Brain MDA Research Articles

The memory-improving effect of Hizikia forsiforme functional oil microcapsule (HFFOM) prepared by subcritical extraction and complex coacervational embedding

Functional foods are prospective in improving memory decline caused by Alzheimer’s disease and aging. The Edible seaweed Hizikia fusiforme functional oil (HFFO) inhibited acetylcholinesterase, prevented cellular neuroinflammation, and improved memory deficits in zebrafish models in the previous studies. To realize its greener preparation and lipid oxidation mitigation and study its effects on higher animals, more investigations are necessary. Herein, sub-critical fluid extraction of HFFO and successive complex coacervation embedding yielded a water-soluble and anti-oxidative microcapsule HFFOM, which displayed in vivo memory-improving effects on LPS-injured zebrafish and normal rodents in different behavior tests. HFFOM can elevate the level of the neurotransmitter acetylcholine while decreasing the levels of MDA, IL-1β, and TNF-α in the zebrafish brain. LC-MS/MS and lipidomic analysis suggested its predominant memory-improving ingredients to be linolenic, erucic, nervonic, arachidonic, linoleic, eicosatrienoic, docosahexaenoic, and docosapentaenoic acids. This study enlightens the potential of HFFOM in developing memory-enhancing functional foods or drugs.

Effects of exogenous ghrelin treatment on oxidative stress, inflammation and histological parameters in a fat-fed streptozotocin rat model

In this study, the anti-inflammatory, antioxidative, and protective effects of ghrelin were investigated in a fat-fed streptozotocin (STZ) rat model and compared with metformin, diabetes and the healthy control groups. Histopathological evaluations were performed on H&E-stained pancreas and brain sections. Biochemical parameters were investigated by enzyme-linked immunosorbent assay. Blood glucose levels were significantly decreased with ghrelin or metformin treatments than the diabetes group. STZ administration increased brain, renal and pancreatic IL-1β, TNF-α and MDA while decreasing GPX, CAT, SOD, and NGF levels. Ghrelin increased renal GPX, CAT, NGF pancreatic GPX, SOD, CAT, NGF and brain SOD, NGF while it decreased renal, pancreatic and brain IL-1β, TNF-α and MDA levels. Ghrelin reduced neuronal loss and degeneration in the cerebral cortex and hippocampus and greatly ameliorated diabetes-related damage in pancreas. In conclusion, the data suggested that ghrelin is an effective candidate as a protectant for reducing the adverse effects of diabetes.

Intranasal Insulin Eases Autism in Rats via GDF-15 and Anti-Inflammatory Pathways.

In rat models, it is well-documented that chronic administration of propionic acid (PPA) leads to autism-like behaviors. Although the intranasal (IN) insulin approach is predominantly recognized for its effects on food restriction, it has also been shown to enhance cognitive memory by influencing various proteins, modulating anti-inflammatory pathways in the brain, and reducing signaling molecules such as interleukins. This study seeks to explore the potential therapeutic benefits of IN insulin in a rat model of autism induced by PPA. Thirty male Wistar albino rats were categorized into three cohorts: the control group, the PPA-induced autism (250 mg/kg/day intraperitoneal PPA dosage for five days) group, treated with saline via IN, and the PPA-induced autism group, treated with 25 U/kg/day (250 µL/kg/day) insulin via IN. All treatments were administered for 15 days. After behavioral testing, all animals were euthanized, and brain tissue and blood samples were collected for histopathological and biochemical assessments. Following insulin administration, a substantial reduction in autism symptoms was observed in all three social behavior tests conducted on the rats. Moreover, insulin exhibited noteworthy capabilities in decreasing brain MDA, IL-2, IL-17, and TNF-α levels within autism models. Additionally, there is a notable elevation in the brain nerve growth factor level (p < 0.05) and GDF-15 (p < 0.05). The assessment of cell counts within the hippocampal region and cerebellum revealed that insulin displayed effects in decreasing glial cells and inducing a significant augmentation in cell types such as the Purkinje and Pyramidal cells. The administration of insulin via IN exhibits alleviating effects on autism-like behavioral, biochemical, and histopathological alterations induced by PPA in rats. Insulin-dependent protective effects show anti-inflammatory, anti-oxidative, and neuroprotective roles of insulin admitted nasally.

