Icariin prevents methylmercury-induced experimental neurotoxicity: Evidence from cerebrospinal fluid, blood plasma, brain samples, and in-silico investigations

Heliyon, Journal Year: 2024, Volume and Issue: 10(1), P. e24050 - e24050

Published: Jan. 1, 2024

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease that causes significant neurodegeneration. Methylmercury (MeHg) neurotoxin induces axonal neurodegeneration and motor nerve degeneration by destroying oligodendrocytes, degenerating white matter, inducing apoptosis, excitotoxicity, reducing myelin basic protein (MBP). This study examines the inhibition of SIRT-1 (silence information regulator 1), Nrf-2 (nuclear factor E2-related 2), HO-1 (heme oxygenase TDP-43 (TAR-DNA-binding 43) accumulation in context ALS, as well modulation these proteins icariin (15 30 mg/kg, orally), glycoside flavonoid with neuroprotective properties. Neuroprotective activates SIRT-1, Nrf-2, HO-1, mitigating inflammation neuronal injury disorders. In-vivo in-silico testing experimental ALS models confirmed efficacy modulating cellular targets. The addition sirtinol 10 an inhibitor helps determine effectiveness icariin. In this study, we also examined neurobehavioral, neurochemical, histopathological, LFB (Luxol fast blue) markers various biological samples, including Cerebrospinal fluid (CSF), blood plasma, brain homogenates (Cerebral Cortex, Hippocampus, Striatum, mid-brain, Cerebellum). These results demonstrate administration ameliorates mechanism underlying benefits likely related to regulating signaling pathways.

Language: Английский

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PI3K/AKT/mTOR signalling inhibitor chrysophanol ameliorates neurobehavioural and neurochemical defects in propionic acid-induced experimental model of autism in adult rats

Metabolic Brain Disease, Journal Year: 2022, Volume and Issue: 37(6), P. 1909 - 1929

Published: June 10, 2022

Language: Английский

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Nrf2/HO-1 Signaling Stimulation through Acetyl-11-Keto-Beta-Boswellic Acid (AKBA) Provides Neuroprotection in Ethidium Bromide-Induced Experimental Model of Multiple Sclerosis

Genes, Journal Year: 2022, Volume and Issue: 13(8), P. 1324 - 1324

Published: July 25, 2022

Multiple sclerosis (MS) is a severe immune-mediated neurological disease characterized by neuroinflammation, demyelination, and axonal degeneration in the central nervous system (CNS). This frequently linked to motor abnormalities cognitive impairments. The pathophysiological hallmarks of MS include inflammatory injury, white matter degeneration, development CNS lesions that result neuronal degeneration. Several studies suggested downregulation nuclear factor erythroid-2-related factor-2 (Nrf2)/Heme oxygenase-1 (HO-1) signaling causative for pathogenesis. Acetyl-11-keto-β-boswellic acid (AKBA) an active pentacyclictriterpenoid obtained from Boswellia serrata, possessing antioxidant anti-inflammatory properties. present study explores protective potential AKBA on behavioral, molecular, neurochemical, gross pathological abnormalitiesandhistopathological alterations H&E LFB staining techniques experimental model multiple sclerosis, emphasizing increase inNrf2/HO-1 levels brain. Moreover, we also examine effect intensity myelin basic protein (MBP) CSF rat brain homogenate. Specific apoptotic markers (Bcl-2, Bax, andcaspase-3) were estimated Neuro behavioralabnormalities rats examined using actophotometer, rotarod test, beam crossing task (BCT),and Morris water maze (MWM). 50 mg/kg 100 given orally day 8 35 alleviate symptoms EB-injected rats. Furthermore, cellular, neurotransmitter, neuroinflammatory cytokine, oxidative stress whole homogenate, blood plasma, cerebral spinal fluid investigated. shows upregulates level proteins such as Nrf2 HO-1 restores altered neurochemical levels, potentially preventing during progression.

