Aged garlic extract suppresses the increase of plasma glycated albumin level and enhances the AMP‐activated protein kinase in adipose tissue in TSOD mice

Miki, Satomi; Inokuma, Ken-ichi; Takashima, Misako; Nishida, Morie; Sasaki, Yoko; Ushijima, Mitsuyasu; Suzuki, Junichiro; Morihara, Naoaki

doi:10.1002/mnfr.201600797

Cited by 31 publications

(34 citation statements)

References 31 publications

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“…Basic experiments have also studied the possible mechanisms of how allium vegetables improve metabolic, cardiovascular, and inflammatory outcomes. Animal studies confirmed that aged garlic extract could suppress the increase in plasma glycated albumin levels in spontaneous type 2 diabetes mouse models, and this effect might be partly explained by the activation of AMP‐activated protein kinase followed by the suppression of free fatty acid production and MCP1 gene expression in adipose tissue (Miki et al, ). In Sprague‐Dawley rats fed a high‐fat diet, oral administration of garlic and onion oil suppressed the high‐fat diet‐induced body weight gain, decreased the serum levels of TGs, TC, and LDL, and increased the level of HDL (Yang et al, ).…”

Section: Discussionmentioning

confidence: 91%

Allium vegetable consumption and health: An umbrella review of meta‐analyses of multiple health outcomes

Wan

Li³

et al. 2019

Food Science & Nutrition

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Previously, our meta‐analysis and other studies have suggested that allium vegetable consumption is beneficial for health, but no umbrella review has been conducted to assess the evidence of the various health benefits of allium vegetable consumption. Therefore, we conducted this umbrella review on this topic. This umbrella review included a total of 16 meta‐analyses with 50 unique outcomes. The most beneficial cancer‐related outcome was shown for gastric cancer (risk ratio 0.78; 95% confidence interval [CI] 0.67–0.91). In addition, only 8 weeks of garlic consumption significantly decreased serum total cholesterol (weighted mean differences −17.20 mg/dl; 95% CI −23.10 to −11.30), and patients with dyslipidemia who consumed garlic experienced more benefits than the whole population. Diabetic patients with longer durations of garlic intake experienced more benefits in terms of fasting blood glucose (FBG), HbA1c, and serum fructosamine than healthy participants, and garlic intake was associated with blood pressure reduction in hypertensive patients but not in normotensive participants. Limited side effects of garlic, such as garlic odor and gastrointestinal complaints, were reported among the included meta‐analyses. Our results suggested that allium vegetables might be beneficial for cancer prevention. In particular, garlic was comparatively safe and is recommended as a long‐term dietary component for patients with dyslipidemia, diabetes, and hypertension.

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Section: Discussionmentioning

confidence: 91%

Allium vegetable consumption and health: An umbrella review of meta‐analyses of multiple health outcomes

Wan

Li³

et al. 2019

Food Science & Nutrition

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“…These ndings suggested that anti-atherosclerotic effect of AGE may be attributable to its ability to protect and maintain the vascular endothelial barrier function. AGE has been reported to exert various pharmacological effects, such as anti-atherosclerotic [20,[22][23][24], anti-hypertensive [25,26] and anti-in ammatory effects [20,21], which are considered to be attributable to its sulfur-containing constituents. Therefore, we investigated whether S1PC, SAC and SAMC, three major sulfur-containing constituents in AGE, affect the endothelial barrier function.…”

Section: Discussionmentioning

confidence: 99%

“…Aged garlic extract (AGE) is a unique garlic preparation that is produced by aging of raw garlic in an aqueous ethanol solution for more than 10 months. AGE has been shown to exert various biological and pharmacological activities such as anti-in ammatory [20,21], anti-atherosclerotic [20,[22][23][24], antihypertensive [25,26] and anti-oxidative effects [27,28]. In particular, AGE prevented progression of cardiovascular diseases through the improvement of vascular endothelial dysfunction in clinical studies [24,26,[29][30][31][32].…”

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confidence: 99%

S-1-Propenylcysteine Improves TNF-α-Induced Vascular Endothelial Barrier Dysfunction by Suppressing the GEF-H1/RhoA/Rac Pathway

