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Zamora-Díaz IY, González-Trujano ME, Martínez-Vargas D, Moreno-Pérez GF, Hernandez-Leon A, Narváez-González HF, Ventura-Martínez R, Pellicer F, López-Muñoz FJ. Pharmacological interactions of sulforaphane and gabapentin in a murine fibromyalgia-like pain model. Biomed Pharmacother 2025; 184:117929. [PMID: 39970732 DOI: 10.1016/j.biopha.2025.117929] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Revised: 01/06/2025] [Accepted: 02/15/2025] [Indexed: 02/21/2025] Open
Abstract
Therapeutic management of a chronic painful syndrome such as fibromyalgia (FM) lacks effective and safe single or combined analgesics. Current medications such as gabapentin (GPB) or pregabalin are moderately effective but in the presence of several adverse effects. Natural products derived from cruciferous vegetables such as sulforaphane (SFN) produce neuroprotective effects due to their potent antioxidant and anti-inflammatory properties. However, it is unknown whether positive or negative pharmacological interactions may occur when GBP and SFN are combined. The aim of this study was to estimate the pharmacological interaction of GBP and SFN in FM-like pain induced in rats. Time course curves of antiallodynic and antihyperalgesic effects were constructed for both SFN (3.16, 31.6, and 100 mg/kg, i.p.) and GBP (10, 31.6, and 100 mg/kg, i.p.) by recording behavioral responses every 30 min and up to 4 h afterward, from which dose-response effects were also obtained to decide the dosage combination. An electrocorticographic (ECoG) recording in mice and docking analysis were also explored to explain the pharmacological interaction. Our results demonstrated significant and dose-dependent antiallodynic and antihyperalgesic effects in their individual administration. While a combination of intermediate doses of these drugs enhanced their effects producing the same level as that obtained by using only 1/3 of the individual dose in each case. The ECoG recording and docking analysis suggest that calcium channels could be partly involved in the drug interaction. This study provides preclinical evidence that SFN alone and in combination with GBP may be beneficial for relieving FM-like pain at certain doses.
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Affiliation(s)
- Ik-Yahalcab Zamora-Díaz
- Centro Médico Nacional 20 de Noviembre, Félix Cuevas 540, Col. Del Valle Sur, Benito Juárez, Ciudad de México 03104, Mexico.
| | - María Eva González-Trujano
- Laboratorio de Neurofarmacología de Productos Naturales, Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Calz. México-Xochimilco 101, Col. San Lorenzo Huipulco, Tlalpan, Ciudad de México 14370, Mexico.
| | - David Martínez-Vargas
- Laboratorio de Neurofisiología del Control y la Regulación. Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Calz. México-Xochimilco 101, Col. San Lorenzo Huipulco, Tlalpan, Ciudad de México 14370, Mexico.
| | - G Fernando Moreno-Pérez
- Laboratorio de Neurofarmacología de Productos Naturales, Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Calz. México-Xochimilco 101, Col. San Lorenzo Huipulco, Tlalpan, Ciudad de México 14370, Mexico.
| | - Alberto Hernandez-Leon
- Laboratorio de Neurofarmacología de Productos Naturales, Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Calz. México-Xochimilco 101, Col. San Lorenzo Huipulco, Tlalpan, Ciudad de México 14370, Mexico.
| | - Hugo Fernando Narváez-González
- Centro Médico Nacional 20 de Noviembre, Félix Cuevas 540, Col. Del Valle Sur, Benito Juárez, Ciudad de México 03104, Mexico; Hospital de Especialidades Dr. Belisario Domínguez, Av. Tláhuac 4866, San Lorenzo Tezonco, Iztapalapa, Ciudad de México 09930, Mexico.
| | - Rosa Ventura-Martínez
- Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, Av. Universidad No. 3000, Col. Ciudad Universitaria, Alcaldía Coyoacán, Ciudad de México 04510, Mexico.
| | - Francisco Pellicer
- Laboratorio de Neurofarmacología de Productos Naturales, Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Calz. México-Xochimilco 101, Col. San Lorenzo Huipulco, Tlalpan, Ciudad de México 14370, Mexico.
| | - Francisco Javier López-Muñoz
- Laboratorio de dolor y analgesia, Centro de Investigación y de Estudios Avanzados-Sede Sur, Calz. De los Tenorios. Tlalpan, Ciudad de México 14330, Mexico.
