myokine IL-6 that stimulates myogenesis and facilitates muscle regeneration. By contrast, high-dose gelatin stimulates ROS overproduction from NOX2 and mitochondrial chain complex, and ROS accumulation by suppressing antioxidant system, triggering release of TNFα, which inhibits myogenesis and regeneration. Our results have revealed a bi-phasic role of gelatin in regulating skeletal muscle repair mediated by intracellular ROS, antioxidant system, and cytokines (IL-6 and TNFα) signaling.

scholarly journals NEUROPROTECTIVE EFFECT OF ARTOCARPUS LAKOOCHA EXTRACT AND OXYRESVERATROL AGAINST HYDROGEN PEROXIDE-INDUCED TOXICITY IN SH-SY5Y CELLS

2017 ◽  
Vol 9 (10) ◽  
pp. 229 ◽  
Author(s):  
Hasriadi . ◽  
Matusorn Wong-on ◽  
Phakhamon Lapphanichayakool ◽  
Nanteetip Limpeanchob
Keyword(s):  
Hydrogen Peroxide ◽  
Lipid Peroxidation ◽  
Cell Viability ◽  
Mitochondrial Function ◽  
Neuroprotective Effect ◽  
Neuroblastoma Cells ◽  
Effective Protection ◽  
Intracellular Ros ◽  
Medical Plant ◽  
Continuous Presence

Objective: Artocarpus lakoocha Roxb. is a traditional medical plant native to Southeast Asia and used as a dried aqueous extract so-called puag haad. Its role (and its major ingredient, oxyresveratrol) as an antioxidant neuroprotectant were explored.Methods: Differentiated SH-SY5Y neuroblastoma cells in 96-well plates were challenged with 200 µM H2O2 for 4 h and either Trolox (100 µM), oxyresveratrol (5-100 µM), or puag haad (1.2-25 µg/ml) applied 2 h before H2O2 or for 20 h after H2O2 washout. Cell viability, mitochondrial function, intracellular ROS, and lipid peroxidation were assessed.Results: Continuous presence of both H2O2 and antioxidant reduced mitochondrial function by ~50% but only by 30% with antioxidant. Sustained 24 h H2O2 showed no recoveries with antioxidants. Cell viability was modestly restored when antioxidants accompanied H2O2 for 4 h and both washed for another 20 h, but little recovery of mitochondrial function even though antioxidants removed ROS and prevent lipid peroxidation. Antioxidants added for 20 h after H2O2 marginally improve mitochondria and modestly restore cell viability, but lipid peroxidation was completely reversed.Conclusion: These results show that mitochondrial protection was illusive, yet both tested compounds, puag haad and oxyresveratrol, improved cell viability and especially ROS levels and lipid peroxidation. The potency oxyresveratrol on the redox-sensitive expression of antioxidant enzymes and its pharmacokinetics suggests that oral puag haad could provide effective protection in transient neurodegenerative disease. 

scholarly journals Human Lactoferrin Induces Apoptosis-Like Cell Death in Candida albicans: Critical Role of K+-Channel-Mediated K+ Efflux

2008 ◽  
Vol 52 (11) ◽  
pp. 4081-4088 ◽  
Author(s):  
María T. Andrés ◽  
Monica Viejo-Díaz ◽  
José F. Fierro
Keyword(s):  
Candida Albicans ◽  
Chromatin Condensation ◽  
Critical Role ◽  
Blocking Agent ◽  
Human Lactoferrin ◽  
K Channel ◽  
Mitochondrial Activity ◽  
Channel Blockers ◽  
Ros Accumulation ◽  
Intracellular Ros

ABSTRACT Human lactoferrin (hLf) induced an apoptosis-like phenotype in Candida albicans cells, which includes phosphatidylserine externalization, nuclear chromatin condensation, DNA degradation, and increased reactive oxygen species (ROS) production. Intracellular ROS accumulation was seen to correlate with candidacidal activity in hLf-treated cells. Mitochondrial activity was involved as indicated by mitochondrial depolarization and increased hLf resistance of cells preincubated with sordarin or erythromycin, the latter of which inhibits protein synthesis in mitoribosomes. Interestingly, Cl−- and K+-channel blockers prevented the hLf antimicrobial activity, but only when cells were pretreated with the blocking agent (tetraethylammonium) prior to the hLf-induced K+-release period. These results indicate for the first time that K+-channel-mediated K+ efflux is required for the progression of apoptosis-like process in yeast, suggesting that this essential apoptotic event of higher eukaryotes has been evolutionary conserved among species ranging from yeasts to humans.

scholarly journals Ionizing Radiation Upregulates Glutamine Metabolism and Induces Cell Death via Accumulation of Reactive Oxygen Species

2021 ◽  
Vol 2021 ◽  
pp. 1-22
Author(s):  
Pengfei Yang ◽  
Xiangxia Luo ◽  
Jin Li ◽  
Tianyi Zhang ◽  
Xiaoling Gao ◽  
...  
Keyword(s):  
Cell Death ◽  
Ionizing Radiation ◽  
Tumor Cells ◽  
Metabolic Flux ◽  
Glutamine Metabolism ◽  
X Rays ◽  
Ros Accumulation ◽  
Intracellular Ros ◽  
Radiation Induced ◽  
Excessive Accumulation

Glutamine metabolism provides energy to tumor cells and also produces reactive oxygen species (ROS). Excessive accumulation of ROS can damage mitochondria and eventually lead to cell death. xCT (SLC7A11) is responsible for the synthesis of glutathione in order to neutralize ROS. In addition, mitophagy can remove damaged mitochondria to keep the cell alive. Ionizing radiation kills tumor cells by causing the accumulation of ROS, which subsequently induces nuclear DNA damage. With this in mind, we explored the mechanism of intracellular ROS accumulation induced by ionizing radiation and hypothesized new methods to enhance the effect of radiotherapy. We used MCF-7 breast cancer cells and HCT116 colorectal cancer cells in our study. The above-mentioned cells were irradiated with different doses of X-rays or carbon ions. Clone formation assays were used to detect cell proliferation, enzyme-linked immunosorbent assay (ELISA) detected ATP, and glutathione (GSH) production, while the expression of proteins was detected by Western blot and quantitative real-time PCR analysis. The production of ROS was detected by flow cytometry, and immunofluorescence was used to track mitophagy-related processes. Finally, BALB/C tumor-bearing nude mice were irradiated with X-rays in order to further explore the protein expression found in tumors with the use of immunohistochemistry. Ionizing radiation increased the protein expressions of ASCT2, GLS, and GLUD in order to upregulate the glutamine metabolic flux in tumor cells. This caused an increase in ATP secretion. Meanwhile, ionizing radiation inhibited the expression of the xCT (SLC7A11) protein and reduced the generation of glutathione, leading to excessive accumulation of intracellular ROS. The mitophagy inhibitor, or knockdown Parkin gene, is able to enhance the ionizing radiation-induced ROS production and increase nucleus DNA damage. This combined treatment can significantly improve the killing effect of radiation on tumor cells. We concluded that ionizing radiation could upregulate the glutamine metabolic flux and enhance ROS accumulation in mitochondria. Ionizing radiation also decreased the SLC7A11 expression, resulting in reduced GSH generation. Therefore, inhibition of mitophagy can increase ionizing radiation-induced cell death.

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