Telomere damage response and low-grade inflammation.

PMID: 

Adv Exp Med Biol. 2017 ;1024:213-224. PMID: 28921472

Abstract Title: 

Telomere Damage Response and Low-Grade Inflammation.

Abstract: 

Telomeres at the ends of chromosomes safeguard genome integrity and stability in human nucleated cells. However, telomere repeats shed off during cell proliferation and other stress responses. Our recent studies show that telomere attrition induces not only epithelial stem cell senescence but also low-grade inflammation in the lungs. The senescence-associated low-grade inflammation (SALI) is characteristic of alveolar stem cell replicative senescence, increased proinflammatory and anti-inflammatory cytokines, infiltrated immune cells, and spillover effects. To date, the mechanisms underlying SALI remain unclear. Investigations demonstrate that senescent epithelial stem cells with telomere erosion are not the source of secreted cytokines, containing no significant increase in expression of the genes coding for increased cytokines, suggesting an alternative senescence-associated secretory phenotype (A-SASP). Given that telomere loss results in significant alterations in the genomes and accumulations of the cleaved telomeric DNA in the cells and milieu externe, we conclude that telomere position effects (TPEs) on gene expression and damage-associated molecular patterns (DAMPs) in antigen presentation are involved in A-SASP and SALI in response to telomere damage in mammals.

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Aged garlic extract and S-allylcysteine increase the GLUT3 and GCLC expression levels in cerebral ischemia.

PMID: 

Adv Clin Exp Med. 2019 Dec ;28(12):1609-1614. PMID: 31851788

Abstract Title: 

Aged garlic extract and S-allylcysteine increase the GLUT3 and GCLC expression levels in cerebral ischemia.

Abstract: 

BACKGROUND: During cerebral ischemia, energy restoration through the regulation of glucose transporters and antioxidant defense mechanisms is essential to maintain cell viability. Antioxidant therapy has been considered effective to attenuate brain damage; moreover, the regulation of transcription factors that positively regulate the expression of glucose transporters is associated with this therapy. Recently, it has been reported that the use of antioxidants such as S-allylcysteine (SAC), a component of aged garlic extract (AGE), improves survival in experimental models of cerebral ischemia.OBJECTIVES: The aim of this study was to determine the effect of AGE and SAC on the level of mRNA expression of the main neuronal glucose transporter (GLUT3) and the glutamate cysteine ligase catalytic subunit (GCLC) in rats with transient focal cerebral ischemia.MATERIAL AND METHODS: Cerebral ischemia was induced in male Wistar rats by middle cerebral artery occlusion (MCAO) for 2 h. The animals were sacrificed after different reperfusion times (0-48 h). Animals injected with AGE (360 mg/kg, intraperitoneally (i.p.)) and SAC (300 mg/kg, i.p.) at the beginning of reperfusion were sacrificed after 2 h. The mRNA expression level was analyzed in the fronto-parietal cortex using quantitative polymerase chain reaction (qPCR).RESULTS: Two major increases in GLUT3 expression at 1 h and 24 h of reperfusion were found. Both treatments increased GLUT3 and GCLC mRNA levels in control and under ischemic/reperfusion injury animals.CONCLUSIONS: This data suggests that SAC and AGE might induce neuroprotection, while controlling reactive oxygen species (ROS) levels, as indicated by the increase in GCLC expression, and regulating the energy content of the cell by increasing glucose transport mediated by GLUT3.

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Phytochemicals of garlic: Promising candidates for cancer therapy.

PMID: 

Biomed Pharmacother. 2020 Mar ;123:109730. Epub 2019 Dec 23. PMID: 31877551

Abstract Title: 

Phytochemicals of garlic: Promising candidates for cancer therapy.

Abstract: 

Of the numerous health benefits of garlic, the anticancer effect is probably the most noticeable. Observations over the past years have shown that the consumption of garlic in the diet provides strong protection against cancer risk. Previous studies involving garlic phytochemicals have usually focused on the cancer chemopreventive properties, but there is little published evidence showing its therapeutic potential in cancer treatment. In view of the multitargeted carcinoma actions and lack of severe toxicity, some components of garlic are likely to play vital roles in the selective killing of cancer cells. However, the rational design of experimental studies and clinical trials are required to verify this concept. This paper discusses the promises and pitfalls of garlic for the treatment of cancer.

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These results suggest that garlic oil reverses cisplatin-induced hepatorenal damage.

PMID: 

Sci Total Environ. 2020 Mar 25 ;710:136338. Epub 2019 Dec 28. PMID: 31923684

Abstract Title: 

Impact of garlic (Allium sativum) oil on cisplatin-induced hepatorenal biochemical and histopathological alterations in rats.