Ghrelin ameliorates neuronal damage, oxidative stress, inflammatory parameters, and GFAP expression in traumatic brain injury

ABSTRACT Objective This study investigated the effects of ghrelin on oxidative stress, working memory, inflammatory parameters, and neuron degeneration. Methods TBI was produced with the weight-drop technique. Rats in the G+TBI and TBI+G groups received ghrelin for 7 or 2 days, respectively. The control group received saline. On the 8th day of the study, the brain and blood tissue were taken under anesthesia. Results A significant increase in brain GSH-PX, MDA, IL-1β, TGF-β1, and IL-8 levels and a significant decrease in CAT levels were found in the TBI group compared to the control. Serum MDA, GSH, IL-1β, and IL-8 levels were increased with TBI. Ghrelin treatment after TBI significantly increased the serum GSH, CAT, GSH-PX, and brain GSH and CAT levels, while it significantly decreased the serum MDA, IL-1β, and brain MDA, TGF-β1, and IL-8 levels. Histological evaluations revealed that ghrelin treatment led to a reduction in inflammation, while also significantly ameliorating TBI-induced neuron damage and vascular injuries. Immunohistochemistry staining showed that GFAP staining intensity was significantly increased in the cortex and hippocampus in TBI, and GFAP immunoreactivity was decreased with ghrelin treatment. Conclusion The results from this study suggested that ghrelin may have curative effects on TBI.

Drug Repurposing of Metformin for the Treatment of Haloperidol-Related Behavior Disorders and Oxidative Stress: A Preliminary Study.

A particular attribute of the brain lies in the ability to learn, acquire information from the environment, and utilize the learned information. Previous research has noted that various factors (e.g., age, stress, anxiety, pathological issues), including antipsychotic medications, affect the brain and memory. The current study aimed to reveal the effects of chronic metformin treatment on the cognitive performance of rats and on commonly measured markers for oxidative stress. Wistar male rats (n = 40) were randomly divided into four groups: CTR (n = 10)-control group, METF (n = 10)-animals receiving metformin 500 mg/kg, HAL (n = 10)-animals receiving haloperidol 2 mg/kg, and HALMETF (n = 10)-animals receiving haloperidol 2 mg/kg and metformin 500 mg/kg. The medication was administered daily by oral gavage for 40 days. Memory and learning were assessed using the Morris Water Maze (MWM) test. At the end of the MWM, the rodents were decapitated under anesthesia, and the brain and blood samples were assayed by liquid chromatography for markers of oxidative stress (malondialdehyde, MDA, reduced/oxidized glutathione ratio, GSH/GSSG). The quantification of brain-derived neurotrophic factor (BDNF) was performed using the conventional sandwich ELISA technique. In the HALMETF group, metformin attenuated the negative effects of haloperidol. Brain and plasma MDA levels increased in the HAL group. Brain and plasma GSH/GSSG ratios and BDNF levels did not reveal any differences between groups. In conclusion, metformin treatment limits the deleterious cognitive effects of haloperidol. The effect on oxidative stress markers may also point toward an antioxidant-like effect of metformin, but this needs further tests for confirmation.

Preliminary monosodium glutamate-induced changes in mammary gland receptors and gene expression, water channel, oxidative stress, and some lactogenic biomarkers in lactating rats

BackgroundChanges induced by monosodium glutamate (MSG) can negatively impact milk production and secretion, among other adverse effects. This study aimed to investigate the effects of MSG consumption on receptor gene expression and quantification of hormones and receptors, as well as oxidative stress biomarkers and other lactogenic parameters in lactating animals. Twenty-four female Wistar rats, nine weeks of age, were randomly assigned to four groups, each containing six rats, at parturition. The rats in groups II, III, and IV were given varying doses of monosodium glutamate (MSG); while, group I was given distilled water and served as the control. The experimental period lasted two (2) weeks.ResultsThe groups administered with MSG showed a significant decrease in mammary PRLR gene expression (p < 0.05), as well as a marked reduction (p < 0.05) in mammary PRLR, OXT receptor, AQP-3, brain antioxidant enzymes (SOD, GPx, and CAT), and pituitary SOD compared to the control group (p < 0.05). Furthermore, there was a significant increase (p < 0.05) in reactive oxygen species levels in the serum and mammary gland homogenates, erythrocyte osmotic fragility, and elevated (p < 0.05) brain and pituitary MDA levels in the MSG-administered groups compared to the control group. Daily milk yields were significantly decreased (p < 0.05) in the MSG-administered groups between days 10 and 14 of lactation.ConclusionThe findings of this study suggest that prolonged consumption of MSG could interfere with lactation-associated functions via increased ROS production, reduced antioxidants, decreased AQP-3, mammary prolactin and oxytocin receptors, and prolactin receptor mRNA in lactating Wistar rats.Graphical

Ameliorative Potential of Pumpkin Seed Oil (Cucurbita pepo L.) Against Tramadol-Induced Oxidative Stress.

