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Article ; Online: Canonical and non-canonical mechanisms of Nrf2 activation.

Silva-Islas, Carlos Alfredo / Maldonado, Perla D

2018 Volume 134, Page(s) 92–99

Abstract: Nuclear Factor Erythroid 2-related factor 2 (Nrf2) is a transcription factor that regulates the expression of genes involved in the metabolism, immune response, cellular proliferation, and other processes; however, the attention has been focused on the ... ...

Abstract	Nuclear Factor Erythroid 2-related factor 2 (Nrf2) is a transcription factor that regulates the expression of genes involved in the metabolism, immune response, cellular proliferation, and other processes; however, the attention has been focused on the study of its ability to induce the expression of proteins involved in the antioxidant defense. Nrf2 is mainly regulated by Kelch-like ECH-associated protein 1 (Keap1), an adapter substrate of Cullin 3 (Cul3) ubiquitin E3 ligase complex. Keap1 represses Nrf2 activity in the cytoplasm by its sequestering, ubiquitination and proteosomal degradation. Nrf2 activation, through the canonical mechanism, is carried out by electrophilic compounds and oxidative stress where some cysteine residues in Keap1 are oxidized, resulting in a decrease in Nrf2 ubiquitination and an increase in its nuclear translocation and activation. In the nucleus, Nrf2 induces a variety of genes involved in the antioxidant defense. Recently a new mechanism of Nrf2 activation has been described, called the non-canonical pathway, where proteins such as p62, p21, dipeptidyl peptidase III (DPP3), wilms tumor gene on X chromosome (WTX) and others are able to disrupt the Nrf2-Keap1 complex, by direct interaction with Keap1 decreasing Nrf2 ubiquitination and increasing its nuclear translocation and activation. In this review, the regulatory mechanisms involved in both canonical and non-canonical Nrf2 activation are discussed.
MeSH term(s)	Active Transport, Cell Nucleus ; Animals ; Gene Expression Regulation ; Humans ; NF-E2-Related Factor 2/genetics ; NF-E2-Related Factor 2/metabolism ; Oxidation-Reduction ; Oxidative Stress ; Proteasome Endopeptidase Complex/metabolism ; Proteolysis ; Signal Transduction ; Ubiquitination
Chemical Substances	NF-E2-Related Factor 2 ; NFE2L2 protein, human ; Proteasome Endopeptidase Complex (EC 3.4.25.1)
Language	English
Publishing date	2018-06-18
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1003347-6
ISSN	1096-1186 ; 0031-6989 ; 1043-6618
ISSN (online)	1096-1186
ISSN	0031-6989 ; 1043-6618
DOI	10.1016/j.phrs.2018.06.013
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Zs.A 721: Show issues

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Article ; Online: Antinociceptive effect of garlic, garlic preparations and derivative compounds.

Hernández-Cruz, Estefani Yaquelin / Silva-Islas, Carlos Alfredo / Maldonado, Perla D / Pedraza-Chaverri, José / Carballo-Villalobos, Azucena Ibeth

European journal of pain (London, England)

2022 Volume 26, Issue 5, Page(s) 947–964

Abstract: Background and objective: The antinociceptive effects of garlic have shown promise in treating different chronic diseases in humans, such as knee osteoarthritis, rheumatoid arthritis and peripheral arterial occlusive disease stage II. The most common ... ...