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Nong W, Wei H, Dou S, He L, Lin L, Lu D, Wei B, Zhang S, Huo P, Dong M. The NLRP3 activation-related signature predicts the diagnosis and indicates immune characteristics in endometriosis. J Reprod Immunol 2025; 168:104443. [PMID: 39904070 DOI: 10.1016/j.jri.2025.104443] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2024] [Revised: 01/19/2025] [Accepted: 01/24/2025] [Indexed: 02/06/2025]
Abstract
Endometriosis (EMS) is a prevalent gynecological disease that leads to chronic pelvic pain and infertility in women of reproductive age. However, the underlying pathogenic genes and effective treatment for EMS remain unclear. Therefore, this study aims to identify key genes influencing the diagnosis and treatment of EMS. The GSE7307 dataset, comprising 18 EMS and 23 control samples, was obtained from the GEO database. Fourteen differential genes related to NOD-like receptor protein 3 (NLRP3) activation and EMS were extracted from endometrial samples in GSE7307 through differential analysis. GO and KEGG analyses revealed that these genes were primarily involved in the production and regulation of the cytokine IL-1β and the NOD-like receptor signaling pathway. Random Forest (RF) and support vector machine recursive feature elimination algorithms were employed to select four diagnostic markers related to NLRP3 activation (NLRP3, IL-1β, LY96, and PDIA3) for constructing the EMS diagnostic model. These markers were validated using western blotting and tested in GSE7305 and GSE23339 datasets. The AUC values demonstrated the model's robust diagnostic performance. Additionally, the infiltration of immune cells in the samples and the correlation between different immune factors and diagnostic markers were explored. These results suggest that the four diagnostic markers may also play a crucial role in EMS immunity. Finally, the DrugBank database indicated that niclosamide could be effective for NLRP3-targeted therapy. In conclusion, we identified four key diagnostic genes for EMS, and niclosamide emerged as a potential drug for NLRP3-targeted therapy in EMS.
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Affiliation(s)
- Weihua Nong
- Department of Obstetrics and Gynecology, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China; Reproductive Medicine, Guangxi Medical and Health Key Discipline Construction Project of the Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China; Modern Industrial College of Biomedicine and Great Health, Youjiang Medical University for Nationalities, Baise, China.
| | - Huimei Wei
- Department of Reproductive Medical Center, The Affiliated Hospital of Guilin Medical University, Guilin, China; Department of Gynecology, Maoming People's Hospital, Maoming, China.
| | - Sheng Dou
- Reproductive Medicine, Guangxi Medical and Health Key Discipline Construction Project of the Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.
| | - Liqiao He
- Department of Obstetrics and Gynecology, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.
| | - Luping Lin
- Department of Obstetrics and Gynecology, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.
| | - Donglin Lu
- Department of Obstetrics and Gynecology, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.
| | - Bixiao Wei
- Clinical Laboratory, The People's Hospital of Baise, Baise, China.
| | - Shun Zhang
- Department of Reproductive Medical Center, The Affiliated Hospital of Guilin Medical University, Guilin, China.
| | - Peng Huo
- School of Public Health, Guilin Medical University, Guilin, China.
| | - Mingyou Dong
- Reproductive Medicine, Guangxi Medical and Health Key Discipline Construction Project of the Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China; Modern Industrial College of Biomedicine and Great Health, Youjiang Medical University for Nationalities, Baise, China.
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Khan MZ, Chen W, Liu X, Kou X, Khan A, Khan RU, Zahoor M, Wang C. An Overview of Bioactive Compounds' Role in Modulating the Nrf2/Keap1/NF-κB Pathway to Alleviate Lipopolysaccharide-Induced Endometritis. Int J Mol Sci 2024; 25:10319. [PMID: 39408650 PMCID: PMC11476794 DOI: 10.3390/ijms251910319] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2024] [Revised: 09/16/2024] [Accepted: 09/21/2024] [Indexed: 10/19/2024] Open
Abstract
Endometritis is a common inflammatory condition of the uterine endometrial lining that primarily affects perinatal dairy animals and causes significant economic losses in agriculture. It is usually triggered by pathogenic bacteria and is associated with chronic postpartum reproductive tract infections. Bacterial lipopolysaccharides (LPSs) are known to increase levels of reactive oxygen species (ROS), leading to oxidative stress and inflammation through the activation of the NF-κB signaling pathway and the inhibition of Nrf2 nuclear translocation, which regulates antioxidant response elements (AREs). The effectiveness of the conventional management strategy involving antibiotics is decreasing due to resistance and residual concerns. This review explores the potential therapeutic benefits of targeting the Nrf2/Kelch-like ECH-associated protein 1 (Keap1)/NF-κB signaling pathway to alleviate LPS-induced endometritis. We discuss recent advancements in veterinary medicine that utilize exogenous antioxidants to modulate these pathways, thereby reducing oxidative stress and inflammatory responses in endometrial cells. This review highlights the efficacy of several bioactive compounds that enhance Nrf2 signaling and suppress NF-κB activation, offering protective effects against oxidative damage and inflammation. By examining various in vitro studies, this review emphasizes the emerging role of these signaling pathways in developing new therapeutic strategies that could potentially replace or supplement traditional treatments and mitigate the economic impacts of endometritis in livestock.