The increase in the therapeutic use of tramadol in the management of moderate to severe pains in some disease conditions and its unregulated access has led to its associated toxicity and there is little or no information on the protection against its associated toxicity. Considering the medicinal value of pumpkin seed oil, its availability, and neglected use, it becomes necessary to evaluate the possible potential of the seed oil in tramadol-induced oxidative stress in Wister Albino rats. This study used fifty-six (56) albino rats to determine the impact of Cucurbita pepo seed oil (CPSO) on tramadol-induced oxidative stress. The rats were grouped into 7. After a week of acclimatization, rats in group 1 (normal control) had access to water and food, while rats in group 2 received 5mL/Kg (b.w) of normal saline. 100mg/kg of tramadol (TM) was delivered to groups 3-6 to induce toxicity. The third group (TM control) received no treatment, whilst the other 3 groups (TM-CPSO treatment groups) received 5, 2.5, and 1.5mL/Kg of CPSO, respectively. Group 7 received only 5mL/kg CPSO (CPSO group). Similarly, groups 2 through 7 had unrestricted access to food and water for 42days and received treatments via oral intubation once per day. Indicators of oxidative stress were discovered in the brain homogenate. TM toxicity was demonstrated by a considerable increase (P < .05) in the brain MDA level and a significant drop (P < .05) in the brain GSH level, as well as a significant reduction (P < .05) in GPx, catalase, SOD, GST, and quinone reductase activities. The dose-dependent delivery of CPSO was able to restore not only the activity but also the concentrations of the altered markers.

Aloe vera Leaf Extract Reduced BBB Permeability and Improved Neurological Results after Traumatic Brain Injury: The Role of Oxidative Stress.

Recognizing the importance of medicinal plants and the absence of specific medications for traumatic brain injury (TBI) treatment, this study was conducted to evaluate the effects of an aqueous extract of Aloe vera on oxidative stress, blood-brain barrier (BBB) permeability, and neurological scores following TBI. Adult male rats were categorized into five groups: sham, TBI, vehicle, low-dose Aloe vera (LA), and high-dose Aloe vera (HA). We induced diffuse TBI using the Marmaro model and administered the aqueous Aloe vera leaf extract, as well as vehicle, via intraperitoneal injection half an hour after TBI. Neurological outcomes were assessed both before and several hours after TBI. Additionally, oxidative stress factors were measured 24 hr after TBI, and Evans blue content (a BBB permeability index) was determined 5 hr after TBI in both serum and brain. Both LA and HA reduced the increase in BBB permeability after TBI, with HA having a more pronounced effect than LA. Both Aloe vera doses decreased brain MDA levels, increased brain TAC, and lowered both serum and brain PC levels. The impact of Aloe vera on brain oxidative parameters was more significant than on serum. HA also counteracted the declining effects of TBI on neurological outcomes at 4 and 24 hr post-TBI. This study suggests that Aloe vera extract may reduce BBB permeability and improve neurological outcomes after TBI by decreasing oxidative factors and increasing antioxidant factors.

Shexiang Tongxin dropping pills protect against ischemic stroke-induced cerebral microvascular dysfunction via suppressing TXNIP/NLRP3 signaling pathway

