Catechol protects against iron-mediated oxidative brain injury by restoring antioxidative metabolic pathways; and modulation of purinergic and cholinergic enzymes activities

Salau, Veronica F.; Erukainure, Ochuko L.; Koorbanally, Neil A.; Islam, Shahidul

doi:10.1111/jphp.13352

Cited by 3 publications

(1 citation statement)

References 47 publications

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“…Reduced glutathione assay (GSH): For estimation of the reduced glutathione levels, the proteins were precipitated in 1000 µL of brain homogenate mixed with equal parts of 4% sulfosalicylic acid solution according to the method previously reported [28]. The reaction mixture was incubated at 4 • C for 1 h, then centrifuged for 20 min at 4 • C and 1200× g. The reaction mixture contained 2700 µL 0.1 M phosphate buffer of pH 7.4, 100 µL centrifuged aliquot and 200 µL (100 mM) DTNB solution.…”

Section: Antioxidant Enzyme Profiling Of Brain Homogenatesmentioning

confidence: 99%

Friedelin Attenuates Neuronal Dysfunction and Memory Impairment by Inhibition of the Activated JNK/NF-κB Signalling Pathway in Scopolamine-Induced Mice Model of Neurodegeneration

et al. 2022

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Oxidative stress (OS) and c-Jun N-terminal kinase (JNK) are both key indicators implicated in neuro-inflammatory signalling pathways and their respective neurodegenerative diseases. Drugs targeting these factors can be considered as suitable candidates for treatment of neuronal dysfunction and memory impairment. The present study encompasses beneficial effects of a naturally occurring triterpenoid, friedelin, against scopolamine-induced oxidative stress and neurodegenerative pathologies in mice models. The treated animals were subjected to behavioural tests i.e., Y-maze and Morris water maze (MWM) for memory dysfunction. The underlying mechanism was determined via western blotting, antioxidant enzymes and lipid profile analyses. Molecular docking studies were carried out to predict the binding modes of friedelin in the binding pocket of p-JNK protein. The results reveal that scopolamine caused oxidative stress by (1) inhibiting catalase (CAT), peroxidase enzyme (POD), superoxide dismutase (SOD), and reduced glutathione enzyme (GSH); (2) the up-regulation of thiobarbituric acid reactive substances (TBARS) in mice brain; and (3) affecting the neuronal synapse (both pre- and post-synapse) followed by associated memory dysfunction. In contrast, friedelin administration not only abolished scopolamine-induced oxidative stress, glial cell activation, and neuro-inflammation but also inhibited p-JNK and NF-κB and their downstream signaling molecules. Moreover, friedelin administration improved neuronal synapse and reversed scopolamine-induced memory impairment accompanied by the inhibition of β-secretase enzyme (BACE-1) to halt amyloidogenic pathways of amyloid-β production. In summary, all of the results show that friedelin is a potent naturally isolated neuro-therapeutic agent to reverse scopolamine-induced neuropathology, which is characteristic of Alzheimer’s disease.

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Section: Antioxidant Enzyme Profiling Of Brain Homogenatesmentioning

confidence: 99%

Friedelin Attenuates Neuronal Dysfunction and Memory Impairment by Inhibition of the Activated JNK/NF-κB Signalling Pathway in Scopolamine-Induced Mice Model of Neurodegeneration

et al. 2022

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A phytoconstituent 6-aminoflavone ameliorates lipopolysaccharide-induced oxidative stress mediated synapse and memory dysfunction via p-Akt/NF-kB pathway in albino mice

