Pharmacotherapeutic Potential of Garlic in Age-Related Neurological Disorders

: Age-related neurological disorders [ANDs] involve neurodegenerative diseases [NDDs] such as Alzheimer's disease [AD], the most frequent kind of dementia in elderly people, and Parkinson's disease [PD], and also other disorders like epilepsy and migraine. Although ANDs are multifactorial, Aging is a principal risk factor for them. The common and most main pathologic features among ANDs are inflammation, oxidative stress, and misfolded proteins accumulation. Since failing brains caused by ANDs impose a notable burden on public health and their incidence is increasing, a lot of works has been done to overcome them. Garlic, Allium sativum, has been used for different medical purposes globally and more than thousands of publications have reported its health benefits. Garlic and aged garlic extract are considered potent anti-inflammatory and antioxidants agents and can have remarkable neuroprotective effects. This review is aimed to summarize knowledge on the pharmacotherapeutic potential of garlic and its components in ANDs.

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Neurochemical Effects of 4-(2Chloro-4-Fluorobenzyl)-3-(2-Thienyl)-1,2,4-Oxadiazol-5(4H)-One in the Pentylenetetrazole (PTZ)-Induced Epileptic Seizure Zebrafish Model

International Journal of Molecular Sciences ◽

10.3390/ijms22031285 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1285

Author(s):

Seong Soon Kim ◽

Hyemin Kan ◽

Kyu-Seok Hwang ◽

Jung Yoon Yang ◽

Yuji Son ◽

...

Keyword(s):

Oxidative Stress ◽

Epileptic Seizure ◽

Neurological Disorders ◽

Aminobutyric Acid ◽

Oxygen Species ◽

Gamma Aminobutyric Acid ◽

Zebrafish Model ◽

Neuroprotective Effects ◽

Drug Discovery And Development ◽

Spontaneous Seizures

Epilepsy is one of the most common neurological disorders, and it is characterized by spontaneous seizures. In a previous study, we identified 4-(2-chloro-4-fluorobenzyl)-3-(2-thienyl)-1,2,4-oxadiazol-5(4H)-one (GM-90432) as a novel anti-epileptic agent in chemically- or genetically-induced epileptic zebrafish and mouse models. In this study, we investigated the anti-epileptic effects of GM-90432 through neurochemical profiling-based approach to understand the neuroprotective mechanism in a pentylenetetrazole (PTZ)-induced epileptic seizure zebrafish model. GM-90432 effectively improved PTZ-induced epileptic behaviors via upregulation of 5-hydroxytryptamine, 17-β-estradiol, dihydrotestosterone, progesterone, 5α -dihydroprogesterone, and allopregnanolone levels, and downregulation of normetanephrine, gamma-aminobutyric acid, and cortisol levels in brain tissue. GM-90432 also had a protective effect against PTZ-induced oxidative stress and zebrafish death, suggesting that it exhibits biphasic neuroprotective effects via scavenging of reactive oxygen species and anti-epileptic activities in a zebrafish model. In conclusion, our results suggest that neurochemical profiling study could be used to better understand of anti-epileptic mechanism of GM-90432, potentially leading to new drug discovery and development of anti-seizure agents.

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Coenzyme Q10, Ageing and the Nervous System: An Overview

Antioxidants ◽

10.3390/antiox11010002 ◽

2021 ◽

Vol 11 (1) ◽

pp. 2

Author(s):

David Mantle ◽

Robert A. Heaton ◽

Iain P. Hargreaves

Keyword(s):

Oxidative Stress ◽

Coenzyme Q10 ◽

Neurological Disorders ◽

Neurological Disease ◽

Age Related ◽

Increased Risk ◽

Potential Therapeutic Role ◽

Ageing Brain ◽

And Oxidative Stress

The ageing brain is characterised by changes at the physical, histological, biochemical and physiological levels. This ageing process is associated with an increased risk of developing a number of neurological disorders, notably Alzheimer’s disease and Parkinson’s disease. There is evidence that mitochondrial dysfunction and oxidative stress play a key role in the pathogenesis of such disorders. In this article, we review the potential therapeutic role in these age-related neurological disorders of supplementary coenzyme Q10, a vitamin-like substance of vital importance for normal mitochondrial function and as an antioxidant. This review is concerned primarily with studies in humans rather than in vitro studies or studies in animal models of neurological disease. In particular, the reasons why the outcomes of clinical trials supplementing coenzyme Q10 in these neurological disorders is discussed.