Abstract: 

Cisplatin (cis-diamminedichloridoplatinum II [CDDP]) is a chemotherapeutic agent used for treating different cancers types. However, its usage is limited because it induces harmful toxicities in multiple organs, including nephrotoxicity and hepatotoxicity. Garlic oil (GO) has several pharmacological activities, including antioxidant activity. The aim of the study is to evaluate the protective and antioxidant effects of GO against CDDP-induced acute liver and kidney injuries in male rats. CDDP-treated rats showed increased serum ALT, AST, ALP, LDH, uric acid, urea, creatinine, and IL-6 levels. Moreover, CDDP-treated rats showed significantly increased MDA and NO levels and decreased GSH level and T.SOD and CAT activities in hepatic and renal tissues compared with control rats. GO administration, especially at a dose of 100 ml/kg, alleviated CDDP-induced adverse biochemical and histopathological alterations and restored them to their normal values. These results suggest that GO reverses CDDP-induced hepatorenal damage by exerting antioxidant and anti-inflammatory effects.

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Effect of garlic’s active constituents in inflammation, obesity and cardiovascular disease.

PMID: 

Curr Hypertens Rep. 2020 Jan 10 ;22(1):6. Epub 2020 Jan 10. PMID: 31925548

Abstract Title: 

Effect of Garlic's Active Constituents in Inflammation, Obesity and Cardiovascular Disease.

Abstract: 

PURPOSE OF REVIEW: Several studies have attributed garlic's beneficial properties to its high content of organosulfur compounds (OSCs). Here, we summarized recent studies published and some own findings regarding OSCs and its effects on cardiovascular disease, inflammation, and obesity.RECENT FINDING: The analysis of the multiple actions produced by OSCs suggests that many of its bioactivities interfere against inflammation, oxidative stress, obesogenic effects, and mitochondrial dysfunction. Accumulating evidence from in vitro, animal, and human studies reinforce the notion that OSCs modify signaling pathways that trigger chronic diseases, and to highlight, actions over these pathways are related to the treatment of disorders addressed in this review. Garlic's bioactive OSCs behave like a nutraceutical panacea because they cover a broad spectrum of applications with promising impact for the prevention and treatment of prevalent chronic pathologies associated with low-grade inflammation.

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Possible role of garlic oil in ameliorating renal injury after liver ischemia/reperfusion.

PMID: 

J Physiol Pharmacol. 2019 Oct ;70(5). Epub 2020 Jan 30. PMID: 32009629

Abstract Title: 

Possible role of garlic oil in ameliorating renal injury after liver ischemia/reperfusion in rats.

Abstract: 

Acute liver failure induces renal injury by triggering inflammation and oxidative stress. The heme oxygenase system has a preventive role against reperfusion injury, while garlic oil has antioxidants and anti-inflammatory effects. This study investigated the protective effects of garlic oil pretreatment on remote renal functions after liver ischemia/reperfusion (I/R), and clarifying gene expressions of heme oxygenase 1 (HO1), autophagy-related 7 (Atg7) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) in renal tissues. Thirty six adult female Wistar rats were randomly divided into control, garlic oil-supplemented, liver I/R, and garlic oil-pretreated liver I/R groups. Liver ischemia was performed in anesthetized rats for 45 min, followed by reperfusion for 24 hours in metabolic cages. Serum samples were used for determination of liver enzymes and creatinine levels and total antioxidant capacity (TAC). Urine samples were assayed for albumin, volume and creatinine concentration. Right liver lobe and right kidney specimens were used for determination of oxidative stress markers (colorimeterically). Also, gene expressions of HO1, Atg7 and PGC1α were investigated in right kidney specimens using real time PCR. Left kidney specimens were used for histopathological studies. Liver I/R group exhibited higher liver enzymes and creatinine levels in serum, prominent oxidative stress in both liver and renal tissues, albuminuria, lowered GFR deranged renal structure, and upregulated HO1, Atg7 and PGC1α gene expressions in renal tissues. Garlic oil-pretreated I/R group restricted such detrimental changes in renal functions and structure, though it caused further upregulation of the studied gene expression in renal tissue to alleviate the oxidative stress. It is concluded that garlic oil exerted reno-protective effected against remote organ damage induced by liver I/R injury, through enhancing HO1, Atg7 and PGC1α gene expressions.

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Aged garlic extract reduces low attenuation plaque in coronary arteries of patients with diabetes.

PMID: 

Exp Ther Med. 2020 Feb ;19(2):1457-1461. Epub 2019 Dec 27. PMID: 32010322

Abstract Title: 

Aged garlic extract reduces low attenuation plaque in coronary arteries of patients with diabetes: A randomized, double-blind, placebo-controlled study.

