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Article ; Online: Reactogenic sleepiness after COVID-19 vaccination. A hypothesis involving orexinergic system linked to inflammatory signals.

Garrido-Suárez, Bárbara B / Garrido-Valdes, Mariana / Garrido, Gabino

2022 Volume 98, Page(s) 79–86

Abstract: Coronavirus disease 2019 (COVID-19) represents a global healthcare crisis that has led to morbidity and mortality on an unprecedented scale. While studies on COVID-19 vaccines are ongoing, the knowledge about the reactogenic symptoms that can occur after ...

Abstract	Coronavirus disease 2019 (COVID-19) represents a global healthcare crisis that has led to morbidity and mortality on an unprecedented scale. While studies on COVID-19 vaccines are ongoing, the knowledge about the reactogenic symptoms that can occur after vaccination and its generator mechanisms can be critical for healthcare professionals to improve compliance with the future vaccination campaign. Because sleep and immunity are bidirectionally linked, sleepiness or sleep disturbance side effects reported after some of the COVID-19 vaccines advise an academic research line in the context of physiological or pathological neuroimmune interactions. On the recognized basis of inflammatory regulation of hypothalamic neurons in sickness behavior, we hypothesized that IL-1β, INF-γ and TNF-α pro-inflammatory cytokines inhibit orexinergic neurons promoting sleepiness after peripheral activation of the innate immune system induced by the novel COVID-19 vaccines. In addition, based on knowledge of previous vaccines and disease manifestations of SARS-CoV-2 infection, it also suggests that narcolepsy must be included as potential adverse events of particular interest to consider in pharmacovigilance studies.
MeSH term(s)	COVID-19/prevention & control ; COVID-19 Vaccines/adverse effects ; Humans ; SARS-CoV-2 ; Sleepiness ; Vaccination/adverse effects
Chemical Substances	COVID-19 Vaccines
Language	English
Publishing date	2022-06-20
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2012041-2
ISSN	1878-5506 ; 1389-9457
ISSN (online)	1878-5506
ISSN	1389-9457
DOI	10.1016/j.sleep.2022.06.011
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Article ; Online: Antidiarrheal effect of Psidium guajava L. extract in acute diarrhea: a systematic review.

Garrido, Gabino / Garrido-Suárez, Bárbara B / Martínez-Tapia, Nicolás / Valdés-González, Marisela / Ortega-Mardones, Andrea

Journal of the science of food and agriculture

2024

Abstract: Acute diarrheal diseases are a leading cause of childhood mortality and morbidity worldwide. Psidium guajava has been globally used for its antidiarrheal potential. We conducted a systematic review of scientific articles published up to the year 2021, ... ...

Abstract	Acute diarrheal diseases are a leading cause of childhood mortality and morbidity worldwide. Psidium guajava has been globally used for its antidiarrheal potential. We conducted a systematic review of scientific articles published up to the year 2021, which included in vivo pre-clinical tests and clinical trials involving patients with acute infectious diarrhea to verify the antidiarrheal, antibacterial and antispasmodic effects of galenic preparations or phytopharmaceuticals from P. guajava. PRISMA and Rayyan were used as tools for the selection of studies collected in four databases (Pubmed, Scopus, Web of Science and Science Direct). The keywords used to carry out the search were: 'Psidium guajava', 'guava', 'antidiarrhe' and 'diarrhe', joined by Boolean operators 'OR' or 'AND'. The characteristics of studies in animal models of acute diarrhea induction, as well as in vivo and in vitro motility and microbiological tests linked with its main pathophysiological mechanisms, were collected. Twenty-three articles were included. Twenty (87%) of these reported heterogenic preclinical studies, predominating pharmacological studies of efficacy against conventional antidiarrheal agents, which utilized relevant outcomes and models of infectious diarrhea from the top pathogens in the clinic along with classical castor oil-induced diarrhea associated with motility tests. Only three articles (13%) corresponded to clinical trials investigating the efficacy, dose and safety of these preparations. Most studies reported positive results and significant mechanistic evidence from antibacterial, anti-motility, anti-secretory and protective/anti-inflammatory perspectives. However, further studies are needed to define the clinical significance and safety treatment with P. guajava extracts. © 2024 Society of Chemical Industry.
Language	English
Publishing date	2024-04-05
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	184116-6
ISSN	1097-0010 ; 0022-5142
ISSN (online)	1097-0010
ISSN	0022-5142
DOI	10.1002/jsfa.13515
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Article ; Online: Systematic review on the anxiolytic and hypnotic effects of flower extracts in in vivo pre-clinical studies published from 2010 to 2020.