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Affiliation(s)
- Muhammad Zahoor Khan
- College of Agricultural Science and Engineering, Liaocheng University, Liaocheng 522000, China
| | - Wenting Chen
- College of Agricultural Science and Engineering, Liaocheng University, Liaocheng 522000, China
| | - Xiaotong Liu
- College of Agricultural Science and Engineering, Liaocheng University, Liaocheng 522000, China
| | - Xiyan Kou
- College of Agricultural Science and Engineering, Liaocheng University, Liaocheng 522000, China
| | - Adnan Khan
- Animal Genomics Laboratory, School of Agriculture and Food Science, University College Dublin, D04 V1W8 Dublin, Ireland
| | - Rahat Ullah Khan
- CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, CAS-TWAS Center of Excellence for Emerging Infectious Diseases, Chinese Academy of Sciences, Beijing 100101, China
| | - Muhammad Zahoor
- Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Sognsvannsveien, 90372 Oslo, Norway
| | - Changfa Wang
- College of Agricultural Science and Engineering, Liaocheng University, Liaocheng 522000, China
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Petrikonis K, Bernatoniene J, Kopustinskiene DM, Casale R, Davinelli S, Saso L. The Antinociceptive Role of Nrf2 in Neuropathic Pain: From Mechanisms to Clinical Perspectives. Pharmaceutics 2024; 16:1068. [PMID: 39204413 PMCID: PMC11358986 DOI: 10.3390/pharmaceutics16081068] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2024] [Revised: 08/10/2024] [Accepted: 08/13/2024] [Indexed: 09/04/2024] Open
Abstract
Neuropathic pain, a chronic condition resulting from nerve injury or dysfunction, presents significant therapeutic challenges and is closely associated with oxidative stress and inflammation, both of which can lead to mitochondrial dysfunction. The nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, a critical cellular defense mechanism against oxidative stress, has emerged as a promising target for neuropathic pain management. Nrf2 modulators enhance the expression of antioxidant and cytoprotective genes, thereby reducing oxidative damage, inflammation, and mitochondrial impairment. This review explores the antinociceptive effects of Nrf2, highlighting how pharmacological agents and natural compounds may be used as potential therapeutic strategies against neuropathic pain. Although preclinical studies demonstrate significant pain reduction and improved nerve function through Nrf2 activation, several clinical challenges need to be addressed. However, emerging clinical evidence suggests potential benefits of Nrf2 modulators in several conditions, such as diabetic neuropathy and multiple sclerosis. Future research should focus on further elucidating the molecular role of Nrf2 in neuropathic pain to optimize its modulation efficacy and maximize clinical utility.
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Affiliation(s)
- Kestutis Petrikonis
- Department of Neurology, Lithuanian University of Health Sciences, Eivenių Str. 2, LT-50009 Kaunas, Lithuania;
| | - Jurga Bernatoniene
- Department of Drug Technology and Social Pharmacy, Faculty of Pharmacy, Medical Academy, Lithuanian University of Health Sciences, Sukileliu pr. 13, LT-50161 Kaunas, Lithuania
- Institute of Pharmaceutical Technologies, Faculty of Pharmacy, Medical Academy, Lithuanian University of Health Sciences, Sukileliu pr. 13, LT-50161 Kaunas, Lithuania;
| | - Dalia M. Kopustinskiene
- Institute of Pharmaceutical Technologies, Faculty of Pharmacy, Medical Academy, Lithuanian University of Health Sciences, Sukileliu pr. 13, LT-50161 Kaunas, Lithuania;
| | - Roberto Casale
- Opusmedica Persons, Care & Research-NPO, 29121 Piacenza, Italy;
| | - Sergio Davinelli
- Department of Medicine and Health Sciences “V. Tiberio”, University of Molise, 86100 Campobasso, Italy;
| | - Luciano Saso
- Department of Physiology and Pharmacology “Vittorio Erspamer”, La Sapienza University, 00185 Rome, Italy;
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Papini JZB, de Assis Esteves B, de Souza Oliveira VG, Abdalla HB, Cereda CMS, de Araújo DR, Tofoli GR. Analgesic Effect of Sulforaphane: A New Application for Poloxamer-Hyaluronic Acid Hydrogels. Gels 2024; 10:460. [PMID: 39057483 PMCID: PMC11276367 DOI: 10.3390/gels10070460] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2024] [Revised: 07/08/2024] [Accepted: 07/11/2024] [Indexed: 07/28/2024] Open
Abstract
Sulforaphane (SFN) has shown potential as an antioxidant and anti-inflammatory agent. To improve its druggability, we developed new analgesic formulations with sulforaphane-loaded hyaluronic acid (HA)-poloxamer (PL) hydrogel. This study evaluated the pre-clinical safety and effectiveness of these formulations. Effectiveness was tested on Wistar rats divided into groups (n = 15) receiving (IM, 10 mg/kg) SFN formulations or control groups (without SFN). This study used a hind paw incision postoperative pain model to evaluate mechanical hypersensitivity with von Frey filaments. TNF-α, IL-1β, substance P, and CGRP levels verified anti-inflammatory activity in the hind paw tissue. Histopathology of tissues surrounding the injection site was assessed after 2 and 7 days post-treatment. To corroborate drug safety, cell viability of 3T3 and RAW 264.7 cultures was assessed. Additionally, RAW 264.7 cultures primed with carrageenan evaluated nitric oxide (NO) levels. All animals exhibited post-incisional hypersensitivity, and F2 (PL 407/338 (18/2%) + HA 1% + SFN 0.1%) showed a longer analgesic effect (p < 0.05). F2 reduced TNF-α, IL-1β, and CGRP levels (p < 0.05). Histopathological evaluation showed mild to moderate inflammatory reactions after the formulations' injections. F2 produced no significant difference in cell viability (p > 0.05) but reduced NO production (p < 0.05). Thus, our results highlight the biocompatibility and effectiveness of F2.