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Low temperature-aged garlic extract suppresses psychological stress by modulation of stress hormones and oxidative stress response in brain

Journal of the Chinese Medical Association ◽

10.1097/jcma.0000000000000028 ◽

2019 ◽

Vol 82 (3) ◽

pp. 191-195 ◽

Cited By ~ 5

Author(s):

Kyung-A Hwang ◽

Yu-Jin Hwang ◽

In-Guk Hwang ◽

Jin Song ◽

Young Jun Kim

Keyword(s):

Oxidative Stress ◽

Stress Response ◽

Low Temperature ◽

Psychological Stress ◽

Stress Hormones ◽

Oxidative Stress Response ◽

Garlic Extract ◽

Aged Garlic Extract ◽

And Oxidative Stress ◽

Aged Garlic

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The Neuroprotective Effects of Astaxanthin: Therapeutic Targets and Clinical Perspective

Molecules ◽

10.3390/molecules24142640 ◽

2019 ◽

Vol 24 (14) ◽

pp. 2640 ◽

Cited By ~ 20

Author(s):

Fakhri ◽

Aneva ◽

Farzaei ◽

Sobarzo-Sánchez

Keyword(s):

Oxidative Stress ◽

Neurodegenerative Disorders ◽

Neurological Disorders ◽

Spinal Cord Injuries ◽

Neurological Diseases ◽

Mechanisms Of Action ◽

Clinical Perspective ◽

Neuroprotective Effects ◽

Brain And Spinal Cord ◽

Neuronal Disorders

As the leading causes of human disability and mortality, neurological diseases affect millions of people worldwide and are on the rise. Although the general roles of several signaling pathways in the pathogenesis of neurodegenerative disorders have so far been identified, the exact pathophysiology of neuronal disorders and their effective treatments have not yet been precisely elucidated. This requires multi-target treatments, which should simultaneously attenuate neuronal inflammation, oxidative stress, and apoptosis. In this regard, astaxanthin (AST) has gained growing interest as a multi-target pharmacological agent against neurological disorders including Parkinson’s disease (PD), Alzheimer’s disease (AD), brain and spinal cord injuries, neuropathic pain (NP), aging, depression, and autism. The present review highlights the neuroprotective effects of AST mainly based on its anti-inflammatory, antioxidative, and anti-apoptotic properties that underlies its pharmacological mechanisms of action to tackle neurodegeneration. The need to develop novel AST delivery systems, including nanoformulations, targeted therapy, and beyond, is also considered.

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Protective effect of aged garlic extract against the oxidative stress induced by cisplatin on blood cells parameters and hepatic antioxidant enzymes in rats

Toxicology Reports ◽

10.1016/j.toxrep.2014.09.003 ◽

2014 ◽

Vol 1 ◽

pp. 682-691 ◽

Cited By ~ 18

Author(s):

Ashraf Y. Nasr

Keyword(s):

Oxidative Stress ◽

Antioxidant Enzymes ◽

Protective Effect ◽

Blood Cells ◽

Garlic Extract ◽

Aged Garlic Extract ◽

Aged Garlic

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The Antioxidant Mechanisms Underlying the Aged Garlic Extract- and S-Allylcysteine-Induced Protection

Oxidative Medicine and Cellular Longevity ◽

10.1155/2012/907162 ◽

2012 ◽

Vol 2012 ◽

pp. 1-16 ◽

Cited By ~ 103

Author(s):

Ana L. Colín-González ◽

Ricardo A. Santana ◽

Carlos A. Silva-Islas ◽

Maria E. Chánez-Cárdenas ◽

Abel Santamaría ◽

...

Keyword(s):

Oxidative Stress ◽

Molecular Mechanisms ◽

Original Data ◽

Garlic Extract ◽

Protective Effects ◽

Aged Garlic Extract ◽

Antioxidant Mechanisms ◽

Aged Garlic

Aged garlic extract (AGE) is an odorless garlic preparation containing S-allylcysteine (SAC) as its most abundant compound. A large number of studies have demonstrated the antioxidant activity of AGE and SAC in bothin vivo—in diverse experimental animal models associated to oxidative stress—andin vitroconditions—using several methods to scavenge reactive oxygen species or to induce oxidative damage. Derived from these experiments, the protective effects of AGE and SAC have been associated with the prevention or amelioration of oxidative stress. In this work, we reviewed different antioxidant mechanisms (scavenging of free radicals and prooxidant species, induction of antioxidant enzymes, activation of Nrf2 factor, inhibition of prooxidant enzymes, and chelating effects) involved in the protective actions of AGE and SAC, thereby emphasizing their potential use as therapeutic agents. In addition, we highlight the ability of SAC to activate Nrf2 factor—a master regulator of the cellular redox state. Here, we include original data showing the ability of SAC to activate Nrf2 factor in cerebral cortex. Therefore, we conclude that the therapeutic properties of these molecules comprise cellular and molecular mechanisms at different levels.

