Proteomic Analysis of the Effects of Aged Garlic Extract and Its FruArg Component on Lipopolysaccharide-Induced Neuroinflammatory Response in Microglial Cells

Zhou, Hui; Qu, Zhe; Mossine, Valeri V.; Nknolise, Dineo L.; Li, Jilong; Chen, Zhenzhou; Cheng, Jianlin; Greenlief, C. Michael; Mawhinney, Thomas P.; Brown, Paula N.; Fritsche, Kevin L.; Hannink, Mark; Lubahn, Dennis B.; Sun, Grace Y.; Z, Gu

doi:10.1371/journal.pone.0113531

Cited by 29 publications

(28 citation statements)

References 53 publications

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“…Nitrosative stress elicited by NO and RNS has been implicated in the pathogenesis of neurodegenerative diseases, such as AD, Parkinson's disease and traumatic brain injury (TBI) (47-52). Previous studies by our group demonstrated that AGE can attenuate NO production in microglial BV-2 cells (20,21). Specifically, treatment with AGE (0.1-1%) or FruArg (2-5 mM) for 20 h was found to significantly reduce NO production in a dose-dependent manner in BV2 cells against LPS-induced neuroinflammation (20).…”

Section: Neuroprotective Effects Of Agementioning

confidence: 79%

“…Previous studies by our group also demonstrated the ability of both AGE and FruArg to reduce nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated murine microglial BV-2 cells in a concentration-dependent manner (20,21). Subsequently, we applied quantitative proteomic analysis by two-dimensional differential in-gel electrophoresis (2D-DIGE) integrated with liquid chromatography tandem mass spectrometry (LC-MS/MS) to profile the proteome patterns and to determine the effects of AGE and FruArg on LPS-stimulated BV-2 cells (20). Furthermore, we investigated gene regulation and associated signaling pathways using the RNA-sequencing (RNA-Seq) approach coupled with machine learning based bioinformatics analysis (21).…”

Section: Bioactive Components From Garlic On Brain Resiliency Againstmentioning

confidence: 86%

“…AGE has also been found to alleviate oxidative stress by scavenging ROS, inhibiting LDL oxidation, enhancing antioxidant signaling [such as superoxide dismutase (SOD), glutathione peroxidase (GPX) and glutathione (GSH)] and mitigating lipid peroxidation [malondialdehyde (MDA)] (41-45). Our previous study also demonstrated the protective effects of AGE on ROS and NO production from L-arginine by NO synthase (NOS) (20). Excessive NO can undergo oxidative-reductive reactions and cause cellular damage by endangering reactive nitrogen species (RNS) (46).…”

Section: Neuroprotective Effects Of Agementioning

confidence: 94%

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Bioactive components from garlic on brain resiliency against neuroinflammation and neurodegeneration (Review)

et al. 2019

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Garlic (Allium sativum) has been widely used for culinary and medicinal purposes. Aged garlic extract (AGE) and sulfur-containing compounds, including S-allylcysteine (SAC) are well documented botanical active components of garlic. AGE is prepared by the prolonged extraction of fresh garlic with aqueous ethanol and is considered a nutritional supplement with potential to promote human health. SAC is a water-soluble organosulfur compound and the most abundant component of AGE. Studies have demonstrated that both AGE and SAC can exert neuroprotective effects against neuroinflammation and neurodegeneration. Another bioactive component in AGE is N-α-(1-deoxy-D-fructos-1-yl)-L-a rginine (FruArg) although less is known about the metabolic activity of this compound. The main aim of this review was to provide an undated overview of the neuroprotective perspectives of these active garlic components (AGE, SAC and FruArg). Of interest, our studies and those of others indicate that both AGE and FruArg are involved in the regulation of gene transcription and protein expression. AGE has been shown to reverse 67% of the transcriptome alteration induced by endotoxins-lipopolysaccharide (LPS), and FruArg has been shown to account for the protective effects by reversing 55% of genes altered in a cell-based neuroinflammation paradigm stimulated by LPS in murine BV-2 microglial cells. AGE and FruArg can alleviate neuroinflammatory responses through a variety of signaling pathways, such as Toll-like receptor and interleukin (IL)-6 signaling, as well as by upregulating the nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated oxidative stress pathways known to promote microglial resiliency against neuroinflammation and neurodegeneration. The capability of FruArg to pass through the blood-brain barrier further supports its potential as a therapeutic compound. In summary, these experimental results provide new insight into the understanding of the neuroprotective effects of garlic components in promoting brain resiliency for health benefits.