Meneses, Constanza / Valdes-Gonzalez, Marisela / Garrido-Suárez, Barbara B / Garrido, Gabino

Phytotherapy research : PTR

2023 Volume 37, Issue 5, Page(s) 2144–2167

Abstract: Anxiety disorders are prevalent conditions in the world population, whose standard approaches include pharmacotherapy, psychotherapy, and combinations of these interventions. Different classes of psychopharmaceuticals are recommended as the first line of ...

Abstract	Anxiety disorders are prevalent conditions in the world population, whose standard approaches include pharmacotherapy, psychotherapy, and combinations of these interventions. Different classes of psychopharmaceuticals are recommended as the first line of drugs to treat these disorders, which can have several adverse effects, treatment resistance, dependence, and drug-drug interactions making it necessary to search for new therapeutic agents. In particular, diazepam (DZP), a prototype drug from the group of benzodiazepines, has been commonly used and evaluated for its efficacy and safety in different anxiety disorders in clinical trials. DZP is also the most widely used reference standard in in vivo pharmacological assays of natural compounds. However, translating the results obtained in different rodent species and physiological anxiety tests instead of psychopathological animal models that can be of clinical application remains challenging. A systematic review of scientific articles published between 2010 and 2020 that included in vivo pre-clinical tests to define the anxiolytic, sedative and/or hypnotic effect of flower extracts is proposed. PRISMA and Rayyan were used for the selection of studies using four databases (Pubmed, Scopus, Web of Science, and QInsight), using the keywords: "Animals," "Anxiolytic," "Diazepam," "Elevated Plus Maze," "Flower Extracts," "Insomnia," "In vivo," "Mice," "Open Field Test," "Pre clinical" and "Sedative." The characteristics of anxiety studies in animal models, other studies related to locomotor activity, and the hypnotic effect of the extracts were compiled. Twenty-four articles were included, 21 of them performed the animal model of anxiety-like behavior of the elevated plus maze, seven the open field test, and six the light-dark box test. The locomotor activity was evaluated in 10 studies after the administration of the extracts to the animals to define their sedative effect, where only one defined that the extract (Matricaria chamomilla) had a sedative effect. The plants declared with this type of activity were Achyranthes aspera, Alcea aucheri, Brassica nigra, Cananga odorata, Carthamus tinctorius, Chrysanthemum indicum, Citrus aurantium, Couroupita guianensis, Echium amoenum, Erythrina berteroana, Gardenia jasminoides, Hibiscus tilliaceus, Lavandula officinalis, Lawsonia inermis, Matricaria chamomilla, Melia azedarach, Nerium oleander, Passiflora incarnata, Plumeria rubra, Salix aegyptiaca, Syzygium aromaticum, Tagetes erecta, Tilia americana. Although this review showed that some flower extracts have an anxiolytic effect as effective as diazepam, their therapeutic utility in anxiety disorders remains to be extensively demonstrated. Hence, more reliable and predictive behavioral tests and appropriate strategies for the experimental designs are needed to obtain more conclusive evidence with clinical significance.
MeSH term(s)	Mice ; Animals ; Anti-Anxiety Agents/pharmacology ; Anti-Anxiety Agents/therapeutic use ; Hypnotics and Sedatives/pharmacology ; Research Design ; Plant Extracts/pharmacology ; Plant Extracts/therapeutic use ; Anxiety/drug therapy ; Diazepam/pharmacology ; Oils, Volatile/pharmacology ; Maze Learning ; Flowers ; Behavior, Animal
Chemical Substances	Anti-Anxiety Agents ; Hypnotics and Sedatives ; Plant Extracts ; Diazepam (Q3JTX2Q7TU) ; Oils, Volatile
Language	English
Publishing date	2023-04-11
Publishing country	England
Document type	Systematic Review ; Journal Article ; Review
ZDB-ID	639136-9
ISSN	1099-1573 ; 0951-418X
ISSN (online)	1099-1573
ISSN	0951-418X
DOI	10.1002/ptr.7830
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Article ; Online: Gastroprotective Role of Fruit Extracts in Gastric Damage Induced by Non-Steroidal Anti-Inflammatory Drugs: A Systematic Review.