Abstract	Background and objective: The antinociceptive effects of garlic have shown promise in treating different chronic diseases in humans, such as knee osteoarthritis, rheumatoid arthritis and peripheral arterial occlusive disease stage II. The most common garlic products are garlic powder (dried garlic), steam distilled garlic oils, garlic oil macerate and aged garlic extract. These commercial products contain organosulphur compounds (OSCs) that have been extensively evaluated in preclinical models and some clinical assays to treat different diseases against pain. In this review, we describe the importance of some bioactive compounds found in garlic and their role in treating pain. Materials & methods: A systematic search of the literature in Dimensions, PubMed, Scopus, and Web of Science was performed. Terms and preselected keywords relating to garlic, its derivatives and organusulphure compounds in acute, chronic and neuropathic pain, were used to perform a systematic literature search. Two independent reviewers screened the papers for inclusion and assessed the methodological quality. Results & discussion: The antinociceptive activity of garlic and its OSC is related to its antioxidant and anti-inflammatory properties, which may be explained by the ability to block the synthesis of PGs, pro-inflammatory cytokines and interferon-γ, by the reduction COX-2 activity and increasing the levels of anti-inflammatory cytokines. Besides, garlic extract is an activator of TRPA1 and TRPV1, where the principal responsible for this activation are OSC. Conclusion: The relationship between these pathways allows a better understanding how garlic and its derivates could be carrying out its pharmacological action over the management of acute and chronic pain and provide a base by further investigations. Significance: Antinociceptive effect of garlic and its OSCs has been extensively evaluated in preclinical models and clinical assays to treat different diseases, contributing to the modulation of inflammation as an essential factor in reducing pain. The current review emphasizes the potential therapeutic effect of garlic and its derivatives in treatment of pain and related mechanisms of action. Moreover, it provides information about the potential clinical use in patients with painful conditions.
MeSH term(s)	Aged ; Analgesics/pharmacology ; Analgesics/therapeutic use ; Anti-Inflammatory Agents/pharmacology ; Anti-Inflammatory Agents/therapeutic use ; Antioxidants/pharmacology ; Cytokines ; Garlic ; Humans ; Neuralgia/drug therapy ; Plant Extracts/pharmacology ; Plant Extracts/therapeutic use ; Sulfur Compounds/pharmacology
Chemical Substances	Analgesics ; Anti-Inflammatory Agents ; Antioxidants ; Cytokines ; Plant Extracts ; Sulfur Compounds
Language	English
Publishing date	2022-03-22
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	1390424-3
ISSN	1532-2149 ; 1090-3801
ISSN (online)	1532-2149
ISSN	1090-3801
DOI	10.1002/ejp.1935
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Article: Antioxidant and Anti-Inflammatory Effects of Garlic in Ischemic Stroke: Proposal of a New Mechanism of Protection through Regulation of Neuroplasticity.

Bautista-Perez, Sandra Monserrat / Silva-Islas, Carlos Alfredo / Sandoval-Marquez, Oscar Uriel / Toledo-Toledo, Jesús / Bello-Martínez, José Manuel / Barrera-Oviedo, Diana / Maldonado, Perla D

Antioxidants (Basel, Switzerland)

2023 Volume 12, Issue 12

Abstract: Stroke represents one of the main causes of death and disability in the world; despite this, pharmacological therapies against stroke remain insufficient. Ischemic stroke is the leading etiology of stroke. Different molecular mechanisms, such as ... ...

Abstract	Stroke represents one of the main causes of death and disability in the world; despite this, pharmacological therapies against stroke remain insufficient. Ischemic stroke is the leading etiology of stroke. Different molecular mechanisms, such as excitotoxicity, oxidative stress, and inflammation, participate in cell death and tissue damage. At a preclinical level, different garlic compounds have been evaluated against these mechanisms. Additionally, there is evidence supporting the participation of garlic compounds in other mechanisms that contribute to brain tissue recovery, such as neuroplasticity. After ischemia, neuroplasticity is activated to recover cognitive and motor function. Some garlic-derived compounds and preparations have shown the ability to promote neuroplasticity under physiological conditions and, more importantly, in cerebral damage models. This work describes damage/repair mechanisms and the importance of garlic as a source of antioxidant and anti-inflammatory agents against damage. Moreover, we examine the less-explored neurotrophic properties of garlic, culminating in proposals and observations based on our review of the available information. The aim of the present study is to propose that garlic compounds and preparations could contribute to the treatment of ischemic stroke through their neurotrophic effects.
Language	English
Publishing date	2023-12-16
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2704216-9
ISSN	2076-3921
ISSN	2076-3921
DOI	10.3390/antiox12122126
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Article ; Online: Effect of Curcumin in Experimental Pulmonary Tuberculosis: Antimycobacterial Activity in the Lungs and Anti-Inflammatory Effect in the Brain.