Language: Английский

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Guggulsterone Selectively Modulates STAT-3, mTOR, and PPAR-Gamma Signaling in a Methylmercury-Exposed Experimental Neurotoxicity: Evidence from CSF, Blood Plasma, and Brain Samples

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 61(8), P. 5161 - 5193

Published: Jan. 3, 2024

Language: Английский

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Activation of IGF-1/GLP-1 Signalling via 4-Hydroxyisoleucine Prevents Motor Neuron Impairments in Experimental ALS-Rats Exposed to Methylmercury-Induced Neurotoxicity

Molecules, Journal Year: 2022, Volume and Issue: 27(12), P. 3878 - 3878

Published: June 16, 2022

Amyotrophic lateral sclerosis (ALS) is a severe adult motor neuron disease that causes progressive neuromuscular atrophy, muscle wasting, weakness, and depressive-like symptoms. Our previous research suggests mercury levels are directly associated with ALS progression. MeHg+-induced characterised by oligodendrocyte destruction, myelin basic protein (MBP) depletion, white matter degeneration, leading to demyelination death. The selection of MeHg+ as potential neurotoxicant based on our evidence it has been connected the development ALS-like characteristics. It glutamate-mediated excitotoxicity, calcium-dependent neurotoxicity, an phenotype. Dysregulation IGF-1/GLP-1 signalling bioactive amino acid 4-hydroxyisoleucine (HI) from Trigonella foenum graecum acts insulin mimic in rodents increases sensitivity. This study examined neuroprotective effects 4-HI MeHg+-treated Wistar rats symptoms, emphasising brain IGF1/GLP-1 activation. Furthermore, we investigated effect MBP rat homogenate, cerebrospinal fluid (CSF), blood plasma, cell death indicators such caspase-3, Bax, Bcl-2. Rats were assessed for muscular strength, locomotor deficits, depressed behaviour, spatial learning Morris water maze (MWM) measure neurobehavioral abnormalities. Doses given orally 42 days model at 50 mg/kg or 100 ameliorate neurological dysfunctions. Additionally, neurotransmitters oxidative stress markers homogenates. findings suggest benefits reducing behavioural, neurochemical, histopathological abnormalities exposed methylmercury.

Language: Английский

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Activating SIRT-1 Signalling with the Mitochondrial-CoQ10 Activator Solanesol Improves Neurobehavioral and Neurochemical Defects in Ouabain-Induced Experimental Model of Bipolar Disorder

Pharmaceuticals, Journal Year: 2022, Volume and Issue: 15(8), P. 959 - 959

Published: Aug. 2, 2022

Bipolar disorder (BD) is a chronic mental illness characterized by mood fluctuations that range from depressive lows to manic highs. Several studies have linked the downregulation of SIRT-1 (silent mating type information regulation-2 homologs) signaling onset BD and other neurological dysfunctions. This research aimed look into neuroprotective potential Solanesol (SNL) in rats given ICV-Ouabain injections, focusing on its effect activation brain. Ouabain, found hypothalamic medullary neurons, an endogenous inhibitor brain Na+/K+ ATPase. The inhibition ATPase Ouabain may also result changes neurotransmission within central nervous system. SNL Solanaceae family active phytoconstituent produced plant Nicotiana tabacum. used as precursor for production CoQ10 (Coenzyme Q10), powerful antioxidant compound. In current study, lithium (Li), important stabilizer drug, was control. study looked at dosages 40 80 mg/kg ICV-OUA injections caused BD-like neurobehavioral neurochemical defects Wistar rats. were placed eight groups (n = 6) administered 1 mM/0.5 µL three days. Neurochemical assessments done rat homogenates, CSF, blood plasma samples end experiment protocol schedule. Long-term administration been shown decrease number rearing crossings reduce time spent center, locomotor activities, immobility time. Solansesol treatment gradually raises amount ATPase, limiting severity behavioural symptoms. These findings revealed increases levels plasma, homogenate samples. Moreover, homogenates samples, modulates apoptotic markers such Caspase-3, Bax (pro-apoptotic), Bcl-2 (anti-apoptotic). Mitochondrial-ETC complex enzymes, including complex-I, II, IV, V, CoQ10, restored following long-term treatment. Furthermore, lowered inflammatory cytokines (TNF-α, IL-1β) while restoring neurotransmitter (serotonin, dopamine, glutamate, acetylcholine) decreasing oxidative stress markers. Histological examinations validated Solanesol's protective effect. As result, our suggest SNL, signalling activator, be promising therapeutic approach