Garrido-Valdes, Mariana / Díaz-Velis, Leonor / Valdes-Gonzalez, Marisela / Garrido-Suárez, Barbara B / Garrido, Gabino

Journal of medicinal food

2023 Volume 26, Issue 11, Page(s) 777–798

Abstract: The aim of this study was to systematically review the scientific literature, with Preferred Reporting Items of Systematic Reviews and Meta-analyses (PRISMA) guidelines, of the articles found in the past 11 years on the gastroprotective role of fruit ... ...

Abstract	The aim of this study was to systematically review the scientific literature, with Preferred Reporting Items of Systematic Reviews and Meta-analyses (PRISMA) guidelines, of the articles found in the past 11 years on the gastroprotective role of fruit extracts in gastric ulcers induced by non-steroidal anti-inflammatory drugs (NSAIDs). Scientific articles published between 2010 and 2020 were included in this systematic review, including
MeSH term(s)	Rats ; Animals ; Stomach Ulcer/chemically induced ; Stomach Ulcer/drug therapy ; Stomach Ulcer/metabolism ; Antioxidants/metabolism ; Fruit/metabolism ; Gastric Mucosa/metabolism ; Plant Extracts/therapeutic use ; Rats, Wistar ; Anti-Ulcer Agents/pharmacology ; Anti-Ulcer Agents/therapeutic use ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Indomethacin/adverse effects ; Aspirin/adverse effects ; Aspirin/metabolism
Chemical Substances	Antioxidants ; Plant Extracts ; Anti-Ulcer Agents ; Anti-Inflammatory Agents, Non-Steroidal ; Indomethacin (XXE1CET956) ; Aspirin (R16CO5Y76E)
Language	English
Publishing date	2023-10-30
Publishing country	United States
Document type	Systematic Review ; Journal Article ; Review
ZDB-ID	1427365-2
ISSN	1557-7600 ; 1096-620X
ISSN (online)	1557-7600
ISSN	1096-620X
DOI	10.1089/jmf.2023.0005
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Zs.A 5916: Show issues

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Article ; Online: Modified pectin with anticancer activity in breast cancer: A systematic review.

Garrido, Gabino / Garrido-Suárez, Bárbara B / Mieres-Arancibia, Mario / Valdes-Gonzalez, Marisela / Ardiles-Rivera, Alejandro

International journal of biological macromolecules

2023 Volume 254, Issue Pt 1, Page(s) 127692

Abstract: Breast cancer is the most commonly diagnosed cancer among women worldwide. The current pharmacological treatments for breast cancer have numerous adverse effects and are not always effective. Recently, the anticancer activity of modified pectins (MPs) ... ...