Ethnopharmacological relevancePatients with ischemic stroke (IS) often continue to exhibit cerebral microcirculatory dysfunction even after receiving thrombolytic therapy. Enhancing the function of cerebral microvascular endothelia represents a pivotal advancement in the therapeutic strategy for ischemic microcirculatory disturbances. A traditional Chinese medicinal formulation named Shexiang Tongxin Dropping Pills (STDP), has been clinically employed to ameliorate microcirculatory abnormalities. Existing literature attests to the beneficial role of STDP on endothelial cells (ECs). Nevertheless, specific impacts and underlying mechanisms of STDP in rectifying IS-induced cerebral microvascular dysfunction warrant further exploration. Aim of the studyThis investigation seeks to delineate the effects of STDP on cerebral microvascular endothelial damage induced by ischemic stroke and to elucidate the underlying mechanism involved. Materials and methodsMiddle cerebral artery occlusion and reperfusion (MCAO/R) technique was employed to established ischemic stroke model in mice. The therapeutic efficacy of STDP on cerebral microvascular function was assessed through laser speckle contrast imaging, behavioral assays, and histological evaluations. Biochemical markers in the brain tissue, including GSH, SOD, MDA, and ROS, were quantified using specific assay kits. In vitro study, oxygen-glucose deprivation and reperfusion (OGD/R) was performed in bEnd.3 cells. The cytoprotective potential of STDP was then evaluated by measuring cell viability, LDH activity, endothelial permeability, and oxidative stress parameters. Important targets in critical pathway were verified by immunoblotting and immunofluorescence both in mice brain slices and bEnd.3 cells. ResultsSTDP decrease brain infarct size, repaired microvascular cerebral blood flow and attenuated neurological deficiency in MCAO/R mice. Moreover, STDP abolished MCAO/R-induced oxidative stress which was reflected by rescuing GSH content, restoration of SOD activity and T-AOC, reduction of MDA and ROS. Ex vivo, STDP increased cerebral microvascular endothelial cells viability, abolished oxidative stress and decreased their permeability after ODG/R. Mechanistically, STDP significantly suppressed endothelial ROS-TXNIP mediated the activation of NLRP3 inflammasome in vivo and in vitro. ConclusionSTDP improves ischemic stroke-induced cerebral microcirculatory deficits by regulating cerebral microvascular endothelial ROS/TXNIP/NLRP3 signaling pathway.

Effects of chronic diazepam exposure on the behaviors and oxidative stress homeostasis in the eyes and brains of female Japanese medaka

Diazepam (DZP) residue has been frequently detected in wastewater, surface water, and groundwater due to its extensive use over the decades. In this study, we exposed female Japanese medaka (Oryzias latipes) to environmentally relevant doses of DZP (800 and 8000 ng/L) for 4 weeks, aimed to investigate their behavioral responses and possible links with ocular and brain oxidative stress homeostasis. As a result, DZP exposure could significantly reduce swimming activity (800 ng/L) and anxiety (800 and 8000 ng/L), indicating a sedative effect on medaka. The DZP exposure also significantly increased the social interaction in medaka at 8000 ng/L. Furthermore, exposure to DZP could alter the ocular and brain oxidative stress homeostasis in medaka. The ocular CAT activities significantly increased in the 800 ng/L-DZP groups, and the brain SOD, CAT, GST and MDA levels also significantly increased in both DZP exposure groups. Correlation analysis revealed that the ocular and brain oxidative stress induced by DZP exposure might play an important role in their behavioral toxicity to medaka. Our findings highlight the necessity to clarify the exact link between DZP exposure-induced oxidative stress in the neural and sensor systems and its behavioral toxicity to better assess the risks on nontarget aquatic species.

Anti-aging Effect of Rutin in Caenorhabditis elegans and D-Gal-Induced Aging Mouse Model.

Caenorhabditis elegans and D-Gal-induced aging mouse model were used to investigate the anti-aging effect of rutin. The effects of different concentrations of rutin (0, 12.5, 25, and 50 μg/mL) on locomotor behavior, reproductive rate, and lifespan of C. elegans were determined. For establishing the aging mouse model, D-Gal (200 mg/kg) was subcutaneously injected into the back of mice, and mice were treated with rutin (200 mg/kg). At the end of treatment, memory and motor function was assessed by nest building test, open field test, and Y-maze. Serum and brain tissue were collected from each mouse to examine the ROS, lipofuscin, MDA, GSH-Px, and SOD levels. The results showed that rutin prolonged the lifespan of C. elegans, and increased the number of eggs of C. elegans (p < 0.05). In addition, rutin significantly improved the exercise capacity in mice (p < 0.05) and significantly reduced brain tissue ROS (p < 0.05) and MDA (p < 0.01) levels. Meanwhile, rutin could enhance the activity of SOD (p < 0.05) and GSH-Px (p < 0.01) significantly in the serum and brain. In summary, rutin exhibits anti-senescence capabilities which could be ascribed to its antioxidant activities.