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UJI EFEK AGED GARLIC EXTRACT (Allium sativum L) TERHADAP WAKTU PERDARAHAN MENCIT PUTIH JANTAN

Jurnal Kedokteran Syiah Kuala ◽

10.24815/jks.v18i1.11205 ◽

2018 ◽

Vol 18 (1) ◽

Author(s):

Fajar Sartika Hadi

Keyword(s):

Platelet Aggregation ◽

Allium Sativum ◽

Bleeding Time ◽

Garlic Extract ◽

Oral Suspension ◽

Control Group ◽

Aged Garlic Extract ◽

Post Test ◽

Mean Time ◽

Aged Garlic

Abstrak. Bawang putih (Allium sativum L) telah digunakan untuk mengobati penyakit sejak ribuan tahun yang lalu seperti hipertensi, infeksi dan bekas gigitan ular.Saat ini, preparat bawang putih yang dikenal sebagai Aged Garlic Extract banyak diteliti dalam mengevaluasi efek kardioprotektif penyusunnya yaitu S-allylcysteine (SAC).Penelitian ini bertujuan untuk mengetahui potensi SAC dalam menghambat agregasi trombosit melalui pengamatan waktu perdarahan. Penelitian ini dirancang sebagai laboratorium eksperimental dengan rancangan kelompokPre Test-Post Test secara acak yang dilakukan pada 30 ekor tikus jantan yang terbagi dalam lima kelompok. Perlakuan diberikan pada hari ke 8 sampai hari ke 21, yaitu kelompok K1 (kontrol negatif), kelompok K2 (Clopidogrel Oral Suspension dosis 0,195 mg / 20 g BB), kelompok P1 (Aged Garlic Extract dosis 1 mg / 20 g BB) , kelompok P2 (AGE dosis 2 mg / 20 g BB), kelompok P3 (AGE dosis 4 mg / 20 g BB). Pengukuran waktu perdarahan dilakukan pada hari ke 0 dan 21.Analisis data menggunakan Uji Normalitas Saphiro-Wilk, Uji Kruskal-Wallis, dan Uji Mann-Whitney. Hasil penelitian ini dengan uji t-paired menunjukkan bahwa tidak ada perubahan signifikan dalam rerata waktu perdarahan pada kelompok K1 (p = 0,988), K2 (p = 0,096), P2 (0,053) dan P3 (0,335), sedangkan kelompok P1 menunjukkan perubahan waktu perdarahan dengan nilai signifikansi p = 0,034. Uji Kruskal-Wallis setelah perlakuan dan uji Mann-Whitney menunjukkan bahwa hanya ada perbedaan yang signifikan antara kelompok K2 dan kelompok P1, P2 (p 0,05). Berdasarkan hasil penelitian ini menunjukkan bahwa Aged Garlic Extract tidak memperpanjang waktu perdarahan.Kata kunci: Abstract. Garlic (Allium sativum L) has been used for thousands of years to treat many conditions, including hypertension, infections, and snakebites. Currently, garlic preparation named Aged Garlic Extract is widely use to evaluates the cardioprotective effect of its constituent S-allylcysteine (SAC). This study aims to determine the potential of SAC in inhibiting platelet aggregation through observation time of bleeding. This research is designed as a laboratorium experimental with randomized Pre-Test Post Test Control Group Design that conducted on 30 male mice divided into five groups. The treatment was given on the 8th day until the 21st day, ie group K1 (negative control), group K2 (Clopidogrel Oral Suspension dose 0,195 mg/20 g BB), group P1 (Aged Garlic Extract dose 1 mg/ 20 g BB), group P2 (Aged Garlic Extract dose 2 mg/ 20 g BB), group P3 (Aged Garlic Extract dose 4 mg/20 g BB). The measurement of bleeding time on day 0 and 21. Data analysis used Saphiro-Wilk Normality Test, t-paired, Kruskal-Wallis Test, and Mann-Whitney Test.The results of this study with t-paired test showed that there was no significant change in mean time of bleeding in groups K1 (p=0,988), K2 (p=0,096), P2 (0,053) and P3 (0,335) , while P1 group showed a significant mean time change in bleeding time with value of significance is p= 0,034. Kruskal-Wallis test after treatment and Mann-Whitney test showed that there were only significant differences between group K2 and group P1,P2 (p0,05). Based on the result of this study show that Aged Garlic Extract doesn’t prolong the bleeding time. Key words : Aged Garlic Extract, bleeding time, platelet aggregation

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Autophagy Upregulation by the TFEB Inducer Trehalose Protects against Oxidative Damage and Cell Death Associated with NRF2 Inhibition in Human RPE Cells

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/5296341 ◽

2020 ◽

Vol 2020 ◽

pp. 1-18

Author(s):