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Section: Neuroprotective Effects Of Agementioning

confidence: 79%

Section: Bioactive Components From Garlic On Brain Resiliency Againstmentioning

confidence: 86%

Section: Neuroprotective Effects Of Agementioning

confidence: 94%

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Bioactive components from garlic on brain resiliency against neuroinflammation and neurodegeneration (Review)

et al. 2019

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“…Z-ajoene from garlic exerted neuroprotective effects by reducing lipid peroxidation and antioxidant or anti-inflammatory activities [37]. A few other clinically proven neuroprotective agents from garlic are S-propargylcysteine and S-methyl cysteine and N-α-(1-deoxy-D-fructos-1yl)-L-arginine [38,39].…”

Section: Neuroprotective Effectmentioning

confidence: 99%

Bioactivities of Allicin and Related Organosulfur Compounds from Garlic: Overview of the Literature Since 2010

Mandal¹,

Das²,

Dey³

et al. 2019

Egypt. J. Chem.

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T HE medical values of garlic, a traditionally used allium vegetable, were recognized as early as 3000 BC. Allicin, one of the major organosulfur compounds present in garlic, is associated with a wide variety of benificial activities like anticancer, anti-inflammatory, antiarthritic, antimicrobial, anti-diabetic, cholesterol-lowering, the potential to lower cardiovascular disorders, ameliorating neuron functions, etc. In this article, we have reviewed biological activities of allicin and related organosulfur compounds since the year 2010, using various scientific websites like Pub med, Google Scholar, Science Direct etc. Our literature review has highlighted many organo sulphur components of garlic and their possible mechanisms in curing different diseases. The information provided in this review will provide strategies for efficient organosulfur-based treatments of several diseases in future. Further research efforts are needed for a clear understanding of the interconnection between these functional components and various chronic diseases.

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“…29,30 In our previous study, both AGE and FruArg exhibited a capability to modulate neuroinflammatory responses by suppressing nitric oxide (NO) production, in a concentration-dependent manner, in lipopolysaccharide-induced mouse BV-2 microglial cells without affecting the cell viability. 31 This result has thus created a pretext for further studies aiming to evaluate the potential of AGE and FruArg in targeting neuroinflammation in vivo.…”

Section: Introductionmentioning

confidence: 99%

Development of a Method and Validation for the Quantitation of FruArg in Mice Plasma and Brain Tissue Using UPLC–MS/MS

et al. 2016

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Aged garlic extract (AGE) is a popular nutritional supplement and is believed to promote health benefits by exhibiting antioxidant and anti-inflammatory activities and hypolipidemic and antiplatelet effects. We have previously identified N-α-(1-deoxy-d-fructos-1-yl)-l-arginine (FruArg) as a major contributor to the bioactivity of AGE in BV-2 microglial cells whereby it exerted a significant ability to attenuate lipopolysaccharide-induced neuroinflammatory responses and to regulate the Nrf2-mediated antioxidant response. Here, we report on a sensitive ultraperformance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) protocol that was validated for the quantitation of FruArg in mouse plasma and brain tissue samples. Solid-phase extraction was used to separate FruArg from proteins and phospholipids present in the biological fluids. Results indicated that FruArg was readily absorbed into the blood circulation of mice after intraperitoneal injections. FruArg was reliably detected in the subregions of the brain tissue postinjection, indicating that it penetrates the blood–brain barrier in subnanomolar concentrations that are sufficient for its biological activity.

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Proteomic Analysis of the Effects of Aged Garlic Extract and Its FruArg Component on Lipopolysaccharide-Induced Neuroinflammatory Response in Microglial Cells

Cited by 29 publications

References 53 publications

Bioactive components from garlic on brain resiliency against neuroinflammation and neurodegeneration (Review)

Bioactive components from garlic on brain resiliency against neuroinflammation and neurodegeneration (Review)

Bioactivities of Allicin and Related Organosulfur Compounds from Garlic: Overview of the Literature Since 2010

Development of a Method and Validation for the Quantitation of FruArg in Mice Plasma and Brain Tissue Using UPLC–MS/MS

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