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Affiliation(s)
- Juliana Zampoli Boava Papini
- Faculdade São Leopoldo Mandic, Instituto de Pesquisa São Leopoldo Mandic, Rua José Rocha Junqueira 13, Campinas 13045-75, SP, Brazil
| | - Bruno de Assis Esteves
- Faculdade São Leopoldo Mandic, Instituto de Pesquisa São Leopoldo Mandic, Rua José Rocha Junqueira 13, Campinas 13045-75, SP, Brazil
| | - Vagner Gomes de Souza Oliveira
- Faculdade São Leopoldo Mandic, Instituto de Pesquisa São Leopoldo Mandic, Rua José Rocha Junqueira 13, Campinas 13045-75, SP, Brazil
| | - Henrique Ballassani Abdalla
- Faculdade São Leopoldo Mandic, Instituto de Pesquisa São Leopoldo Mandic, Rua José Rocha Junqueira 13, Campinas 13045-75, SP, Brazil
| | - Cintia Maria Saia Cereda
- Faculdade São Leopoldo Mandic, Instituto de Pesquisa São Leopoldo Mandic, Rua José Rocha Junqueira 13, Campinas 13045-75, SP, Brazil
| | - Daniele Ribeiro de Araújo
- Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Av. dos Estados, 5001. Bloco A, Torre 3, Santo André 09210-580, SP, Brazil;
- Escola Paulista de Medicina, Departamento de Biofísica, Universidade Federal de São Paulo, Rua Botucatu, 862, Vila Clementino, Sao Paulo 04023-062, SP, Brazil
| | - Giovana Radomille Tofoli
- Faculdade São Leopoldo Mandic, Instituto de Pesquisa São Leopoldo Mandic, Rua José Rocha Junqueira 13, Campinas 13045-75, SP, Brazil
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García-Izquierdo L, Marín-Sánchez P, García-Peñarrubia P, Martínez-Esparza M. New Potential Pharmacological Options for Endometriosis Associated Pain. Int J Mol Sci 2024; 25:7068. [PMID: 39000175 PMCID: PMC11240985 DOI: 10.3390/ijms25137068] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Revised: 06/22/2024] [Accepted: 06/26/2024] [Indexed: 07/16/2024] Open
Abstract
Endometriosis is a chronic inflammatory disorder characterized by the abnormal growth of endometrial-like tissue outside the uterine cavity, affecting 10-15% of women of reproductive age. Pain is the most common symptom. Treatment options include surgery, which has limited effectiveness and high recurrence rates, and pharmacotherapy. Hormonal therapies, commonly used for symptom management, can have side effects and contraceptive outcomes, contributing to the infertility associated with endometriosis, with pain and lesions often reappearing after treatment cessation. Among its etiological factors, immunological and inflammatory dysregulation plays a significant role, representing an interesting target for developing new therapeutic strategies. This review critically analyzes recent studies to provide an updated synthesis of ongoing research into potential new pharmacotherapies focusing on lesion progression, pain relief, and improving quality of life. Immunotherapy, natural anti-inflammatory and antioxidant compounds and drug repurposing show promise in addressing the limitations of current treatments by targeting immunological factors, potentially offering non-invasive solutions for managing pain and infertility in endometriosis. Promising results have been obtained from in vitro and animal model studies, but clinical trials are still limited. More effort is needed to translate these findings into clinical practice to effectively reduce disease progression, alleviate pain symptoms and preserve the reproductive capacity, improving patients' overall wellbeing.