Neuroprotective effect of dexpanthenol on rotenone-induced Parkinson's disease model in rats

Parkinson's disease (PD) is the second most common and progressive neurodegenerative disease. This experimental study was designed to investigate the neuroprotective effects of dexpanthenol on antioxidant and anti-inflammatory processes in a rotenone-induced Parkinson's disease model in rats. Twenty-one male rats were randomly divided into 2 groups. The rotenone group (n = 14) was administered rotenone by intrastriatal injection, and the vehicle group (n = 7) was administered DMSO with the same application route. All animals underwent rotational movement testing with apomorphine injection 10 days later. Those with Parkinson's disease model were randomly divided into 2 groups. While 1 ml/kg of saline was applied to the saline group (n = 7), 500 mg/kg was administered to the dexpanthenol group intraperitoneally for 28 days. After 28 days, all rats were euthanized and brain tissue was removed. While striatal areas were evaluated immunohistochemically, brain MDA, TNF-α, and HVA levels were measured to evaluate their anti-oxidative and anti-inflammatory effects. In the dexpanthenol group, the total count (p < 0.001) and intensity (p < 0.001) of dopaminergic neurons in the striatal areas increased compared to the saline group. It was revealed that MDA (nmol/g) (p < 0.001) and TNF-α (pg/g) (p < 0.001) levels decreased in the dexpanthenol group, while HVA (ng/mg) levels increased (p < 0.01). This study suggests that dexpanthenol may have a neuroprotective effect by reducing neuronal loss, oxidative damage, and neuroinflammation in the striatum in rats.

Kinsenoside from Anoectochilus roxburghii (Wall.) Lindl. suppressed oxidative stress to attenuate aging-related learning and memory impairment via ERK/Nrf2 pathway

Ethnopharmacological relevanceAnoectochilusroxburghii (Wall.) Lindl. (AR), as an exceptionally valuable traditional Chinese medicine, has been widely used to treat hepatitis, cancer, diabetes, etc. But, the effects and the primary functioning element of AR on attenuating aging and aging-related learning and memory degradation has not yet been explored. Aim of the studyThis study aimed at exploring the protective property of aqueous extract of AR (AEAR) on alleviation of aging and aging-related learning and memory impairment in vivo, and further investigating the main active ingredient and mechanism of AEAR. Materials and methodsD-galactose (D-gal) induced aging mice and HT22 cells exposed with L-Glutamic acid (Glu) were used as in vivo and in vitro model, separately. The effects of AEAR on aging and aging-related learning and memory degradation were explored by using morris water maze test, immunohistochemistry staining, biochemistry assay, etc. The effects and mechanism of AEAR and Kinsenoside (Kin) on antioxidation in vitro were investigated by cell viability assay, biochemistry assay, qRT-PCR, western blotting and molecular docking studies. ResultsTreatment with AEAR (containing 69.52 ± 0.85% Kin, i.g.) for 63 days, alleviated low growth rate, abnormal brain, liver and thymus index, and decline in learning and memory capability of aging mice. Meanwhile, AEAR inhibited the decreased activities of SOD and GSH-PX, the decline in the ratio of GSH to GSSG, and the increase of MDA in both serum and brain, and also promoted the Nrf2 nuclear translocation in brain of aging mice induced by D-gal. The effects of AEAR on alleviating abnormal physiological characteristics, attenuating learning and memory impairment, and inhibiting oxidative stress in aging mice was similar to or even better than that of Vc. In HT22 cells exposed with Glu, Kin increased the cell viability, up-regulated the activities of SOD and GSH-PX, enhanced the ratio of GSH to GSSG, and down-regulated MDA, which was superior to AEAR. Kin up-regulated the ratio of p-ERK1/2 to ERK1/2, promoted the Nrf2 nuclear translocation and its downstream target genes, i.e. HO-1, NQO-1, GCLC and GCLM expression at the mRNA and protein levels, which were consistent with AEAR. Further, molecular docking results also confirmed that Kin had strong binding energy with ERK1 and ERK2. ConclusionThe present study indicated that Kin could alleviate the oxidative stress in aging mice via activating the ERK/Nrf2 signaling pathway, in order to attenuate aging and aging-related learning and memory impairment, as the main active ingredient of AR.

