Positive Effect of α-Asaronol on the Incidence of Post-Stroke Epilepsy for Rat with Cerebral Ischemia-Reperfusion Injury

Jiang, Lan; Hu, Xiangnan

doi:10.3390/molecules27061984

Cited by 9 publications

(2 citation statements)

References 34 publications

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“…These processes are also implicated in neurodegenerative diseases of the CNS such as AD, PD, and others. There is a wealth of evidence suggesting that cerebral ischemia is associated with the development and progression of CNS diseases including ischemic stroke [2], AD [3], PD [4], epilepsy [5], and other [6] related conditions collectively referred to as ischemia-associated CNS diseases [7].…”

Section: Introductionmentioning

confidence: 99%

The Interplay between Mitochondrial Dysfunction and Ferroptosis during Ischemia-Associated Central Nervous System Diseases

Tian,

Huang,

Nie

et al. 2023

Brain Sciences

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Cerebral ischemia, a leading cause of disability and mortality worldwide, triggers a cascade of molecular and cellular pathologies linked to several central nervous system (CNS) disorders. These disorders primarily encompass ischemic stroke, Alzheimer’s disease (AD), Parkinson’s disease (PD), epilepsy, and other CNS conditions. Despite substantial progress in understanding and treating the underlying pathological processes in various neurological diseases, there is still a notable absence of effective therapeutic approaches aimed specifically at mitigating the damage caused by these illnesses. Remarkably, ischemia causes severe damage to cells in ischemia-associated CNS diseases. Cerebral ischemia initiates oxygen and glucose deprivation, which subsequently promotes mitochondrial dysfunction, including mitochondrial permeability transition pore (MPTP) opening, mitophagy dysfunction, and excessive mitochondrial fission, triggering various forms of cell death such as autophagy, apoptosis, as well as ferroptosis. Ferroptosis, a novel type of regulated cell death (RCD), is characterized by iron-dependent accumulation of lethal reactive oxygen species (ROS) and lipid peroxidation. Mitochondrial dysfunction and ferroptosis both play critical roles in the pathogenic progression of ischemia-associated CNS diseases. In recent years, growing evidence has indicated that mitochondrial dysfunction interplays with ferroptosis to aggravate cerebral ischemia injury. However, the potential connections between mitochondrial dysfunction and ferroptosis in cerebral ischemia have not yet been clarified. Thus, we analyzed the underlying mechanism between mitochondrial dysfunction and ferroptosis in ischemia-associated CNS diseases. We also discovered that GSH depletion and GPX4 inactivation cause lipoxygenase activation and calcium influx following cerebral ischemia injury, resulting in MPTP opening and mitochondrial dysfunction. Additionally, dysfunction in mitochondrial electron transport and an imbalanced fusion-to-fission ratio can lead to the accumulation of ROS and iron overload, which further contribute to the occurrence of ferroptosis. This creates a vicious cycle that continuously worsens cerebral ischemia injury. In this study, our focus is on exploring the interplay between mitochondrial dysfunction and ferroptosis, which may offer new insights into potential therapeutic approaches for the treatment of ischemia-associated CNS diseases.

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Section: Introductionmentioning

confidence: 99%

The Interplay between Mitochondrial Dysfunction and Ferroptosis during Ischemia-Associated Central Nervous System Diseases

Tian,

Huang,

Nie

et al. 2023

Brain Sciences

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“…In our series of studies over the last decade on α-asaronol (( E )-3′-hydroxyasarone), it has been demonstrated to exhibit promising pharmaceutical effects including anticonvulsant and antiepileptic activities with lower biotoxicity compared to the two current common antiseizure drugs of α-asarone and carbamazepine. − The in vitro evaluation of α-asaronol on cell viability and neuroprotective activity also revealed a potential protective effect on neuronal oxidative stress . At the same time, further research was conducted on the molecular mechanisms underlying the antiepileptic effects of α-asaronol.…”

Section: Introductionmentioning

confidence: 99%

Pilot-Scale Synthesis and Purification of α-Asaronol for Antiepileptic Drug Development

Zhang

Ouyang

Zhou

et al. 2023

Org. Process Res. Dev.

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A simple and efficient pilot-scale process was developed for the synthesis and purification of α-asaronol ((E)-3′hydroxyasarone). 4.29 kg of α-asaronol 4 (purity 99.92%) was produced in one batch, starting with 2,4,5-trimethoxybenzaldehyde 1 and ethyl hydrogen malonate 2 as raw materials to form intermediate ethyl (E)-3-(2,4,5-trimethoxyphenyl)acrylate 3 (yield 93.3%) by the Knoevenagel condensation reaction, which was then reduced by diisobutylaluminum hydride to produce α-asaronol 4 with a yield of 89.2%. Liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR) spectroscopy analysis revealed four major impurities in the synthesis process, namely, (2,4,5-trimethoxyphenyl)methanol, 3-(2,4,5-trimethoxyphenyl)propan-1-ol, 5,5′-((1E,1′E)-oxybis(prop-1-ene-3,1-diyl)) bis(1,2,4-trimethoxybenzene), and diethyl 2-(2,4,5-trimethoxybenzyl)malonate. By adapting a commonly used recrystallization process through optimization, a large-scale purification method was developed for the purification of α-asaronol, achieving a purity of 99.92% by recrystallization. The pilot study lays the groundwork for the large-scale, high-yield, and high-purity preparation of the candidate drug.

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An update on the role of Hippo signaling pathway in ischemia-associated central nervous system diseases

Xuan¹,

Huang²,

Liu³

et al. 2023

Biomedicine & Pharmacotherapy

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Positive Effect of α-Asaronol on the Incidence of Post-Stroke Epilepsy for Rat with Cerebral Ischemia-Reperfusion Injury

Cited by 9 publications

References 34 publications

The Interplay between Mitochondrial Dysfunction and Ferroptosis during Ischemia-Associated Central Nervous System Diseases

The Interplay between Mitochondrial Dysfunction and Ferroptosis during Ischemia-Associated Central Nervous System Diseases

Pilot-Scale Synthesis and Purification of α-Asaronol for Antiepileptic Drug Development

An update on the role of Hippo signaling pathway in ischemia-associated central nervous system diseases

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