Safety and efficacy of aged garlic extract in dogs: upregulation of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway and Nrf2-regulated phase II antioxidant enzymes

As innate immune effector cells in the central nervous system (CNS), microglia not only are essential for the normal development of nervous system but also act on different neurological diseases, including Alzheimer’s disease (AD), Huntington's disease (HD), and other neuroinflammatory diseases. Mogroside V (Mog), a natural plant active ingredient and isolated form of Momordica grosvenori, has been shown to possess anti-inflammatory action, but few studies were carried out to investigate the effects of Mog on neuroinflammation. This study aimed to investigate the role of Mog in lipopolysaccharide- (LPS-) induced neuroinflammation and neuronal damage, revealing the underlying mechanisms. Our data indicated that Mog significantly inhibited the LPS-induced production of proinflammatory factors, such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-18, IL-6, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and high mobility group box 1 (HMGB1) in BV-2 cells. We found that Mog also suppressed toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), the phosphorylation of mitogen-activated protein kinases (MAPKs), adenosine 5′-monophosphate- (AMP-) activated protein kinase (AMPK), nuclear factor kappa-B (NF-κB), and protein kinase B (AKT). Moreover, Mog also enhanced the expression of γ-glutamyl cysteine synthetase catalytic subunit (GCLC), modifier subunit (GCLM), heme oxygenase-1 (HO-1), and quinine oxidoreductase 1 (NQO1) proteins, mostly depending on the nuclear translation of nuclear factor erythroid-2 related factor 2 (Nrf2). In contrast, pretreatment with inhibitors of AKT can suppress the phosphorylation of AMPK, Nrf2, and its downstream proteins expression. In summary, Mog might play a protective role against LPS-induced neurotoxicity by inhibiting the TLR4-MyD88 and activation of AMPK/AKT-Nrf2 signaling pathway.

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Therapeutic Targeting of the NRF2 Signaling Pathway in Cancer

Molecules ◽

10.3390/molecules26051417 ◽

2021 ◽

Vol 26 (5) ◽

pp. 1417

Author(s):

Pelin Telkoparan-Akillilar ◽

Emiliano Panieri ◽

Dilek Cevik ◽

Sibel Suzen ◽

Luciano Saso

Keyword(s):

Signaling Pathway ◽

Defense Mechanisms ◽

Cancer Targeting ◽

Related Factor ◽

Nuclear Factor ◽

Drug Candidates ◽

Cellular Defense ◽

Incidence And Mortality ◽

Nrf2 Signaling Pathway ◽

The Subject

Cancer is one of the most fatal diseases with an increasing incidence and mortality all over the world. Thus, there is an urgent need for novel therapies targeting major cancer-related pathways. Nuclear factor-erythroid 2-related factor 2 (NRF2) and its major negative modulator Kelch-like ECH-associated protein 1 (KEAP1) are main players of the cellular defense mechanisms against internal and external cell stressors. However, NRF2/KEAP1 signaling pathway is dysregulated in various cancers, thus promoting tumor cell survival and metastasis. In the present review, we discuss the mechanisms of normal and deregulated NRF2 signaling pathway focusing on its cancer-related functions. We further explore activators and inhibitors of this pathway as cancer targeting drug candidates in order to provide an extensive background on the subject.

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Protective Effect of Aged Garlic Extract Against the Oxidative Stress Induced by Acute Ionizing Irradiation on Hepatic Antioxidant Enzymes in Rats

European Journal of Clinical and Biomedical Sciences ◽

10.11648/j.ejcbs.20160206.13 ◽

2016 ◽

Vol 2 (6) ◽

pp. 69 ◽

Cited By ~ 1

Author(s):

Kouam Foubi Brice Bertrand ◽

Chuisseu Djamen Dieudonné Pascal ◽

Dzeufiet Djomeni Paul Désiré ◽

Samba Ngano Odette ◽

Mouelle Sone ◽

...