Abstract	Breast cancer is the most commonly diagnosed cancer among women worldwide. The current pharmacological treatments for breast cancer have numerous adverse effects and are not always effective. Recently, the anticancer activity of modified pectins (MPs) against various types of cancers, including breast cancer, has been investigated. This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) model, including scientific articles from the last 22 years that measured the anticancer activity of MPs on breast cancer. The articles were searched in four databases with the terms: "modified pectin" and "breast cancer". Nine articles were included, five in vitro and four mixed (in vitro and in vivo). Different models and methods by which anticancer activity was measured were analyzed. All the studies reported positive results in both cell lines and in vivo murine models of breast cancer. The extracted data suggest a positive effect and provide mechanistic evidence of MPs in the treatment of breast cancer. However, as limited number of studies were included, further in vivo studies are required to obtain more conclusive preclinical evidence.
MeSH term(s)	Humans ; Female ; Mice ; Animals ; Pectins/pharmacology ; Pectins/therapeutic use ; Breast Neoplasms/drug therapy
Chemical Substances	Pectins (89NA02M4RX)
Language	English
Publishing date	2023-10-26
Publishing country	Netherlands
Document type	Systematic Review ; Journal Article ; Review
ZDB-ID	282732-3
ISSN	1879-0003 ; 0141-8130
ISSN (online)	1879-0003
ISSN	0141-8130
DOI	10.1016/j.ijbiomac.2023.127692
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Article ; Online: Systematic review on the anxiolytic and hypnotic effects of flower extracts in in vivo pre‐clinical studies published from 2010 to 2020

Meneses, Constanza / Valdes‐Gonzalez, Marisela / Garrido‐Suárez, Barbara B. / Garrido, Gabino

Phytotherapy Research. 2023 May, v. 37, no. 5 p.2144-2167

2023

Abstract	Anxiety disorders are prevalent conditions in the world population, whose standard approaches include pharmacotherapy, psychotherapy, and combinations of these interventions. Different classes of psychopharmaceuticals are recommended as the first line of drugs to treat these disorders, which can have several adverse effects, treatment resistance, dependence, and drug–drug interactions making it necessary to search for new therapeutic agents. In particular, diazepam (DZP), a prototype drug from the group of benzodiazepines, has been commonly used and evaluated for its efficacy and safety in different anxiety disorders in clinical trials. DZP is also the most widely used reference standard in in vivo pharmacological assays of natural compounds. However, translating the results obtained in different rodent species and physiological anxiety tests instead of psychopathological animal models that can be of clinical application remains challenging. A systematic review of scientific articles published between 2010 and 2020 that included in vivo pre‐clinical tests to define the anxiolytic, sedative and/or hypnotic effect of flower extracts is proposed. PRISMA and Rayyan were used for the selection of studies using four databases (Pubmed, Scopus, Web of Science, and QInsight), using the keywords: “Animals,” “Anxiolytic,” “Diazepam,” “Elevated Plus Maze,” “Flower Extracts,” “Insomnia,” “In vivo,” “Mice,” “Open Field Test,” “Pre clinical” and “Sedative.” The characteristics of anxiety studies in animal models, other studies related to locomotor activity, and the hypnotic effect of the extracts were compiled. Twenty‐four articles were included, 21 of them performed the animal model of anxiety‐like behavior of the elevated plus maze, seven the open field test, and six the light–dark box test. The locomotor activity was evaluated in 10 studies after the administration of the extracts to the animals to define their sedative effect, where only one defined that the extract (Matricaria chamomilla) had a sedative effect. The plants declared with this type of activity were Achyranthes aspera, Alcea aucheri, Brassica nigra, Cananga odorata, Carthamus tinctorius, Chrysanthemum indicum, Citrus aurantium, Couroupita guianensis, Echium amoenum, Erythrina berteroana, Gardenia jasminoides, Hibiscus tilliaceus, Lavandula officinalis, Lawsonia inermis, Matricaria chamomilla, Melia azedarach, Nerium oleander, Passiflora incarnata, Plumeria rubra, Salix aegyptiaca, Syzygium aromaticum, Tagetes erecta, Tilia americana. Although this review showed that some flower extracts have an anxiolytic effect as effective as diazepam, their therapeutic utility in anxiety disorders remains to be extensively demonstrated. Hence, more reliable and predictive behavioral tests and appropriate strategies for the experimental designs are needed to obtain more conclusive evidence with clinical significance.
Keywords	Achyranthes aspera ; Alcea ; Brassica nigra ; Cananga odorata ; Carthamus tinctorius ; Chrysanthemum indicum ; Citrus aurantium ; Couroupita guianensis ; Echium amoenum ; Erythrina berteroana ; Gardenia jasminoides ; Hibiscus ; Lavandula angustifolia subsp. angustifolia ; Lawsonia inermis ; Matricaria chamomilla ; Melia azedarach ; Nerium oleander ; Passiflora incarnata ; Plumeria rubra ; Salix capensis ; Syzygium aromaticum ; Tagetes erecta ; Tilia americana ; animal models ; anxiety ; diazepam ; drug therapy ; elevated plus-maze test ; flowers ; locomotion ; phytotherapy ; prototypes ; psychotherapy ; reference standards ; rodents ; systematic review ; tranquilizers
Language	English
Dates of publication	2023-05
Size	p. 2144-2167.
Publishing place	John Wiley & Sons, Ltd.
Document type	Article ; Online
Note	REVIEW
ZDB-ID	639136-9
ISSN	1099-1573 ; 0951-418X
ISSN (online)	1099-1573
ISSN	0951-418X
DOI	10.1002/ptr.7830
Database	NAL-Catalogue (AGRICOLA)