Resveratrol plays neuroprotective role on ketamine-induced schizophrenia-like behaviors and oxidative damage in mice

This study aimed to determine effects of the resveratrol on ketamine-induced schizophrenia-like behaviors and oxidative damage in mice. Twenty-four male mice were allocated into four experimental groups as control, ketamine (20 mg/kg), resveratrol (80 mg/kg) and co-administration of the ketamine (20 mg/kg) + resveratrol (80 mg/kg). Mice were received resveratrol for 30 days and ketamine was used for an animal model of schizophrenia and was injected from days 16 to 30 of the study. After the drug administration was finished, schizophrenia-like behaviors were evaluated using object recognition test, tail suspension test, forced swimming test and open field test and brain malondialdehyde, glutathione peroxidase, superoxide dismutase and catalase levels were determined. According to the results, ketamine treatment significantly decreased body weight and pretreatment with resveratrol elevated body weight compared to ketamine group (P < 0.05). Ketamine treatment significantly decreased number of the cross in open field test and pretreatment with resveratrol improved i (P < 0.05). Immobility time in tail suspension and forced swimming tests increased in mice treated with ketamine (P < 0.05). Pretreatment with resveratrol diminished immobility time compared to ketamine group (P < 0.05). Ketamine significantly decreased memory deficits while pretreatment with resveratrol significantly reduced the memory deficits induced by ketamine (P < 0.05). Brain MDA increased in both cortical and sub-cortical area in ketamine treated mice while pretreatment with resveratrol decreased ketamine-induced elevation in MDA (P < 0.05). Ketamine significantly decreased brain SOD, GPx and CAT levels while pretreatment with resveratrol improved SOD, GPx and CAT levels (P < 0.05). Findings suggested resveratrol has neuroprotective effects against ketamine-induced behavioral deficits and oxidative damages.

MAC28 Attenuates Neurodegeneration and Restores Cognitive Function via Reducing Peripheral Insulin Resistance, Neuroinflammation, Brain Oxidative Stress, Amyloid‐β Deposition, and Loss of Dendritic Spines in High‐Fat Diet‐induced Obese Rats

AbstractBackgroundLong‐term high‐fat diet (HFD) consumption induces not only peripheral insulin resistance with low‐grade systemic inflammation, but also neuroinflammation and subsequent brain pathologies including neurodegeneration, which can lead to cognitive impairment (1). MAC28, a novel mono‐carbonyl analogue of curcumin, was recently identified as a novel MD‐2 inhibitor, and has been shown to attenuate systemic inflammation (2). However, the effects of MAC 28 on the neuroinflammation, neurodegeneration and cognitive function in the HFD‐induced obese rats have never been studied.MethodMale Wistar rats were fed either a normal diet (ND; n = 8) or HFD (n = 40) for 16 weeks. At week 13, ND‐fed rats were orally administered a vehicle for 4 weeks, while HFD‐fed rats were randomly divided into 5 groups (n = 8/group). Each subgroup was orally administrated either vehicle, 10mg/kg/day of MAC 28, 20mg/kg/day of MAC 28, 40mg/kg/day of MAC 28 or 300 mg/kg/day of metformin for 4 weeks. At the end of experimental protocol, the novel object location (NOL) test was examined in each rat. Brains were rapidly removed to determine brain TLR4‐MD‐2 signaling pathway, inflammatory cytokines, brain oxidative stress, dendritic spine density, amyloid and tau pathology.ResultHFD‐fed rats developed obesity with peripheral insulin resistance. Neuroinflammation was observed in HFD‐fed rats, as evidenced by increased expressions of hippocampal MD‐2, TLR4 and TNF‐α levels. In addition, HFD‐fed rats not only increased the levels of brain MDA, hippocampal amyloid‐β/APP ratio, but also reduced hippocampal dendritic spine density, resulting in cognitive decline. Although all doses of MAC 28 and metformin attenuated peripheral insulin resistance, brain pathologies and cognitive impairment, MAC 28 (20mg/kg/day and 40mg/kg/day) and metformin had the highest efficacy in attenuating peripheral insulin resistance, brain inflammation, brain oxidative stress, amyloid‐β deposition and improving dendritic spines, resulting in restoring cognitive function (P &lt; 0.05, Figure 1).ConclusionThese findings suggest that an obvious neuroprotective effect of MD‐2 inhibitor may be the potential strategy for attenuating neurodegenerative disorders in the obese‐insulin resistant condition.

Utilizing Andrographis paniculata leaves and roots by effective usage of the bioactive andrographolide and its nanodelivery: investigation of antikindling and antioxidant activities through in silico and in vivo studies.

