Novel α-Lipoic Acid/3-n-Butylphthalide Conjugate Enhances Protective Effects against Oxidative Stress and 6-OHDA Induced Neuronal Damage
| Autor: | Sopana Jamornwan, Sheng-Biao Wan, Chotchanit Sunrat, Kai-Rui Yue, Erik W. Dent, Kwanchanok Uppakara, Liang-Xing Duan, Witchuda Saengsawang |
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| Rok vydání: | 2020 |
| Předmět: |
0303 health sciences
Parkinson's disease Antioxidant Physiology Chemistry Cognitive Neuroscience medicine.medical_treatment Neurodegeneration Cell Biology General Medicine Glutathione Mitochondrion Pharmacology medicine.disease medicine.disease_cause Biochemistry Neuroprotection 03 medical and health sciences Lipoic acid chemistry.chemical_compound 0302 clinical medicine medicine 030217 neurology & neurosurgery Oxidative stress 030304 developmental biology |
| Zdroj: | ACS Chemical Neuroscience. 11:1634-1642 |
| ISSN: | 1948-7193 |
| DOI: | 10.1021/acschemneuro.0c00105 |
| Popis: | Neurodegenerative diseases are irreversible conditions that result in progressive degeneration and death of nerve cells. Although the underlying mechanisms may vary, oxidative stress is considered to be one of the major causes of neuronal loss. Importantly, there are still no comprehensive treatments to completely cure these diseases. Therefore, protecting neurons from oxidative damage may be the most effective therapeutic strategy. Here we report a neuroprotective effects of a novel hybrid compound (dlx-23), obtained by conjugating α-lipoic acid (ALA), a natural antioxidant agent, and 3-n-butylphthalide (NBP), a clinical anti-ischemic drug. Dlx-23 protected against neuronal death induced by both H2O2 induced oxidative stress in Cath.-a-differentiated (CAD) cells and 6-OHDA, a toxin model of Parkinson's disease (PD) in SH-SY5Y cells. These activities proved to be more potent than the parent compound (ALA) alone. Dlx-23 scavenged free radicals, increased glutathione levels, and prevented mitochondria damage. In addition, live imaging of primary cortical neurons demonstrated that dlx-23 protected against neuronal growth cone damage induced by H2O2. Taken together these results suggest that dlx-23 has substantial potential to be further developed into a novel neuroprotective agent against oxidative damage and toxin induced neurodegeneration. |
| Databáze: | OpenAIRE |
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