Honokiol alleviated neurodegeneration by reducing oxidative stress and improving mitochondrial function in mutant SOD1 cellular and mouse models of amyotrophic lateral sclerosis

Zhou, Yujun; Tang, Jingshu; Lan, Jiaqi; Zhong, Yanfei; Wang, Hongyue; Chen, Qiuyu; Kang, Yuying; Sun, Yang; Xu, Feng; Wu, Lei; Jin, Hongtao; Chen, Shizhong; Peng, Ying

doi:10.1016/j.apsb.2022.07.019

Cited by 25 publications

(16 citation statements)

References 89 publications

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“…SOD1-G93A transgenic mice are characterized by expressed G93A mutant form of hSOD1 suitable for neuromuscular disorder studies. Honokiol has been shown to extend the lifespan of SOD1-G93A transgenic mice and improve their motor function and the viability of neuroblastoma/spinal cord NSC-34 hybrid cell lines and the morphology of mitochondria in SOD1-G93A cells (Zhou et al 2023 ). Honokiol can promote cell viability and endoplasmic reticulum stress modulation by SIRT1 expression (Khatoon et al 2022 ).…”

Section: Oxidative Stress Diseases Aging and Antioxidant Interventionsmentioning

confidence: 99%

Reactive oxygen species, toxicity, oxidative stress, and antioxidants: chronic diseases and aging

Jomova,

Raptova,

Alomar

et al. 2023

Arch Toxicol

314

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A physiological level of oxygen/nitrogen free radicals and non-radical reactive species (collectively known as ROS/RNS) is termed oxidative eustress or “good stress” and is characterized by low to mild levels of oxidants involved in the regulation of various biochemical transformations such as carboxylation, hydroxylation, peroxidation, or modulation of signal transduction pathways such as Nuclear factor-κB (NF-κB), Mitogen-activated protein kinase (MAPK) cascade, phosphoinositide-3-kinase, nuclear factor erythroid 2–related factor 2 (Nrf2) and other processes. Increased levels of ROS/RNS, generated from both endogenous (mitochondria, NADPH oxidases) and/or exogenous sources (radiation, certain drugs, foods, cigarette smoking, pollution) result in a harmful condition termed oxidative stress (“bad stress”). Although it is widely accepted, that many chronic diseases are multifactorial in origin, they share oxidative stress as a common denominator. Here we review the importance of oxidative stress and the mechanisms through which oxidative stress contributes to the pathological states of an organism. Attention is focused on the chemistry of ROS and RNS (e.g. superoxide radical, hydrogen peroxide, hydroxyl radicals, peroxyl radicals, nitric oxide, peroxynitrite), and their role in oxidative damage of DNA, proteins, and membrane lipids. Quantitative and qualitative assessment of oxidative stress biomarkers is also discussed. Oxidative stress contributes to the pathology of cancer, cardiovascular diseases, diabetes, neurological disorders (Alzheimer’s and Parkinson’s diseases, Down syndrome), psychiatric diseases (depression, schizophrenia, bipolar disorder), renal disease, lung disease (chronic pulmonary obstruction, lung cancer), and aging. The concerted action of antioxidants to ameliorate the harmful effect of oxidative stress is achieved by antioxidant enzymes (Superoxide dismutases-SODs, catalase, glutathione peroxidase-GPx), and small molecular weight antioxidants (vitamins C and E, flavonoids, carotenoids, melatonin, ergothioneine, and others). Perhaps one of the most effective low molecular weight antioxidants is vitamin E, the first line of defense against the peroxidation of lipids. A promising approach appears to be the use of certain antioxidants (e.g. flavonoids), showing weak prooxidant properties that may boost cellular antioxidant systems and thus act as preventive anticancer agents. Redox metal-based enzyme mimetic compounds as potential pharmaceutical interventions and sirtuins as promising therapeutic targets for age-related diseases and anti-aging strategies are discussed.

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Section: Oxidative Stress Diseases Aging and Antioxidant Interventionsmentioning

confidence: 99%

Reactive oxygen species, toxicity, oxidative stress, and antioxidants: chronic diseases and aging

Jomova,

Raptova,

Alomar

et al. 2023

Arch Toxicol

314

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“…44 Honokiol increased the viability of motor neurons NSC-34 cells in amyotrophic lateral sclerosis disease models both in vitro and in vivo . 45 In the current research, studied concentrations of honokiol resulted in a significant increase in neuron survival after 35 days, when compared to neurons without honokiol. Moreover, it was shown that honokiol exerted no genotoxicity in the iPSC-derived neurons at the concentration of 10 μg/mL.…”

Section: Discussionmentioning

confidence: 77%

Effect of Honokiol on culture time and survival of Alzheimer’s disease iPSC-derived neurons