Keyword(s):

Oxidative Stress ◽

Antioxidant Enzymes ◽

Protective Effect ◽

Garlic Extract ◽

Aged Garlic Extract ◽

Ionizing Irradiation ◽

Aged Garlic

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Corrigendum to “Protective effect of aged garlic extract against the oxidative stress induced by cisplatin on blood cells parameters and hepatic antioxidant enzymes in rats” [Toxicol. Rep. 1 (2014) 682–691]

Toxicology Reports ◽

10.1016/j.toxrep.2016.12.005 ◽

2020 ◽

Vol 7 ◽

pp. e1647

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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Kaempferol protects rats with severe acute pancreatitis through regulating NF-κB and Keap1–Nrf2 signaling pathway

Italian Journal of Food Science ◽

10.15586/ijfs.v33i3.2100 ◽

2021 ◽

Vol 33 (3) ◽

pp. 25-32

Author(s):

Jun Cai ◽

Suyan Yao ◽

Hao Wang ◽

Wei Rong

Keyword(s):

Acute Pancreatitis ◽

Signaling Pathway ◽

Severe Acute Pancreatitis ◽

Sodium Taurocholate ◽

Pancreatic Injury ◽

Related Factor ◽

Inflammatory Disorder ◽

Nuclear Factor ◽

Western Blot Assay ◽

Nrf2 Signaling Pathway

Kaempferol (KF) is an important natural anti-inflammatory flavonol. Acute pancreatitis (AP) is an inflammatory disorder, which in about 20% cases may develop into severe acute pancreatitis (SAP) with a high mortality rate. This research was to study the effects and mechanism of kaempferol on SAP. SAP was induced by sodium taurocholate. The level of cytokines was analyzed by enzyme-linked-immunosorbent serologic assay. The expression of nuclear factor kappa B (NF-κB) and Kelch-like ECH-associated protein 1–nuclear factor erythroid 2-related factor 2 (Keap1–Nrf2) proteins was analyzed by Western blot assay. Pathological changes in the pancreas were evaluated by hematoxylin and eosin staining. Kaempferol attenuated pancreatic injury in SAP rats, including reduction in inflammatory infiltration and necrosis. The level of serum amylase and lipase was also decreased in kaempferol-treated SAP rats. Kaempferol inhibited the expression of inflammatory mediators (nuclear factor-α, Interlukin-1β, and Interlukin-6), and alleviated the oxidative stress characterized by the decreased malondialdehyde (MDA) and increased superoxide dismutase (SOD) levels. Kaempferol decreased the expression of cleaved caspase 3 and anti-apoptotic protein Bcl-2, which indicated that kaempferol could inhibit apoptosis of pancreatic cells in SAP rats. Kaempferol treatment could decrease the expression of p-p65 and the amount of nuclear Nrf2 (Nu-Nrf2), which demonstrated that kaempferol inhibited the NF-κB activation and enhanced the Keap1–Nrf2 pathway. Our research indicated that kaempferol could attenuate the pancreatic injury of SAP by regulating NF-κB and Keap1–Nrf2 signaling pathway. Kaempferol could serve as a natural candidate for treating SAP.

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Clusterin Protects Against Cr(VI)-Induced Oxidative Stress-Associated Hepatotoxicity By Mediating The Akt-Keap1-Nrf2 Signaling Pathway

10.21203/rs.3.rs-665264/v1 ◽

2021 ◽

Author(s):

Yu Ma ◽

Siwen Li ◽

Sixuan Tang ◽

Shuzi Ye ◽

Ningjuan Liang ◽

...

Keyword(s):