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Article: Mangiferin: Possible uses in the prevention and treatment of mixed osteoarthritic pain

Garrido‐Suárez, Bárbara B / Garrido, Gabino / Piñeros, Octavio / Delgado‐Hernández, René

Phytotherapy research. 2020 Mar., v. 34, no. 3

2020

Abstract: Osteoarthritis (OA) pain has been proposed to be a mixed pain state, because in some patients, central nervous system factors are superimposed upon the more traditional peripheral factors. In addition, a considerable amount of preclinical and clinical ... ...

Abstract	Osteoarthritis (OA) pain has been proposed to be a mixed pain state, because in some patients, central nervous system factors are superimposed upon the more traditional peripheral factors. In addition, a considerable amount of preclinical and clinical evidence has shown that, accompanying the central neuroplasticity changes and partially driven by a peripheral nociceptive input, a real neuropathic component occurs that are particularly linked to disease severity and progression. Hence, innovative strategies targeting neuroprotection and particularly neuroinflammation to prevent and treat OA pain could be introduced. Mangiferin (MG) is a glucosylxanthone that is broadly distributed in higher plants, such as Mangifera indica L. Previous studies have documented its analgesic, anti‐inflammatory, antioxidant, neuroprotective, and immunomodulatory properties. In this paper, we propose its potential utility as a multitargeted compound for mixed OA pain, even in the context of multimodal pharmacotherapy. This hypothesis is supported by three main aspects: the cumulus of preclinical evidence around this xanthone, some preliminary clinical results using formulations containing MG in clinical musculoskeletal or neuropathic pain, and by speculations regarding its possible mechanism of action according to recent advances in OA pain knowledge.
Keywords	Mangifera indica ; analgesics ; antioxidants ; central nervous system ; disease severity ; drug therapy ; immunomodulators ; mechanism of action ; musculoskeletal system ; neuroplasticity ; neuroprotective effect ; osteoarthritis ; pain ; patients ; xanthone
Language	English
Dates of publication	2020-03
Size	p. 505-525.
Publishing place	John Wiley & Sons, Ltd
Document type	Article
Note	REVIEW
ZDB-ID	639136-9
ISSN	1099-1573 ; 0951-418X
ISSN (online)	1099-1573
ISSN	0951-418X
DOI	10.1002/ptr.6546
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Synergistic interaction between amitriptyline and paracetamol in persistent and neuropathic pain models: An isobolografic analysis.

Garrido-Suárez, Bárbara B / Garrido, Gabino / Bellma Menéndez, Addis / Merino, Nelson / Valdés, Odalys / Delgado-Hernández, René / Granados-Soto, Vinicio

Neurochemistry international

2021 Volume 150, Page(s) 105160

Abstract: The current study was designed to evaluate the transient antinociceptive interaction between amitriptyline and paracetamol in the formalin test. In addition, considering other long-term neuroprotective mechanisms of these drugs, we hypothesized that this ...