Lara-Espinosa, Jacqueline V / Arce-Aceves, María Fernanda / López-Torres, Manuel O / Lozano-Ordaz, Vasti / Mata-Espinosa, Dulce / Barrios-Payán, Jorge / Silva-Islas, Carlos Alfredo / Maldonado, Perla D / Marquina-Castillo, Brenda / Hernández-Pando, Rogelio

International journal of molecular sciences

2022 Volume 23, Issue 4

Abstract: Tuberculosis (TB) is one of the ten leading causes of death worldwide. Patients with TB have been observed to suffer from depression and anxiety linked to social variables. Previous experiments found that the substantial pulmonary inflammation associated ...

Abstract	Tuberculosis (TB) is one of the ten leading causes of death worldwide. Patients with TB have been observed to suffer from depression and anxiety linked to social variables. Previous experiments found that the substantial pulmonary inflammation associated with TB causes neuroinflammation, neuronal death, and behavioral impairments in the absence of brain infection. Curcumin (CUR) is a natural product with antioxidant, anti-inflammatory and antibacterial activities. In this work, we evaluated the CUR effect on the growth control of mycobacteria in the lungs and the anti-inflammatory effect in the brain using a model of progressive pulmonary TB in BALB/c mice infected with drug-sensitive mycobacteria (strain H37Rv). The results have shown that CUR decreased lung bacilli load and pneumonia of infected animals. Finally, CUR significantly decreased neuroinflammation (expression of TNFα, IFNγ and IL12) and slightly increased the levels of nuclear factor erythroid 2-related to factor 2 (Nrf2) and the brain-derived neurotrophic factor (BDNF) levels, improving behavioral status. These results suggest that CUR has a bactericidal effect and can control pulmonary mycobacterial infection and reduce neuroinflammation. It seems that CUR has a promising potential as adjuvant therapy in TB treatment.
MeSH term(s)	Animals ; Anti-Inflammatory Agents/pharmacology ; Antitubercular Agents/pharmacology ; Brain/metabolism ; Brain/microbiology ; Brain-Derived Neurotrophic Factor/metabolism ; Curcumin/pharmacology ; Disease Models, Animal ; Inflammation/drug therapy ; Inflammation/metabolism ; Lung/metabolism ; Lung/microbiology ; Male ; Mice ; Mice, Inbred BALB C ; Mycobacterium tuberculosis/drug effects ; Tuberculosis/drug therapy ; Tuberculosis/metabolism ; Tuberculosis, Pulmonary/drug therapy ; Tuberculosis, Pulmonary/metabolism
Chemical Substances	Anti-Inflammatory Agents ; Antitubercular Agents ; Brain-Derived Neurotrophic Factor ; Curcumin (IT942ZTH98)
Language	English
Publishing date	2022-02-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23041964
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Article ; Online: Quinolinic Acid Induces Alterations in Neuronal Subcellular Compartments, Blocks Autophagy Flux and Activates Necroptosis and Apoptosis in Rat Striatum.

Silva-Islas, Carlos Alfredo / Santana-Martínez, Ricardo Alberto / León-Contreras, Juan Carlos / Barrera-Oviedo, Diana / Pedraza-Chaverri, Jose / Hernández-Pando, Rogelio / Maldonado, Perla D

Molecular neurobiology

2022 Volume 59, Issue 11, Page(s) 6632–6651

Abstract: Quinolinic acid (QUIN) is an agonist of N-methyl-D-aspartate receptor (NMDAr) used to study the underlying mechanism of excitotoxicity in animal models. There is evidence indicating that impairment in autophagy at early times contributes to cellular ... ...