Le,

Vu,

et al. 2023

Bioimpacts

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Introduction: Patient-derived induced pluripotent stem cells (iPSCs) have been widely used as disease models to test new therapeutic strategies. Moreover, the regenerative potential of stem cells can be improved with the use of biologically active compounds. Our study was designed to explore the effect of honokiol, a small polyphenol molecule extracted from Magnolia officinalis, on the survival and culture time of iPSC-derived neurons from a sporadic Alzheimer’s disease (AD) patient. This study aimed to generate iPSCs from peripheral blood mononuclear cells (PBMCs) of an AD patient using episomal plasmids with a nucleofector system and differentiate them into neurons. These iPSC-derived neurons were used to investigate the effect of honokiol extracted from M. officinalis on their survival and long-term cultures. Methods: IPSCs were generated from PBMCs of an AD patient by introducing Oct-3/4, Sox2, Klf4, L-Myc, and Lin28 using Nucleofector™ Technology. Differentiation of neurons derived from iPSCs was carried out using inducers and recognized by biomarkers. The viability of iPSC-derived neurons with the addition of honokiol extracted from the bark of M. officinalis was determined by the MTT analytical kit. Results: IPSCs were generated by reprogramming AD patient-derived PBMCs and subsequently converted into neurons. The survival and growth of iPSC-derived neurons were significantly enhanced by adding honokiol in the experiment conditions. Conclusion: AD iPSC-derived neurons had a high viability rate when cultured in the presence of honokiol. These results have shown that AD iPSC-derived neurons can be an excellent model for screening neurotrophic agents and improving the conditions for long-term cultures of human iPSC-derived neurons. Honokiol proves to be a potential candidate for cellular therapeutics against neurodegenerative disorders.

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“…G93A is a heavily studied gene mutation of the SOD1 protein that represents a substitution of glycine with alanine from the codon 93 of the SOD1 protein, changing its conformation, and is also responsible for approximately 20% of the familial ALS cases. According to a study conducted by the Chinese Pharmaceutical Association in 2023 [ 147 ], oxidative stress has a major impact on ALS pathology; patients showed different oxidative markers, such as glutamate excitotoxicity, and dysfunctions at several levels, such as mitochondria, due to calcium influx, and axon as well as protein oxidation. These modifications observed were at SOD1-G93A in mice.…”

Section: Amyotrophic Lateral Sclerosis (Als)mentioning

confidence: 99%

“…These modifications observed were at SOD1-G93A in mice. This mutation is relatively rare in the general population but it is very common in familial ALS, and multiple studies on animal models have also shown that having the SOD1-G93A mutation is enough to cause motor-neuron degeneration [ 147 , 148 , 149 ]. Understanding the mechanisms as well as the specific effects of SOD1 mutations on protein structure and functions is an important area of research for developing effective treatments for ALS and neurodegenerative diseases in general.…”

Section: Amyotrophic Lateral Sclerosis (Als)mentioning

confidence: 99%

Unraveling Molecular and Genetic Insights into Neurodegenerative Diseases: Advances in Understanding Alzheimer’s, Parkinson’s, and Huntington’s Diseases and Amyotrophic Lateral Sclerosis

Ciurea,

Mohan,

Covache-Busuioc

et al. 2023

IJMS

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Neurodegenerative diseases are, according to recent studies, one of the main causes of disability and death worldwide. Interest in molecular genetics has started to experience exponential growth thanks to numerous advancements in technology, shifts in the understanding of the disease as a phenomenon, and the change in the perspective regarding gene editing and the advantages of this action. The aim of this paper is to analyze the newest approaches in genetics and molecular sciences regarding four of the most important neurodegenerative disorders: Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis. We intend through this review to focus on the newest treatment, diagnosis, and predictions regarding this large group of diseases, in order to obtain a more accurate analysis and to identify the emerging signs that could lead to a better outcome in order to increase both the quality and the life span of the patient. Moreover, this review could provide evidence of future possible novel therapies that target the specific genes and that could be useful to be taken into consideration when the classical approaches fail to shed light.

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Honokiol alleviated neurodegeneration by reducing oxidative stress and improving mitochondrial function in mutant SOD1 cellular and mouse models of amyotrophic lateral sclerosis

Cited by 25 publications

References 89 publications

Reactive oxygen species, toxicity, oxidative stress, and antioxidants: chronic diseases and aging

Reactive oxygen species, toxicity, oxidative stress, and antioxidants: chronic diseases and aging

Effect of Honokiol on culture time and survival of Alzheimer’s disease iPSC-derived neurons

Unraveling Molecular and Genetic Insights into Neurodegenerative Diseases: Advances in Understanding Alzheimer’s, Parkinson’s, and Huntington’s Diseases and Amyotrophic Lateral Sclerosis

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