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Affiliation(s)
- Laura García-Izquierdo
- Department of Biochemistry, Molecular Biology (B) and Immunology, Faculty of Medicine, Regional Campus of International Excellence "Campus Mare Nostrum", University of Murcia and Biomedical Research Institute of Murcia (IMIB), 30120 Murcia, Spain
| | - Pilar Marín-Sánchez
- Department of Gynaecology and Obstetrics, Hospital General Universitario Santa Lucía, University of Murcia and Biomedical Research Institute of Murcia (IMIB), 30120 Murcia, Spain
| | - Pilar García-Peñarrubia
- Department of Biochemistry, Molecular Biology (B) and Immunology, Faculty of Medicine, Regional Campus of International Excellence "Campus Mare Nostrum", University of Murcia and Biomedical Research Institute of Murcia (IMIB), 30120 Murcia, Spain
| | - María Martínez-Esparza
- Department of Biochemistry, Molecular Biology (B) and Immunology, Faculty of Medicine, Regional Campus of International Excellence "Campus Mare Nostrum", University of Murcia and Biomedical Research Institute of Murcia (IMIB), 30120 Murcia, Spain
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Habtemariam S. Anti-Inflammatory Therapeutic Mechanisms of Isothiocyanates: Insights from Sulforaphane. Biomedicines 2024; 12:1169. [PMID: 38927376 PMCID: PMC11200786 DOI: 10.3390/biomedicines12061169] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Revised: 05/16/2024] [Accepted: 05/21/2024] [Indexed: 06/28/2024] Open
Abstract
Isothiocyanates (ITCs) belong to a group of natural products that possess a highly reactive electrophilic -N=C=S functional group. They are stored in plants as precursor molecules, glucosinolates, which are processed by the tyrosinase enzyme upon plant tissue damage to release ITCs, along with other products. Isolated from broccoli, sulforaphane is by far the most studied antioxidant ITC, acting primarily through the induction of a transcription factor, the nuclear factor erythroid 2-related factor 2 (Nrf2), which upregulates downstream antioxidant genes/proteins. Paradoxically, sulforaphane, as a pro-oxidant compound, can also increase the levels of reactive oxygen species, a mechanism which is attributed to its anticancer effect. Beyond highlighting the common pro-oxidant and antioxidant effects of sulforaphane, the present paper was designed to assess the diverse anti-inflammatory mechanisms reported to date using a variety of in vitro and in vivo experimental models. Sulforaphane downregulates the expression of pro-inflammatory cytokines, chemokines, adhesion molecules, cycloxyhenase-2, and inducible nitric oxide synthase. The signalling pathways of nuclear factor κB, activator protein 1, sirtuins 1, silent information regulator sirtuin 1 and 3, and microRNAs are among those affected by sulforaphane. These anti-inflammatory actions are sometimes due to direct action via interaction with the sulfhydryl structural moiety of cysteine residues in enzymes/proteins. The following are among the topics discussed in this paper: paradoxical signalling pathways such as the immunosuppressant or immunostimulant mechanisms; crosstalk between the oxidative and inflammatory pathways; and effects dependent on health and disease states.
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Affiliation(s)
- Solomon Habtemariam
- Pharmacognosy Research & Herbal Analysis Services UK, University of Greenwich, Central Avenue, Chatham-Maritime, Kent ME4 4TB, UK
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Malinauskiene V, Zuzo A, Liakina V, Kazenaite E, Stundiene I. Menstrual cycle abnormalities in women with inflammatory bowel disease and effects of biological therapy on gynecological pathology. World J Clin Cases 2023; 11:4989-4995. [PMID: 37583859 PMCID: PMC10424016 DOI: 10.12998/wjcc.v11.i21.4989] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Revised: 06/14/2023] [Accepted: 06/30/2023] [Indexed: 07/26/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic condition that affects young individuals in their reproductive years. It may have long-term implications on their reproductive, sexual, and mental health. IBD has been related to menstrual abnormalities. Furthermore, the administration of biological therapy can also result in gynecological issues in addition to the disease itself. The purpose of this review was to present potential menstrual cycle problems in patients with IBD, as well as the impact of adalimumab and other anti-tumor necrosis factor medications on gynecological pathology.