Abstract	Quinolinic acid (QUIN) is an agonist of N-methyl-D-aspartate receptor (NMDAr) used to study the underlying mechanism of excitotoxicity in animal models. There is evidence indicating that impairment in autophagy at early times contributes to cellular damage in excitotoxicity; however, the status of autophagy in QUIN model on day 7 remains unexplored. In this study, the ultrastructural analysis of subcellular compartments and the status of autophagy, necroptosis, and apoptosis in the striatum of rats administered with QUIN (120 nmol and 240 nmol) was performed on day 7. QUIN induced circling behavior, neurodegeneration, and cellular damage; also, it promoted swollen mitochondrial crests, spherical-like morphology, and mitochondrial fragmentation; decreased ribosomal density in the rough endoplasmic reticulum; and altered the continuity of myelin sheaths in axons with separation of the compact lamellae. Furthermore, QUIN induced an increase and a decrease in ULK1 and p-70-S6K phosphorylation, respectively, suggesting autophagy activation; however, the increased microtubule-associated protein 1A/1B-light chain 3-II (LC3-II) and sequestosome-1/p62 (SQSTM1/p62), the coexistence of p62 and LC3 in the same structures, and the decrease in Beclin 1 and mature cathepsin D also indicates a blockage in autophagy flux. Additionally, QUIN administration increased tumor necrosis factor alpha (TNFα) and receptor-interacting protein kinase 3 (RIPK3) levels and its phosphorylation (p-RIPK3), as well as decreased B-cell lymphoma 2 (Bcl-2) and increased Bcl-2-associated X protein (Bax) levels and c-Jun N-terminal kinase (JNK) phosphorylation, suggesting an activation of necroptosis and apoptosis, respectively. These results suggest that QUIN activates the autophagy, but on day 7, it is blocked and organelle and cellular damage, neurodegeneration, and behavior alterations could be caused by necroptosis and apoptosis activation.
MeSH term(s)	Animals ; Apoptosis/physiology ; Autophagy/physiology ; Beclin-1/metabolism ; Cathepsin D/metabolism ; JNK Mitogen-Activated Protein Kinases/metabolism ; Lysosomes/metabolism ; Microtubule-Associated Proteins/metabolism ; Necroptosis ; Quinolinic Acid/toxicity ; Rats ; Receptors, N-Methyl-D-Aspartate/metabolism ; Sequestosome-1 Protein/metabolism ; Tumor Necrosis Factor-alpha/metabolism ; bcl-2-Associated X Protein/metabolism
Chemical Substances	Beclin-1 ; Microtubule-Associated Proteins ; Receptors, N-Methyl-D-Aspartate ; Sequestosome-1 Protein ; Tumor Necrosis Factor-alpha ; bcl-2-Associated X Protein ; JNK Mitogen-Activated Protein Kinases (EC 2.7.11.24) ; Cathepsin D (EC 3.4.23.5) ; Quinolinic Acid (F6F0HK1URN)
Language	English
Publishing date	2022-08-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	645020-9
ISSN	1559-1182 ; 0893-7648
ISSN (online)	1559-1182
ISSN	0893-7648
DOI	10.1007/s12035-022-02986-1
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Zs.A 2411: Show issues

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Article: Antitumor Effects of Natural Compounds Derived from Allium sativum on Neuroblastoma: An Overview

Patiño-Morales, Carlos César / Jaime-Cruz, Ricardo / Sánchez-Gómez, Concepción / Corona, Juan Carlos / Hernández-Cruz, Estefani Yaquelin / Kalinova-Jelezova, Ivia / Pedraza-Chaverri, José / Maldonado, Perla D. / Silva-Islas, Carlos Alfredo / Salazar-García, Marcela

Antioxidants. 2021 Dec. 27, v. 11, no. 1

2021

Abstract: Garlic (Allium sativum) has been used in alternative medicine to treat several diseases, such as cardiovascular and neurodegenerative diseases, cancer, and hepatic diseases. Several publications have highlighted other features of garlic, including its ... ...

Abstract	Garlic (Allium sativum) has been used in alternative medicine to treat several diseases, such as cardiovascular and neurodegenerative diseases, cancer, and hepatic diseases. Several publications have highlighted other features of garlic, including its antibacterial, antioxidative, antihypertensive, and antithrombotic properties. The properties of garlic result from the combination of natural compounds that act synergistically and cause different effects. Some garlic-derived compounds have been studied for the treatment of several types of cancer; however, reports on the effects of garlic on neuroblastoma are scarce. Neuroblastoma is a prevalent childhood tumor for which the search for therapeutic alternatives to improve treatment without affecting the patients’ quality of life continues. Garlic-derived compounds hold potential for the treatment of this type of cancer. A review of articles published to date on some garlic compounds and their effect on neuroblastoma was undertaken to comprehend the possible therapeutic role of these compounds. This review aimed to analyze the impact of some garlic compounds on cells derived from neuroblastoma.
Keywords	Allium sativum ; alternative medicine ; childhood ; garlic ; neoplasms ; quality of life
Language	English
Dates of publication	2021-1227
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2704216-9
ISSN	2076-3921
ISSN	2076-3921
DOI	10.3390/antiox11010048
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Acute expression of the transcription factor Nrf2 after treatment with quinolinic acid is not induced by oxidative stress in the rat striatum.