Language: Английский

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Acetyl-11-keto-beta boswellic acid(AKBA) modulates CSTC-pathway by activating SIRT-1/Nrf2-HO-1 signalling in experimental rat model of obsessive-compulsive disorder: Evidenced by CSF, blood plasma and histopathological alterations

NeuroToxicology, Journal Year: 2023, Volume and Issue: 98, P. 61 - 85

Published: Aug. 5, 2023

Language: Английский

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Matrine mediated neuroprotective potential in experimental multiple sclerosis: Evidence from CSF, blood markers, brain samples and in-silico investigations

Journal of Neuroimmunology, Journal Year: 2023, Volume and Issue: 384, P. 578200 - 578200

Published: Sept. 16, 2023

Language: Английский

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Beta-Boswellic Acid Reverses 3-Nitropropionic Acid-Induced Molecular, Mitochondrial, and Histopathological Defects in Experimental Rat Model of Huntington’s Disease

Biomedicines, Journal Year: 2022, Volume and Issue: 10(11), P. 2866 - 2866

Published: Nov. 9, 2022

Huntington's disease (HD) is distinguished by a triple repeat of CAG in exon 1, an increase poly Q the Htt gene, and loss GABAergic medium spiny neurons (MSN) striatum white matter cortex. Mitochondrial ETC-complex dysfunctions are involved pathogenesis HD, including neuronal energy loss, synaptic neurotrophic decline, inflammation, apoptosis, grey destruction. A previous study has demonstrated that beta Boswellic acid (β-BA), naturally occurring phytochemical, several neuroprotective properties can reduce pathogenic factors associated with various neurological disorders. The current investigation aimed to investigate potential β-BA at oral doses 5, 10, 15 mg/kg alone, as well conjunction potent antioxidant vitamin E (8 mg/kg, orally) 3-NP-induced experimental HD rats. Adult Wistar rats were separated into seven groups, 3-NP, dose 10 was orally administered each group adult beginning on day 1 continuing through 14. neurotoxin 3-NP induces neurodegenerative, g, neurochemical, pathological alterations animals. Continuous injection according our results, aggravated symptoms suppressing ETC-complex-II, succinate dehydrogenase activity, neurochemical alterations. β-BA, when taken E, improved behavioural such neuromuscular motor impairments, memory cognitive abnormalities. Pharmacological treatments restored ETC complexes enzymes I, II, V levels brain homogenates. treatment also neurotransmitter while lowering inflammatory cytokines oxidative stress biomarkers. β-BA's reducing death supported histopathological findings As result, this research contributed better understanding role natural phytochemicals preventing illnesses HD.

Language: Английский

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Effect of Natural Adenylcyclase/cAMP/CREB Signalling Activator Forskolin against Intra-Striatal 6-OHDA-Lesioned Parkinson’s Rats: Preventing Mitochondrial, Motor and Histopathological Defects

Molecules, Journal Year: 2022, Volume and Issue: 27(22), P. 7951 - 7951

Published: Nov. 17, 2022

Parkinson's disease (PD) is characterised by dopaminergic neuronal loss in the brain area. PD a complex that deteriorates patients' motor and non-motor functions. In experimental animals, neurotoxin 6-OHDA induces neuropathological, behavioural, neurochemical mitochondrial abnormalities formation of free radicals, which related to Parkinson-like symptoms after inter-striatal injection. Pathological manifestations disrupt cAMP/ATP-mediated activity transcription factor CREB, resulting Parkinson's-like symptoms. Forskolin (FSK) direct AC/cAMP/CREB activator isolated from

Language: Английский

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