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Affiliation(s)
- Vaidota Malinauskiene
- Clinic of Gastroenterology, Nephrourology and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius 01513, Lithuania
| | - Anastasija Zuzo
- Faculty of Medicine, Vilnius University, Vilnius 01513, Lithuania
| | - Valentina Liakina
- Clinic of Gastroenterology, Nephrourology and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius 01513, Lithuania
- Department of Chemistry and Bioengineering, Faculty of Fundamental Sciences, Vilnius Tech, Vilnius 10223, Lithuania
| | - Edita Kazenaite
- Clinic of Gastroenterology, Nephrourology and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius 01513, Lithuania
| | - Ieva Stundiene
- Clinic of Gastroenterology, Nephrourology and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius 01513, Lithuania
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Neto AC, Santos-Pereira M, Abreu-Mendes P, Neves D, Almeida H, Cruz F, Charrua A. The Unmet Needs for Studying Chronic Pelvic/Visceral Pain Using Animal Models. Biomedicines 2023; 11:biomedicines11030696. [PMID: 36979674 PMCID: PMC10045296 DOI: 10.3390/biomedicines11030696] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Revised: 02/13/2023] [Accepted: 02/16/2023] [Indexed: 03/03/2023] Open
Abstract
The different definitions of chronic pelvic/visceral pain used by international societies have changed over the years. These differences have a great impact on the way researchers study chronic pelvic/visceral pain. Recently, the role of systemic changes, including the role of the central nervous system, in the perpetuation and chronification of pelvic/visceral pain has gained weight. Consequently, researchers are using animal models that resemble those systemic changes rather than using models that are organ- or tissue-specific. In this review, we discuss the advantages and disadvantages of using bladder-centric and systemic models, enumerating some of the central nervous system changes and pain-related behaviors occurring in each model. We also present some drawbacks when using animal models and pain-related behavior tests and raise questions about possible, yet to be demonstrated, investigator-related bias. We also suggest new approaches to study chronic pelvic/visceral pain by refining existing animal models or using new ones.
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Affiliation(s)
- Ana Catarina Neto
- Experimental Biology Unit, Department of Biomedicine, Faculty of Medicine of University of Porto, 4200-319 Porto, Portugal
- I3S—Instituto de Investigação e Inovação em Saúde, University of Porto, 4200-135 Porto, Portugal
| | - Mariana Santos-Pereira
- Experimental Biology Unit, Department of Biomedicine, Faculty of Medicine of University of Porto, 4200-319 Porto, Portugal
- I3S—Instituto de Investigação e Inovação em Saúde, University of Porto, 4200-135 Porto, Portugal
| | - Pedro Abreu-Mendes
- I3S—Instituto de Investigação e Inovação em Saúde, University of Porto, 4200-135 Porto, Portugal
- Department of Urology, Centro Hospitalar de São João, 4200-319 Porto, Portugal
- Physiology and Surgery Department, Faculty of Medicine of University of Porto, 4200-319 Porto, Portugal
| | - Delminda Neves
- Experimental Biology Unit, Department of Biomedicine, Faculty of Medicine of University of Porto, 4200-319 Porto, Portugal
- I3S—Instituto de Investigação e Inovação em Saúde, University of Porto, 4200-135 Porto, Portugal
| | - Henrique Almeida
- Experimental Biology Unit, Department of Biomedicine, Faculty of Medicine of University of Porto, 4200-319 Porto, Portugal
- I3S—Instituto de Investigação e Inovação em Saúde, University of Porto, 4200-135 Porto, Portugal
- Ginecologia-Obstetrícia, Hospital-CUF Porto, 4100-180 Porto, Portugal
| | - Francisco Cruz
- I3S—Instituto de Investigação e Inovação em Saúde, University of Porto, 4200-135 Porto, Portugal
- Department of Urology, Centro Hospitalar de São João, 4200-319 Porto, Portugal
- Physiology and Surgery Department, Faculty of Medicine of University of Porto, 4200-319 Porto, Portugal
| | - Ana Charrua
- Experimental Biology Unit, Department of Biomedicine, Faculty of Medicine of University of Porto, 4200-319 Porto, Portugal
- I3S—Instituto de Investigação e Inovação em Saúde, University of Porto, 4200-135 Porto, Portugal
- Correspondence:
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Luan Y, Luo Y, Deng M. New advances in Nrf2-mediated analgesic drugs. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2023; 110:154598. [PMID: 36603339 DOI: 10.1016/j.phymed.2022.154598] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/21/2022] [Revised: 11/24/2022] [Accepted: 12/10/2022] [Indexed: 06/17/2023]
Abstract
BACKGROUND Oxidative stress is an inevitable process that occurs during life activities, and it can participate in the development of inflammation. Although great progress has been made according to research examining analgesic drugs and therapies, there remains a need to develop new analgesic drugs to fill certain gaps in both the experimental and clinical space. PURPOSE This review reports the research and preclinical progress of this class of analgesics by summarizing known nuclear factor E-2-related factor-2 (Nrf2) pathway-modulating substances. STUDY DESIGN We searched and reported experiments that intervene in the Nrf2 pathway and its various upstream and downstream molecules for analgesic therapy. METHODS The medical literature database (PubMed) was searched for experimental studies examining the reduction of pain in animals through the Nrf2 pathway, the research methods were analyzed, and the pathways were classified and reported according to the pathway of these experimental interventions. RESULTS Humans have identified a variety of substances that can fight pain by regulating the expression of Nrf2 and its upstream and downstream pathways. CONCLUSION The Nrf2 pathway exerts anti-inflammatory activity by regulating oxidative stress, thereby playing a role in the fight against pain.