Abstract: 

Several previous studies have demonstrated that aged garlic extract (AGE) inhibits the progression of coronary artery calcification and non-calcified plaque (NCP) in the general population. However, its effects on plaque progression in patients with diabetes have not yet been investigated, at least to the best of our knowledge. This study investigated whether AGE reduces the coronary plaque volume measured by cardiac computed tomography angiography (CCTA) in patients with diabetes mellitus (DM). A total of 80 participants with DM with a median age of 57 years were prospectively assigned to consume 2,400 mg AGE/day (after completion, 37 participants) or placebo (after completion, 29 participants) orally. Both groups underwent CCTA at baseline and follow-up 365 days apart. In total, 66 participants completed the study. Coronary plaque volume, including total plaque (TP), dense calcium (DC), fibrous, fibro-fatty and low-attenuation plaque (LAP) volumes were measured based upon pre-defined intensity cut-off values using semi-automated software (QAngio CT). Changes in various plaque types were normalized to the total coronary artery length. The non-parametric Wilcoxon rank-sum test was performed to examine the differences in plaque formation between the 2 groups. No significant differences were found in the baseline characteristics between the AGE and placebo groups. Compared with the placebo group, the AGE group exhibited a statistically significant regression in normalized LAP [median and standard deviation (SD) -0.2 (18.8) vs. 2.5 (69.3), P=0.0415]. No differences were observed in TP, fibrous, or fibrofatty plaque volumes between the AGE and placebo group. On the whole, this study indicated that the %LAP change in the AGE group was significantly greater than that in the placebo group in patients with diabetes. However, further studies are warranted to evaluate whether AGE has the ability to stabilize vulnerable plaque and decrease adverse cardiovascular events.

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Mechanisms underlying the attenuation of chronic inflammatory diseases by aged garlic extract: Involvement of the activation of AMP-activated protein kinase.

PMID: 

Exp Ther Med. 2020 Feb ;19(2):1462-1467. Epub 2019 Dec 27. PMID: 32010323

Abstract Title: 

Mechanisms underlying the attenuation of chronic inflammatory diseases by aged garlic extract: Involvement of the activation of AMP-activated protein kinase.

Abstract: 

AMP-activated protein kinase (AMPK) is an ubiquitously expressed serine/threonine kinase and an important regulator of energy metabolism. The decreased activity of AMPK induced by low-grade chronic inflammation has been implicated in several diseases, including type 2 diabetes and atherosclerosis. However, the activation of AMPK by natural and synthetic products can ameliorate these diseases through the inhibition of inflammation. For example, aged garlic extract (AGE) has been shown to enhance the phosphorylation of Thr172 of theα-subunit of AMPK in several tissues of disease model animals. In addition, AGE has been reported to suppress the progression of atherosclerotic plaque formation in an animal model of atherosclerosis. Moreover, AGE has been found to decrease the level of plasma glycated albumin and to improve hyperglycemia in an animal model of type 2 diabetes. These inhibitory effects of AGE are induced by the suppression of the inflammatory response. In the present review, we discuss the mechanisms through which AGE activates AMPK, as well as the mechanisms through which the activation of AMPK by AGE modulates the inflammatory response in disease models.

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Aged garlic extract reduces left ventricular myocardial mass in patients with diabetes.

PMID: 

Exp Ther Med. 2020 Feb ;19(2):1468-1471. Epub 2019 Dec 27. PMID: 32010324

Abstract Title: 

Aged garlic extract reduces left ventricular myocardial mass in patients with diabetes: A prospective randomized controlled double-blind study.

Abstract: 

Increased left ventricular myocardial mass (LVM) is a well known prognostic marker of poor cardiac outcomes. Decreases in LVM have been shown to decrease the cardiovascular risk. Aged garlic extract (AGE) has been shown to have an overall favorable effect on cardiac health; however, to the best of our knowledge, no study to date has specifically examined its effects on left ventricular mass. This study investigated whether AGE can affect LVM measured by cardiac computed tomography angiography (CCTA) in patients with diabetes mellitus (DM). This is a double-blind, placebo controlled randomized trial. In total, 65 participants with DM with a mean age of 58 years were prospectively assigned to consume 2,400 mg AGE/day or the placebo orally. Both groups underwent CCTA at baseline and follow-up at 1 year apart. LVM was measured using automated software. The baseline characteristics did not differ between the AGE and placebo groups. There was a trend towards a significant reduction in LVM at follow-up as compared to baseline in the AGE group (119.30±34.77 vs. 121.0±34.70, P=0.059). No change was observed in LVM in the placebo group at 1-year follow-up as compared to baseline (124.6±37.33 vs. 124.6±35.13, P=0.9). On the whole, this study indicated that AGE may decrease or stabilize LVM. Further studies however, with a larger sample size andlonger follow-up times are required to evaluate the effects of AGE on hypertension and LVM.

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