Oxidative Stress ◽

Signaling Pathway ◽

Environmental Pollutant ◽

Heme Oxygenase 1 ◽

Related Factor ◽

Nuclear Factor ◽

Oxygen Species ◽

Intervention Measures ◽

Exposed Population ◽

Nrf2 Signaling Pathway

Abstract Hexavalent chromium [Cr(VI)] is a serious environmental pollutant and threatens human health. Although it has been confirmed that oxidative stress is the main mechanism of liver injury caused by Cr(VI) exposure, the related toxic target and effective intervention measures have not been found. Clusterin (CLU) is an acute phase response protein with cytoprotective and apoptosis delaying effects, and its expression has been confirmed to increase significantly after exposure to Cr(VI). In this study, we demonstrate that CLU acts on the Protein Kinase B (PKB/Akt)-Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor E2-related factor 2 (Nrf2) signaling pathway to release Nrf2 into the nucleus. This to initiates the expression of a downstream protein, heme oxygenase 1 (HO-1), thereby attenuating the ubiquitination ability of Keap1 with Nrf2. We also demonstrated that CLU can affect oxidative stress through the Akt/Nrf2 pathway, which reduces the production of reactive oxygen species (ROS) induced by Cr(VI) and protects against Cr(VI)-induced oxidative stress-associated hepatotoxicity. This study demonstrates a the mechanism of Cr(VI)-induced hepatotoxicity, and indicates that CLU as an intervention target of oxidative stress can provide valuable experimental basis for the prevention and treatment of occupational diseases in Cr(VI)-exposed population.

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Aged Garlic Extract Inhibits CD36 Expression and Foam Cell Formation in Human Macrophages

Planta Medica ◽

10.1055/s-2007-987237 ◽

2007 ◽

Vol 73 (09) ◽

Author(s):

N Ide ◽

N Morihara ◽

L Paptheodorou ◽

R Stirner ◽

N Weiss

Keyword(s):

Foam Cell ◽

Cell Formation ◽

Garlic Extract ◽

Foam Cell Formation ◽

Aged Garlic Extract ◽

Human Macrophages ◽

Cd36 Expression ◽

Aged Garlic

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Cytoprotective Potential of Aged Garlic Extract (AGE) and Its Active Constituent, S-allyl-l-cysteine, in Presence of Carvedilol during Isoproterenol-Induced Myocardial Disturbance and Metabolic Derangements in Rats

Molecules ◽

10.3390/molecules26113203 ◽

2021 ◽

Vol 26 (11) ◽

pp. 3203

Author(s):

Syed Mohammed Basheeruddin Asdaq ◽

Obulesu Challa ◽

Abdulhakeem S. Alamri ◽

Walaa F. Alsanie ◽

Majid Alhomrani ◽

...

Keyword(s):

Myocardial Dysfunction ◽

Combined Therapy ◽

Myocardial Damage ◽

Thiobarbituric Acid ◽

Significant Rise ◽

Garlic Extract ◽

High Dose ◽

Aged Garlic Extract ◽

Active Constituent ◽

Aged Garlic

This study was conducted to determine the potential interaction of aged garlic extract (AGE) with carvedilol (CAR), as well as to investigate the role of S-allyl-l-cysteine (SAC), an active constituent of AGE, in rats with isoproterenol (ISO)-induced myocardial dysfunction. At the end of three weeks of treatment with AGE (2 and 5 mL/kg) or SAC (13.1 and 32.76 mg/kg), either alone or along with CAR (10 mg/kg) in the respective groups of animals, ISO was administered subcutaneously to induce myocardial damage. Myocardial infarction (MI) diagnostic predictor enzymes, lactate dehydrogenase (LDH) and creatinine kinase (CK-MB), were measured in both serum and heart tissue homogenates (HTH). Superoxide dismutase (SOD), catalase, and thiobarbituric acid reactive species (TBARS) were estimated in HTH. When compared with other groups, the combined therapy of high doses of AGE and SAC given alone or together with CAR caused a significant decrease in serum LDH and CK-MB activities. Further, significant rise in the LDH and CK-MB activities in HTH was noticed in the combined groups of AGE and SAC with CAR. It was also observed that both doses of AGE and SAC significantly increased endogenous antioxidants in HTH. Furthermore, histopathological observations corroborated the biochemical findings. The cytoprotective potential of SAC and AGE were dose-dependent, and SAC was more potent than AGE. The protection offered by aged garlic may be attributed to SAC. Overall, the results indicated that a high dose of AGE and its constituent SAC, when combined with carvedilol, has a synergistic effect in preventing morphological and physiological changes in the myocardium during ISO-induced myocardial damage.

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