To valorise the bioactive constituents abundant in leaves and other parts of medicinal plants with the objective to minimize the plant-based wastes, this study was undertaken. The main bioactive constituent of Andrographis paniculata, an Asian medicinal plant, is andrographolide (AG, a diterpenoid), which has shown promising results in the treatment of neurodegenerative illnesses. Continuous electrical activity in the brain is a hallmark of the abnormal neurological conditions such as epilepsy (EY). This can lead to neurological sequelae. In this study, we used GSE28674 as a microarray expression profiling dataset to identify DEGs associated with andrographolide and those with fold changes >1 and p-value <0.05 GEO2R. We obtained eight DEG datasets (two up and six down). There was marked enrichment under various Kyoto Encyclopaedia of Genes and Genomes (KEGG) and Gene Ontology (GO) terms for these DEGs (DUSP10, FN1, AR, PRKCE, CA12, RBP4, GABRG2, and GABRA2). Synaptic vesicles and plasma membranes were the predominant sites of DEG expression. AG acts as an antiepileptic agent by upregulating GABA levels. The low bioavailability of AG is a significant limitation of its application. To control these limitations, andrographolide nanoparticles (AGNPs) were prepared and their neuroprotective effect against pentylenetetrazol (PTZ)-induced kindling epilepsy was investigated using network pharmacology (NP) and docking studies to evaluate the antiepileptic multi-target mechanisms of AG. Andrographolide is associated with eight targets in the treatment of epilepsy. Nicotine addiction, GABAergic synapse, and morphine addiction were mainly related to epilepsy, according to KEGG pathway enrichment analysis (p < 0.05). A docking study showed that andrographolide interacted with the key targets. AG regulates epilepsy and exerts its therapeutic effects by stimulating GABA production. Rats received 80 mg/kg body weight of AG and AGNP, phenytoin and PTZ (30 mg/kg i.p. injection on alternate days), brain MDA, SOD, GSH, GABAand histological changes of hippocampus and cortex were observed. PTZ injected rats showed significantly (***p < 0.001) increased kindling behavior, increased MDA, decreased GSH, SOD, GABA activities, compared with normal rats, while treatment AGNPs significantly reduced kindling score and reversed oxidative damage. Finally, we conclude that the leaves and roots of A. Paniculata can be effectively utilized for its major bioactive constituent, andrographolide as a potent anti-epileptic agent. Furthermore, the findings of novel nanotherapeutic approach claim that nano-andrographolide can be successfully in the management of kindling seizures and neurodegenerative disorders.

Beneficial effects of sennoside B on pentylenetetrazole-induced seizures in rats.

Epilepsy is a common disorder affecting approximately 50 million people worldwide. Oxidative stress is known to play an important role in the pathophysiology of diseases, including epilepsy. In this study, we investigated the effects of sennoside B on PTZ-induced seizures in rats. The rats were grouped into Group Electroencephalography and Group Behavioral. Both Groups were divided into eight subgroups, and these subgroups were compared in terms of the time of first myoclonic jerk, Racine's Convulsion Scale, malondialdehyde levels, and brain superoxide dismutase activity. The experimental seizure model was performed with pentylenetetrazol. The spike percentage was significantly lower in groups that received sennoside B, and this beneficial effect was shown to be associated with the dose of sennoside B received. The RCS score was lower and the FJM onset time was higher in the sennoside B-administered groups. Additionally, brain MDA and brain aquaporin-3 levels were lower and brain SOD activity was higher in the sennoside-administered groups. The present study shows the beneficial effects of sennoside B on PTZ-induced convulsion in rats. It is considered that sennoside B which is a natural and safe product would be a good candidate for strengthening the management of epilepsy without serious side effects.

Neurotoxicity of Chlorpyrifos, Carbofuran, and Cypermethrin in Adolescent Rats’ Brain

Chronic exposure to insecticides, even at low levels, has led to chronic neurotoxicity. Adolescent brain is still undergoing important developments, including in the hippocampus. This study investigated neurotoxicity effects of subacute exposure to chlorpyrifos, carbofuran and cypermethrin in the brain of adolescent rats. This study was performed at the Histology, Biochemistry, and Animal House Laboratory of Jember University from November to December 2021. Subjects were divided into five groups: normal, control, chlorpyrifos, carbofuran, and cypermethrin. Short-term memory was evaluated by Y maze test and tissue damage was evaluated by histological examination. Brain MDA levels were determined by thiobarbituric acid reactive substance method to evaluate the oxidative stress effect on the organ. This study showed spontaneous alternation in the Y maze test and the number of pyramidal neurons in hippocampus decreased in the cypermethrin group. There was a significant elevation of brain MDA level in carbofuran and cypermethrin groups. Thus, cypermethrin causes more severe neurotoxicity than carbofuran and chlorpyrifos. Improvements in the insecticide application management are urgently needed to prevent neurotoxicity.

