Anti-Zn2+-Toxicity of 4-Hydroxybenzyl Alcohol in Astrocytes and Neurons Contribute to a Robust Neuroprotective Effects in the Postischemic Brain

doi:10.1007/s10571-017-0508-y

Paper

Anti-Zn2+-Toxicity of 4-Hydroxybenzyl Alcohol in Astrocytes and Neurons Contribute to a Robust Neuroprotective Effects in the Postischemic Brain

Published Jun 12, 2017 · Lidan Luo, Seung‐Woo Kim, Hye-Kyung Lee

Cellular and Molecular Neurobiology

Q1 SJR score

15

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0

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Abstract

Abstract4-Hydroxybenzyl alcohol (4-HBA) is an important phenolic constituent of Gastrodia elata (GE) Blume, which is used as a traditional herbal medicine in East Asia. Many activities have been reported to underlie the beneficial effects of 4-HBA in brain, such as, anti-oxidative, anti-inflammatory, anti-excitotoxic, and anti-apoptotic effects in neurons and microglia. Here, the authors demonstrate the robust neuroprotective effects of 4-HBA in rat middle cerebral artery occlusion (MCAO) model of stroke, and showed anti-Zn2+ toxicity in neurons and astrocytes as a molecular mechanism contributing to these effects. Intraperitoneal administration of 4-HBA (20 mg/kg) in Sprague–Dawley rats 1 h after MCAO reduced infarct volumes to 27.1 ± 9.2% of that of MCAO controls and significantly ameliorated motor impairments and neurological deficits. Significant suppressions of Zn2+-induced cell death, ROS generation, and PARP-1 induction by 4-HBA were observed in primary cortical cultures. 4-HBA also protected astrocytes from Zn2+-induced toxicity and suppressing ROS generation by employing slightly different molecular mechanisms, i.e., suppressing PARP-1 induction and NAD depletion under acute Zn2+-treatment and suppressing p67 NADPH oxidase subunit induction under chronic Zn2+-treatment. Results indicate that the protective effects of 4-HBA against Zn2+-toxicity in neurons and astrocytes contribute to its robust neuroprotective effects in the postischemic brain. Considering the pleiotropic effects of 4-HBA, which have been reported in previous reports and added in the present study, it has therapeutic potential for the amelioration of ischemic brain damage.

Non-RCT

Animal Study

Rigorous Journal

Study Snapshot

4-HBA has robust neuroprotective effects in the postischemic brain, with its anti-Zn2+ toxicity in neurons and astrocytes contributing to its protective effects.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Paper

Anti-Zn2+-Toxicity of 4-Hydroxybenzyl Alcohol in Astrocytes and Neurons Contribute to a Robust Neuroprotective Effects in the Postischemic Brain

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References

Neuropharmacological Potential of Gastrodia elata Blume and Its Components

Gastrodia elata Blume rhizome extract and its components show neuroprotective potential by inhibiting oxidative stress and inflammation in preclinical brain injury models.

4-Hydroxybenzyl-substituted amino acid derivatives from Gastrodia elata

New 4-hydroxybenzyl-substituted amino acid derivatives were isolated from Gastrodia elata rhizomes, with one showing potential anti-Fe2+-cysteine activity.

4-hydroxybenzyl alcohol: a novel inhibitor of tumor angiogenesis and growth.

HBA shows potential as an anti-angiogenic treatment for cancer therapy by reducing tumor cell viability, invasiveness, and vascularization without affecting normal animal behavior.

Zinc Promotes the Death of Hypoxic Astrocytes by Upregulating Hypoxia‐Induced Hypoxia‐Inducible Factor‐1alpha Expression via Poly(ADP‐ribose) Polymerase‐1

High intracellular zinc concentrations contribute to cell death in hypoxic astrocytes by modifying PARP-1 and HIF-1, leading to increased cell death during ischemia.

4-Hydroxybenzyl Alcohol Confers Neuroprotection Through Up-Regulation of Antioxidant Protein Expression

4-HBA protects neurons against cerebral ischemic injury by upregulating antioxidant protein expression through the PI3K/Akt pathway.

Citations

The traditional uses, phytochemistry and pharmacology of Gastrodia elata Blume: A comprehensive review

Gastrodia elata Blume is a potentially medicinal and edible plant with diverse pharmacological activities, but its utilization in the pharmaceutical and food industries remains suboptimal.

Mechanism of P-Hydroxy Benzyl Alcohol Against Cerebral Ischemia Based on Metabonomics Analysis

HBA protects neurons and improves cognitive impairment in cerebral ischemia patients by regulating key metabolites and signaling pathways, offering a new molecular target for treatment.

Metabolomics-Based Study of the Protective Effect of 4-Hydroxybenzyl Alcohol on Ischemic Astrocytes

4HBA is a potent neuroprotective agent against ischemic stroke, enhancing astrocyte survival and function while stabilizing the blood-brain barrier through activation of the N-methyl-D-aspartate/p-cAMP-response element binding protein/brain-derived neuro

Taurine Chloramine-Mediated Nrf2 Activation and HO-1 Induction Confer Protective Effects in Astrocytes

Taurine chloramine (Tau-Cl) protects astrocytes by disrupting the Keap1-Nrf2 complex and promoting the transcription of antioxidant genes, potentially offering protection against brain infections and injuries.

Therapeutic application of natural products: NAD+ metabolism as potential target.

Natural products targeting NAD+ metabolism show potential in preventing and treating various diseases, with safe and tolerable effects in various studies and clinical trials.