Samuel Abokyi ◽

Sze wan Shan ◽

Chi-ho To ◽

Henry Ho-lung Chan ◽

Dennis Yan-yin Tse

Keyword(s):

Oxidative Stress ◽

Oxidative Damage ◽

Retinal Pigment ◽

Age Related Macular Degeneration ◽

Mrna Levels ◽

Neuroprotective Effects ◽

Rpe Cells ◽

Age Related ◽

Protein Expressions

Trehalose is a natural dietary molecule that has shown antiaging and neuroprotective effects in several animal models of neurodegenerative diseases. The role of trehalose in the management of age-related macular degeneration (AMD) is yet to be investigated and whether trehalose could be a remedy for the treatment of diseases linked to oxidative stress and NRF2 dysregulation. Here, we showed that incubation of human retinal pigment epithelial (RPE) cells with trehalose enhanced the mRNA and protein expressions of TFEB, autophagy genes ATG5 and ATG7, as well as protein expressions of macroautophagy markers, LC3B and p62/SQTM1, and the chaperone-mediated autophagy (CMA) receptor LAMP2. Cathepsin D, a hydrolytic lysosomal enzyme, was also increased by trehalose, indicating higher proteolytic activity. Moreover, trehalose upregulated autophagy flux evident by an increase in the endogenous LC3B level, and accumulation of GFP-LC3B puncta and free GFP fragments in GFP-LC3 ̶ expressing cells in the presence of chloroquine. In addition, the mRNA levels of key molecular targets implicated in RPE damage and AMD, such as vascular endothelial growth factor- (VEGF-) A and heat shock protein 27 (HSP27), were downregulated, whereas NRF2 was upregulated by trehalose. Subsequently, we mimicked in vitro AMD conditions using hydroquinone (HQ) as the oxidative insult on RPE cells and evaluated the cytoprotective effect of trehalose compared to vehicle treatment. HQ depleted NRF2, increased oxidative stress, and reduced the viability of cells, while trehalose pretreatment protected against HQ-induced toxicity. The cytoprotection by trehalose was dependent on autophagy but not NRF2 activation, since autophagy inhibition by shRNA knockdown of ATG5 led to a loss of the protective effect. The results support the transcriptional upregulation of TFEB and autophagy by trehalose and its protection against HQ-induced oxidative damage in RPE cells. Further investigation is, therefore, warranted into the therapeutic value of trehalose in alleviating AMD and retinal diseases associated with impaired NRF2 antioxidant defense.

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Flavonoid-Rich Ethanol Extract from the Leaves of Diospyros kaki Attenuates D-Galactose-Induced Oxidative Stress and Neuroinflammation-Mediated Brain Aging in Mice

Oxidative Medicine and Cellular Longevity ◽

10.1155/2018/8938207 ◽

2018 ◽

Vol 2018 ◽

pp. 1-12 ◽

Cited By ~ 13

Author(s):

Yingjuan Ma ◽

Bin Ma ◽

Yuying Shang ◽

Qingqing Yin ◽

Dejie Wang ◽

...

Keyword(s):

Oxidative Stress ◽

Neurodegenerative Diseases ◽

Nuclear Translocation ◽

Brain Aging ◽

Ethanol Extract ◽

Neurological Impairment ◽

Diospyros Kaki ◽

Neuroprotective Effects ◽

Age Related ◽

Y Maze

Aging is a major factor that contributes to neurological impairment and neuropathological changes, such as inflammation, oxidative stress, neuronal apoptosis, and synaptic dysfunction. Flavonoids act as protective antioxidant and anti-inflammatory agents against various age-related neurodegenerative diseases. Here, we investigated the protective effect and mechanisms of the flavonoid-rich ethanol extract from the leaves of Diospyros kaki (FELDK) in the cortex and hippocampus of D-galactose- (gal-) aged mice. Our results showed that FELDK treatment restored memory impairment in mice as determined by the Y-maze and Morris water maze tests. FELDK decreased oxidative stress levels via inhibiting reactive oxygen species (ROS) and malondialdehyde (MDA) production and elevating antioxidative enzymes. FELDK also alleviated D-gal-induced neuroinflammation via suppressing the expression of advanced glycation end products (AGEs) and receptor for AGEs (RAGE) and activating microgliosis and astrocytosis, nuclear factor kappa B (NF-κB) nuclear translocation, and downstream inflammatory mediators. Moreover, FELDK inhibited the phosphatidylinositol 3-kinase (PI3K)/Akt and C-jun N-terminal kinase (JNK) apoptotic signaling pathways and ameliorated the impairment of synapse-related proteins. Hence, these results indicate that FELDK exerts neuroprotective effects on D-gal-induced brain aging. Thus, FELDK may be a potential therapeutic strategy for preventing and treating age-related neurodegenerative diseases such as Alzheimer’s disease.

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