Role of hypoxia inducible factor 1α/Bcl-2/adenovirus E1B 19-kDa interacting protein 3 in alleviating effect of interleukin-4 on cerebral ischemia reperfusion injury in mice.

Cerebral ischemia reperfusion injury (CIRI) is the pathophysiological basis of various cerebrovascular diseases. The aim of this study was to explore the role of HIF-1α/BNIP3 in the alleviating effect of IL-4 on CIRI in mice. Mice were randomly divided into sham operation (Sham), ischemia reperfusion (IR), IL-4, HIF-1α inhibitor 2ME2 and IL-4+2ME2 groups. Middle cerebral artery occlusion model was established. After 24-h reperfusion, neurologic deficit score (NDS) was given. Cerebral infarction volume and brain water content were measured by 2,3,5-triphenyltetrazolium chloride staining and dry-wet weights, respectively. Apoptosis was detected by TUNEL staining. SOD, MDA and ROS levels, and HIF-1α, BNIP3, LC3II and Beclin-1 expressions were detected through colorimetry and Western blotting, respectively. Compared with IR group, NDS, cerebral infarction volume, brain water content, apoptosis rate, and MDA and ROS levels decreased, while SOD, HIF-1α, BNIP3, LC3-II and Beclin-1 levels increased in IL-4 group (P<0.05). 2ME2 and IL-4+2ME2 groups had decreased NDS, cerebral infarction volume, brain water content, apoptosis rate and MDA, ROS, HIF-1α, BNIP3, LC3-II and Beclin-1 levels, but increased SOD level compared with those of IL-4 group (P<0.05). IL-4 reduces apoptosis and oxidative stress through activating the HIF-1α/BNIP3 pathway, thereby alleviating mouse CIRI.

Effects of Rosa roxburghii Tratt glycosides and quercetin on D-galactose-induced aging mice model.

To investigate the effects of RRT (Rosa roxburghii Tratt) glucosides and quercetin on oxidative stress and chronic inflammation in D-galactose-induced aging mice, 90 mice (8 weeks old) were randomly divided into the normal group (NC), aging model group (D-gal), isoquercitrin group (D-gal+isoquercitrin), quercitrin group (D-gal+quercitrin), quercetin group (D-gal+quercetin) and positive control group (D-gal+Metformin). The aging model was established by subcutaneous injection of D-galactose (100 mg/kg). After 42 days of the administration, antioxidant and inflammatory indexes were measured, HE staining was used to investigate pathological changes in liver and brain tissue, and Western blot was used to determine the protein abundance of nuclear factor E2-related factor (Nrf2) and heme oxygenase (HO-1) in the brain. The results showed that, when compared to the NC group, the D-gal group had a significantly lower brain, liver, kidney, and spleen indexes; the contents of MDA, L-1β, IL-6, and TNF-α in serum, liver, and brain were significantly higher, but the levels of CAT, SOD, and GSH-Px were significantly lower. Isoquercitrin, quercitrin, and quercetin significantly increased organ indexes and activities of CAT, SOD, and GSH-Px while decreasing MDA, IL-1β, IL-6, and TNF-α levels in serum, liver, and brain tissues compared to the D-gal group. The morphological changes in the brain and liver tissue were significantly restored by glycosides and quercetin, as observed in HE staining. Furthermore, Western blot results revealed that glycosides and quercetin increased the protein levels of Nrf2, HO-1, and NQO1. Finally, the antioxidant and anti-inflammatory effects of RRT glycoside and quercetin in aging may be attributed to an activated Nrf2/HO-1 signaling pathway. PRACTICAL APPLICATIONS: Aging is characterized by physical changes and dysfunction of numerous biological systems caused by a variety of factors. The oxidative stress and inflammatory effects of RRT glycosides and quercetin on D-galactose-induced aging mice were investigated in this study. RRT glycosides and quercetin were found to protect organ atrophy, liver, and brain tissue in aging mice by regulating oxidative stress and chronic inflammation. It served as the theoretical foundation for the investigation of Rosa roxburghii Tratt as a health product and pharmaceutical raw material.