Kunimura

Miki

Takashima

et al. 2020

Preprint

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Background: Vascular endothelial barrier function is maintained by cell-to-cell junctional proteins and contributes to vascular homeostasis. Various risk factors such as inflammation disrupt barrier function through down-regulation of these proteins and promote vascular diseases such as atherosclerosis. Previous studies have demonstrated that aged garlic extract (AGE) and its sulfur-containing constituents exert the protective effects against several vascular diseases such as atherosclerosis. In this study, we examined whether AGE and its sulfur-containing constituents improve the endothelial barrier dysfunction elicited by a pro-inflammatory cytokine, Tumor-necrosis factor-α (TNF-α), and explored their mode of action on TNF-α signaling pathway.Methods: Human umbilical vein endothelial cells (HUVECs) were treated with test substances in the presence of TNF-α for various time periods. The endothelial permeability was measured by using a transwell permeability assay. The localization of cell-to-cell junctional proteins and actin cytoskeletons were visualized by immunostaining. RhoA and Rac activities were assessed by using GTP-binding protein pulldown assay. Gene and protein expression levels of signaling molecules were analyzed by real-time PCR and western blotting, respectively. Results: We found that AGE and its major sulfur-containing constituent, S-1-propenylcysteine (S1PC), reduced hyperpermeability elicited by TNF-α in HUVECs. In addition, S1PC inhibited TNF-α-induced production of myosin light chain (MLC) kinase and inactivation of MLC phosphatase through the suppression of the Rac and RhoA signaling pathways, respectively, which resulted in the dephosphorylation of MLC2, a key factor of actin remodeling. Moreover, S1PC inhibited the phosphorylation and activation of guanine nucleotide exchange factor-H1 (GEF-H1), a common upstream key molecule and activator of Rac and RhoA. These effects of S1PC were accompanied by its ability to protect the disruption of junctional proteins on the cell-cell contact regions and the increase of actin stress fibers induced by TNF-α. Conclusions: The present study suggested that AGE and S1PC improve endothelial barrier disruption through the protection of junctional proteins on plasma membrane.

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“…Aged garlic extract (AGE) is produced by extracting and aging garlic slices in an aqueous ethanol solution for >10 months and has been shown to modulate several immune functions, such as decreasing inflammatory cytokines and chemokines in animal models (1)(2)(3)(4). In addition, the supplementation of AGE was previously shown to increase the numbers of γδ-T and natural killer (NK) cells, and to reduce the levels of inflammatory cytokines, such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α, in a clinical study (5).…”

Section: Introductionmentioning

confidence: 99%

“…In addition, the supplementation of AGE was previously shown to increase the numbers of γδ-T and natural killer (NK) cells, and to reduce the levels of inflammatory cytokines, such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α, in a clinical study (5). AGE has been shown to exert immuno-enhancing and anti-inflammatory effects (1)(2)(3)(4)(5). S-1-propenylcysteine (S1PC), a major characteristic sulfur compound in AGE, which exhibits good oral bioavailability in rats and canines (6), has been shown to exert several beneficial effects, such as immunoregulatory, anti-hypertensive and blood flow-promoting effects (7)(8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

Regulation of immune response by S‑1‑propenylcysteine through autophagy‑mediated protein degradation (Review)

et al. 2019

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Autophagy is a key event in cellular recycling processes due to its involvement in the intracellular degradation of proteins. It has been demonstrated that S-1-propenylcysteine (S1PC), a characteristic sulfur compound in aged garlic extract, induces the activation of autophagy. S1PC degrades the adaptor protein myeloid differentiation response protein 88 (MyD88) of downstream of Toll-like receptor (TLR) by activating autophagy in vitro and in vivo. The degradation of MyD88 inhibits the TLR signaling pathway, including the phosphorylation of interleukin 1 receptor associated kinase 4 (IRAK4) and nuclear factor (NF)-κB p65 in vitro, and eventually leads to the inhibition of interleukin (IL)-6 production in vitro and CC motif chemokine ligand 2 (Ccl2) mRNA expression in vivo. S1PC also increases the level of intestinal immunoglobulin A (IgA) and the number of IgA-producing cells in Peyer's patches in vivo. In addition, S1PC triggers the mRNA expression of X-box binding protein 1 (Xbp1), an inducer of IgA-producing cell differentiation via the phosphorylation of extracellular signal-regulated kinase (ERK)1/2 and the degradation of paired box protein 5 (Pax5), a suppressor of Xbp1 mRNA expression. The present review summarizes the mechanisms through which the activation of autophagy by S1PC modulates the immune response. Contents 1. Introduction 2. S1PC induces the activation of autophagy 3. Anti-inflammatory effects of S1PC 4. Immuno-enhancing effects of S1PC 5. Conclusions and future perspectives Regulation of immune response by S-1-propenylcysteine through autophagy-mediated protein degradation (Review)

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Aged garlic extract suppresses the increase of plasma glycated albumin level and enhances the AMP‐activated protein kinase in adipose tissue in TSOD mice

Abstract: AGE treatment suppresses the increase of plasma glycated albumin level in TSOD mice and this effect is accompanied by the activation of AMPK in adipose tissue, and suggests that AGE may play a potential role in the prevention and treatment of type 2 diabetes.

Cited by 31 publications

References 31 publications

Allium vegetable consumption and health: An umbrella review of meta‐analyses of multiple health outcomes

Allium vegetable consumption and health: An umbrella review of meta‐analyses of multiple health outcomes

S-1-Propenylcysteine Improves TNF-α-Induced Vascular Endothelial Barrier Dysfunction by Suppressing the GEF-H1/RhoA/Rac Pathway

Regulation of immune response by S‑1‑propenylcysteine through autophagy‑mediated protein degradation (Review)

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