Abstract	The current study was designed to evaluate the transient antinociceptive interaction between amitriptyline and paracetamol in the formalin test. In addition, considering other long-term neuroprotective mechanisms of these drugs, we hypothesized that this combination might exert some synergistic effects on neuropathic pain linked with its possible ability to prevent Wallerian degeneration (WD). The effects of individual and fixed-ratio of 1:1 combinations of orally administered amitriptyline and paracetamol were assayed in the two phases of the formalin test and in the chronic constriction injury (CCI) model in rats. Isobolographic analysis was employed to characterize the synergism produced by the combinations. Amitriptyline, paracetamol, and fixed-ratio amitriptyline-paracetamol combinations produced dose-dependent antinociceptive effects mainly on the inflammatory tonic phase. Repeated doses of individual drugs and their combination decreased CCI-induced mechanical allodynia in a dose-dependent manner. ED
MeSH term(s)	Acetaminophen/administration & dosage ; Administration, Oral ; Amitriptyline/administration & dosage ; Analgesics, Non-Narcotic/administration & dosage ; Animals ; Dose-Response Relationship, Drug ; Drug Synergism ; Male ; Neuralgia/drug therapy ; Neuralgia/pathology ; Pain Measurement/drug effects ; Pain Measurement/methods ; Rats ; Rats, Sprague-Dawley
Chemical Substances	Analgesics, Non-Narcotic ; Amitriptyline (1806D8D52K) ; Acetaminophen (362O9ITL9D)
Language	English
Publishing date	2021-08-16
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	283190-9
ISSN	1872-9754 ; 0197-0186
ISSN (online)	1872-9754
ISSN	0197-0186
DOI	10.1016/j.neuint.2021.105160
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Article ; Online: Mangiferin: Possible uses in the prevention and treatment of mixed osteoarthritic pain.

Garrido-Suárez, Bárbara B / Garrido, Gabino / Piñeros, Octavio / Delgado-Hernández, René

Phytotherapy research : PTR

2019 Volume 34, Issue 3, Page(s) 505–525

Abstract	Osteoarthritis (OA) pain has been proposed to be a mixed pain state, because in some patients, central nervous system factors are superimposed upon the more traditional peripheral factors. In addition, a considerable amount of preclinical and clinical evidence has shown that, accompanying the central neuroplasticity changes and partially driven by a peripheral nociceptive input, a real neuropathic component occurs that are particularly linked to disease severity and progression. Hence, innovative strategies targeting neuroprotection and particularly neuroinflammation to prevent and treat OA pain could be introduced. Mangiferin (MG) is a glucosylxanthone that is broadly distributed in higher plants, such as Mangifera indica L. Previous studies have documented its analgesic, anti-inflammatory, antioxidant, neuroprotective, and immunomodulatory properties. In this paper, we propose its potential utility as a multitargeted compound for mixed OA pain, even in the context of multimodal pharmacotherapy. This hypothesis is supported by three main aspects: the cumulus of preclinical evidence around this xanthone, some preliminary clinical results using formulations containing MG in clinical musculoskeletal or neuropathic pain, and by speculations regarding its possible mechanism of action according to recent advances in OA pain knowledge.
MeSH term(s)	Analgesics/therapeutic use ; Humans ; Hyperalgesia/etiology ; Mangifera/chemistry ; Neuralgia/drug therapy ; Neuralgia/etiology ; Neuralgia/prevention & control ; Neuroprotection/drug effects ; Osteoarthritis/complications ; Xanthones/therapeutic use
Chemical Substances	Analgesics ; Xanthones ; mangiferin (1M84LD0UMD)
Language	English
Publishing date	2019-11-22
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	639136-9
ISSN	1099-1573 ; 0951-418X
ISSN (online)	1099-1573
ISSN	0951-418X
DOI	10.1002/ptr.6546
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Anti-hypernociceptive and anti-inflammatory effects of JM-20: A novel hybrid neuroprotective compound.