et al. 2023

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The current work examined the therapeutic potential of 6-aminoflavone (6AF) against mouse model-based oxidative stress-driven synaptic and memory impairment caused by lipopolysaccharides (LPSs). In the brains of the experimental mice, LPS administration for 3 weeks significantly increased oxidative stress by inhibiting antioxidant enzymes, including superoxide dismutase, peroxidase, catalase, glutathione, and upregulating lipid peroxidase. Male albino mice were arbitrarily divided into four groups including (1) Control, (2) LPS treated (250 µg/kg, for 3 weeks), (3) LPS plus 6AF treated (30 mg/kg for 2 weeks), and (4) 6AF treated (30 mg/kg for 2 weeks). Different antioxidant enzyme assays, behavior tasks, and the western blotting technique were used to test the therapeutic potentials of this 6AF. Remarkably, the dosage of 6AF significantly reversed the activities of antioxidant enzymes and reduced neuroinflammation in adult albino mice. Additionally, 6HF also improved the synapse (both pre- and post-proteins) and restored the impaired memory against LPS. In short, these findings propose that 6AF is a natural, non-toxic, and potent therapeutic agent to treat neurodegenerative diseases.

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Metabolomic analysis and pharmacological validation of the cerebral protective effect of 3,4‑dihydroxybenzaldehyde on cerebral ischemia‑reperfusion injury

et al. 2022

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3,, one of the active components of Gastrodia elata, has a cerebral protective effect and can effectively combat cerebral ischemia/reperfusion (I/R) injury in rats. However, the metabolite profiles and underlying mechanisms associated with dBd remain unclear. To explore the level of energy metabolism and pharmacological targets in brain tissue following dBd treatment of stroke. The right middle cerebral artery of the rats was occluded for 2 h and reperfused for 24 h to simulate brain i/r injury. Pharmacological results showed that dBd reduced cerebral infarct volume, improved neurological function and increased adenosine triphosphate (aTP) content. Mitochondria are the primary sites for aTP generation and cellular energy supply and decreasing mitochondrial dysfunction can alleviate the energy expenditure of ischemic stroke. Through further experiments, it was found that mitochondrial damage was recovered following dBd treatment, which was manifested by the improvement of mitochondrial morphology under an electron microscope and the reduction of oxidative stress damage. The metabolomics of middle cerebral artery occlusion/reperfusion (Mcao/r) rat brain tissue was studied by the liquid chromatography-tandem mass spectrometry metabolomics method. Significantly different metabolites were screened and the pathways involved included amino sugar and nucleotide sugar metabolism and pentose phosphate pathway. Finally, the present study performed targeted metabolic profiling and validated potential therapeutic targets. uridine diphosphate n-acetylglucosamine (udP-Glcnac) levels were decreased in the Mcao/r group but significantly increased in the DBD group. TdT-mediated duTP nick end labeling (Tunel) staining, hematoxylin and eosin staining and western blotting showed that brain cell apoptosis was inhibited and neuronal morphology improved. among them, the regulatory enzyme o-Glcnac transferase (OGT) of UDP-GlcNAc appeared to be significantly increased and neuronal apoptosis was inhibited following dBd treatment, which was verified by western blotting. Therefore, by analyzing mitochondrial dysfunction following i/r and the characterization of potential markers in mitochondrial energy metabolism, it was shown that oGT could inhibit neuronal apoptosis as a potential therapeutic target for brain i/r injury.

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Catechol protects against iron-mediated oxidative brain injury by restoring antioxidative metabolic pathways; and modulation of purinergic and cholinergic enzymes activities

Cited by 3 publications

References 47 publications

Friedelin Attenuates Neuronal Dysfunction and Memory Impairment by Inhibition of the Activated JNK/NF-κB Signalling Pathway in Scopolamine-Induced Mice Model of Neurodegeneration

Friedelin Attenuates Neuronal Dysfunction and Memory Impairment by Inhibition of the Activated JNK/NF-κB Signalling Pathway in Scopolamine-Induced Mice Model of Neurodegeneration

A phytoconstituent 6-aminoflavone ameliorates lipopolysaccharide-induced oxidative stress mediated synapse and memory dysfunction via p-Akt/NF-kB pathway in albino mice

Metabolomic analysis and pharmacological validation of the cerebral protective effect of 3,4‑dihydroxybenzaldehyde on cerebral ischemia‑reperfusion injury

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