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Affiliation(s)
- Yifan Luan
- Department of Biochemistry and Molecular Biology & Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, Hunan 410013, China; Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, China; Hunan Key Laboratory of Animal Models for Human Diseases, Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan 410013, China
| | - Yaping Luo
- Department of Biochemistry and Molecular Biology & Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, Hunan 410013, China; Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, China; Hunan Key Laboratory of Animal Models for Human Diseases, Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan 410013, China
| | - Meichun Deng
- Department of Biochemistry and Molecular Biology & Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, Hunan 410013, China; Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, China; Hunan Key Laboratory of Animal Models for Human Diseases, Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan 410013, China.
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11
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Wang Q, Botchway BOA, Zhang Y, Liu X. Ellagic acid activates the Keap1-Nrf2-ARE signaling pathway in improving Parkinson's disease: A review. Biomed Pharmacother 2022; 156:113848. [PMID: 36242848 DOI: 10.1016/j.biopha.2022.113848] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Revised: 09/26/2022] [Accepted: 10/06/2022] [Indexed: 12/14/2022] Open
Abstract
Parkinson's disease (PD) is a familiar neurodegenerative disease, accompanied by motor retardation, static tremor, memory decline and dementia. Heredity, environment, age and oxidative stress have been suggested as key factors in the instigation of PD. The Keap1-Nrf2-ARE signaling is one of the most significant anti- oxidative stress (OS) pathways. The Keap1 is a negative regulator of the Nrf2. The Keap1-Nrf2-ARE pathway can induce cell oxidation resistance and reduce nerve injury to treat neurodegenerative diseases. Ellagic acid (EA) can inhibit the Keap1 to accumulate the Nrf2 in the nucleus, and act on the ARE to produce target proteins, which in turn may alleviate the impact of OS on neuronal cells of PD. This review analyzes the structure and physiological role of EA, along with the structure, composition and functions of the Keap1-Nrf2-ARE signaling pathway. We further expound on the mechanism of ellagic acid in its activation of the Keap1-Nrf2-ARE signaling pathway, as well as the relationship between EA in impairing the TLR4/Myd88/NF-κB and Nrf2 pathways. Ellagic acid has the potentiality of improving PD by activating the Keap1-Nrf2-ARE signaling pathway and scavenging free radicals.
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Affiliation(s)
- Qianhui Wang
- Department of Histology and Embryology, Medical College, Shaoxing University, Zhejiang, China
| | - Benson O A Botchway
- Institute of Neuroscience, Zhejiang University School of Medicine, Hangzhou, China
| | - Yong Zhang
- Department of Histology and Embryology, Medical College, Shaoxing University, Zhejiang, China
| | - Xuehong Liu
- Department of Histology and Embryology, Medical College, Shaoxing University, Zhejiang, China.
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Ramírez-Pavez T, García-Peñaranda A, Garcia-Ibañez P, Yepes-Molina L, Carvajal M, Ruiz-Alcaraz AJ, Moreno DA, García-Peñarrubia P, Martínez-Esparza M. Potential of Sulforaphane and Broccoli Membrane Vesicles as Regulators of M1/M2 Human Macrophage Activity. Int J Mol Sci 2022; 23:ijms231911141. [PMID: 36232440 PMCID: PMC9570499 DOI: 10.3390/ijms231911141] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2022] [Revised: 09/14/2022] [Accepted: 09/16/2022] [Indexed: 11/30/2022] Open
Abstract
Macrophages have emerged as important therapeutic targets in many human diseases. The aim of this study was to analyze the effect of broccoli membrane vesicles and sulphoraphane (SFN), either free or encapsulated, on the activity of human monocyte-derived M1 and M2 macrophage primary culture. Our results show that exposure for 24 h to SFN 25 µM, free and encapsulated, induced a potent reduction on the activity of human M1 and M2 macrophages, downregulating proinflammatory and anti-inflammatory cytokines and phagocytic capability on C. albicans. The broccoli membrane vesicles do not represent inert nanocarriers, as they have low amounts of bioactive compounds, being able to modulate the cytokine production, depending on the inflammatory state of the cells. They could induce opposite effects to that of higher doses of SFN, reflecting its hormetic effect. These data reinforce the potential use of broccoli compounds as therapeutic agents not only for inflammatory diseases, but they also open new clinical possibilities for applications in other diseases related to immunodeficiency, autoimmunity, or in cancer therapy. Considering the variability of their biological effects in different scenarios, a proper therapeutic strategy with Brassica bioactive compounds should be designed for each pathology.