Garrido-Suárez, Bárbara B / Garrido, Gabino / Castro-Labrada, Marian / Merino, Nelson / Valdés, Odalys / Pardo, Zenia / Ochoa-Rodríguez, Estael / Verdecia-Reyes, Yamila / Delgado-Hernández, René / Godoy-Figueiredo, Jozi / Ferreira, Sergio H

Brain research bulletin

2020 Volume 165, Page(s) 185–197

Abstract: ... 2-methyl-4-(2-nitrophenyl)-411-dihydro-1H-pyrido[2,3-b] [1,5] benzodiazepine) on pain-related ...

Abstract	The present study examines the possible effect of the novel hybrid molecule JM-20 (3-ethoxycarbonyl-2-methyl-4-(2-nitrophenyl)-411-dihydro-1H-pyrido[2,3-b] [1,5] benzodiazepine) on pain-related behaviours in a persistent pain model (5% formalin test) and in the neutrophil migration events during the inflammatory process. It further introduces JM-20 in a chronic constriction injury (CCI) model to clarify the possible subjacent mechanisms with its consequent clinical relevance. A single administration of JM-20 (20 or 40 mg/kg, per os [p.o.]) decreased licking/biting exclusively in the tonic phase of the formalin test in a GABA/benzodiazepine (BZD) receptor antagonist flumazenil-sensitive manner. JM-20 reduced in vivo neutrophil migration, rolling and adhesion to the endothelium induced by intraperitoneal administration of carrageenan in mice. In addition, plasma extravasation and tumour necrosis factor alpha production in the peritoneal fluid were decreased. Treatment with JM-20 (20 mg/kg, p.o.) for 7 days after CCI reduced mechanical hypersensitivity in a NG-monomethyl-l-arginine (L-NMMA)/methylene blue/glibenclamide-sensitive manner. Histopathological signs of Wallerian degeneration (WD) of the sciatic nerve were also attenuated, as well as interleukin-1 beta release in the spinal cord. The nitrate/nitrite concentration was increased centrally and did not show differences at the peripheral nerve level. The findings of this study suggest JM-20 can decrease persistent pain. A transient activity of its BDZ portion on nociceptive pathways mediated by GABA/BDZ receptors in association with its anti-inflammatory properties could be at least partially involved in this effect. JM-20 decreased CCI-induced mechanical hypersensitivity via the l-arginine/nitric oxide (NO)/cyclic GMP-sensitive ATP-sensitive potassium channel pathway. Its neuroprotective ability by preventing WD could be implicated in its anti-neuropathic mechanisms.
MeSH term(s)	Animals ; Behavior, Animal/drug effects ; Benzodiazepines/pharmacology ; Benzodiazepines/therapeutic use ; Cell Movement/drug effects ; Inflammation/drug therapy ; Inflammation/pathology ; Male ; Neuroprotective Agents/pharmacology ; Neuroprotective Agents/therapeutic use ; Neutrophils/drug effects ; Niacin/analogs & derivatives ; Niacin/pharmacology ; Niacin/therapeutic use ; Pain/drug therapy ; Pain/pathology ; Pain Measurement ; Pain Threshold/drug effects ; Rats ; Rats, Sprague-Dawley ; Sciatic Nerve/drug effects ; Sciatic Nerve/pathology
Chemical Substances	3-ethoxycarbonyl-2-methyl-4-(2-nitrophenyl)-4,11-dihydro-1H-pyrido(2,3-b)(1,5)benzodiazepine ; Neuroprotective Agents ; Benzodiazepines (12794-10-4) ; Niacin (2679MF687A)
Language	English
Publishing date	2020-10-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	197620-5
ISSN	1873-2747 ; 0361-9230
ISSN (online)	1873-2747
ISSN	0361-9230
DOI	10.1016/j.brainresbull.2020.10.003
Database	MEDical Literature Analysis and Retrieval System OnLINE

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