Silva-Islas, Carlos Alfredo / Chánez-Cárdenas, María Elena / Barrera-Oviedo, Diana / Ibarra-Rubio, María Elena / Maldonado, Perla D

Neurotoxicology

2019 Volume 73, Page(s) 120–131

Abstract: Quinolinic acid (QUIN) is an excitotoxic and pro-oxidant molecule used in the study of neurodegenerative disorders because it reproduces certain biochemical characteristics present in these diseases. The use of antioxidant molecules in the QUIN model ... ...

Abstract	Quinolinic acid (QUIN) is an excitotoxic and pro-oxidant molecule used in the study of neurodegenerative disorders because it reproduces certain biochemical characteristics present in these diseases. The use of antioxidant molecules in the QUIN model reduces cellular damage through the nuclear factor erythroid 2-related to factor 2 (Nrf2) pathway. The Nrf2 transcription factor is considered the master regulator of antioxidant genes expression, and its activation occurs by an increase in the reactive oxygen species (ROS) levels or in the presence of electrophilic compounds. However, Nrf2 activation also occurs in an oxidative stress-independent process caused by the disruption of the Keap1-Nrf2 complex by the direct interaction of Keap1 with certain proteins, such as DPP3 and p62. The aim of this study was to evaluate the effect of QUIN on Nrf2 activation over short periods of time. QUIN administration increased Nrf2 activation at 30 min in the striatum without increasing ROS production or modifying the redox cellular state. Moreover, QUIN increased Keap1 and Nrf2 nuclear levels and increased the protein-protein interaction between Keap1 and DPP3 and Keap1 and p62 30 min after QUIN administration. Finally, we found that Nrf2 activation primarily occurs in striatal neurons. Our results show that QUIN administration in vivo stimulates Nrf2 expression and activation in the absence of oxidative stress primarily in neurons and increases the interaction of p62 and DPP3 with Keap1, which could participate in Nrf2 activation.
MeSH term(s)	Animals ; Corpus Striatum/drug effects ; Corpus Striatum/metabolism ; Corpus Striatum/pathology ; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/metabolism ; Kelch-Like ECH-Associated Protein 1/metabolism ; Male ; NF-E2-Related Factor 2/genetics ; NF-E2-Related Factor 2/metabolism ; Neurons/drug effects ; Neurons/metabolism ; Neurons/pathology ; Oxidants/toxicity ; Oxidative Stress/drug effects ; Protein Binding ; Quinolinic Acid/toxicity ; Rats, Wistar ; Sequestosome-1 Protein/metabolism ; Time Factors ; Up-Regulation
Chemical Substances	KEAP1 protein, rat ; Kelch-Like ECH-Associated Protein 1 ; NF-E2-Related Factor 2 ; Nfe2l2 protein, rat ; Oxidants ; Sequestosome-1 Protein ; Sqstm1 protein, rat ; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases (EC 3.4.14.-) ; Quinolinic Acid (F6F0HK1URN)
Language	English
Publishing date	2019-03-12
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	800820-6
ISSN	1872-9711 ; 0161-813X
ISSN (online)	1872-9711
ISSN	0161-813X
DOI	10.1016/j.neuro.2019.03.003
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Article: Antitumor Effects of Natural Compounds Derived from

Patiño-Morales, Carlos César / Jaime-Cruz, Ricardo / Sánchez-Gómez, Concepción / Corona, Juan Carlos / Hernández-Cruz, Estefani Yaquelin / Kalinova-Jelezova, Ivia / Pedraza-Chaverri, José / Maldonado, Perla D / Silva-Islas, Carlos Alfredo / Salazar-García, Marcela

Antioxidants (Basel, Switzerland)

2021 Volume 11, Issue 1

Abstract: Garlic ( ...

Abstract	Garlic (
Language	English
Publishing date	2021-12-27
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2704216-9
ISSN	2076-3921
ISSN	2076-3921
DOI	10.3390/antiox11010048
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