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Affiliation(s)
- Tamara Ramírez-Pavez
- Biochemistry and Molecular Biology (B) and Immunology Department, School of Medicine, IMIB and Regional Campus of International Excellence “Campus Mare Nostrum”, Universidad de Murcia, 30100 Murcia, Spain
| | - Andrea García-Peñaranda
- Biochemistry and Molecular Biology (B) and Immunology Department, School of Medicine, IMIB and Regional Campus of International Excellence “Campus Mare Nostrum”, Universidad de Murcia, 30100 Murcia, Spain
| | - Paula Garcia-Ibañez
- Aquaporins Group, Centro de Edafología y Biología Aplicada del Segura (CEBAS-CSIC), Campus de Espinardo, 30100 Murcia, Spain
| | - Lucía Yepes-Molina
- Aquaporins Group, Centro de Edafología y Biología Aplicada del Segura (CEBAS-CSIC), Campus de Espinardo, 30100 Murcia, Spain
| | - Micaela Carvajal
- Aquaporins Group, Centro de Edafología y Biología Aplicada del Segura (CEBAS-CSIC), Campus de Espinardo, 30100 Murcia, Spain
| | - Antonio J. Ruiz-Alcaraz
- Biochemistry and Molecular Biology (B) and Immunology Department, School of Medicine, IMIB and Regional Campus of International Excellence “Campus Mare Nostrum”, Universidad de Murcia, 30100 Murcia, Spain
| | - Diego A. Moreno
- Phytochemistry and Healthy Food Lab (LabFAS), Department of Food Science Technology, Centro de Edafología y Biología Aplicada del Segura (CEBAS-CSIC), Campus de Espinardo, 30100 Murcia, Spain
| | - Pilar García-Peñarrubia
- Biochemistry and Molecular Biology (B) and Immunology Department, School of Medicine, IMIB and Regional Campus of International Excellence “Campus Mare Nostrum”, Universidad de Murcia, 30100 Murcia, Spain
| | - María Martínez-Esparza
- Biochemistry and Molecular Biology (B) and Immunology Department, School of Medicine, IMIB and Regional Campus of International Excellence “Campus Mare Nostrum”, Universidad de Murcia, 30100 Murcia, Spain
- Correspondence: ; Tel.: +34-868883989
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Liang W, Greven J, Fragoulis A, Horst K, Bläsius F, Wruck C, Pufe T, Kobbe P, Hildebrand F, Lichte P. Sulforaphane-Dependent Up-Regulation of NRF2 Activity Alleviates Both Systemic Inflammatory Response and Lung Injury After Hemorrhagic Shock/Resuscitation in Mice. Shock 2022; 57:221-229. [PMID: 34559743 DOI: 10.1097/shk.0000000000001859] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
ABSTRACT Hemorrhagic shock/resuscitation (HS/R) is closely associated with overwhelming oxidative stress and systemic inflammation. As an effective activator of the nuclear factor-erythroid factor 2 related factor 2 (Nrf2) pathway, sulforaphane (SFN) exerts antioxidant and anti-inflammatory effects. We explored SFN's effects on alveolar macrophages (AMs), systemic inflammation, and pulmonary damage in an isolated murine HS/R model. Male C57/BL6 wild type and transgenic antioxidant response element (ARE)-luciferase (luc) mice (both n = 6 per group) were exposed to either pressure-controlled HS/R (mean arterial pressure 35-45 mm Hg for 90 min) or sham procedure (surgery without HS/R) or were sacrificed without intervention (control group). Fluid resuscitation was performed via the reinfusion of withdrawn blood and 0.9% saline. Sulforaphane or 0.9% saline (vehicle) was administrated intraperitoneally. Mice were sacrificed 6, 24, or 72 h after resuscitation. Bioluminescence imaging of ARE-luc mice was conducted to measure pulmonary Nrf2 activity. Plasma was collected to determine systemic cytokine levels. Alveolar macrophages were isolated before measuring cytokines in the supernatant and performing immunofluorescence staining, as well as Western blot for intracellular Nrf2. Histological damage was assessed via the acute lung injury score and wet/dry ratio.Hemorrhagic shock/resuscitation was associated with pulmonary Nrf2 activation. Sulforaphane enhanced pulmonary Nrf2 activity and the Nrf2 activation of AM, while it decreased lung damage. Sulforaphane exerted down-regulatory effects on AM-generated and systemic pro-inflammatory mediators, while it did not have such effects on IL-10.In conclusion, SFN beneficially enhances pulmonary Nrf2 activity and promotes Nrf2 accumulation in AMs' nuclei. This may exert not only local protective effects but also systemic effects via the down-regulation of pro-inflammatory cytokines. The administration of Nrf2 activator post-HS/R may represent an innovative treatment strategy.
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Affiliation(s)
- Weiqiang Liang
- Department of Orthopedics, Trauma and Reconstructive Surgery, University Hospital RWTH Aachen, Aachen, Germany
- Department of Bone and Joint Surgery, The First Affiliated Hospital of Shandong First Medical University, Jinan City, Shandong Province, PR China
| | - Johannes Greven
- Department of Orthopedics, Trauma and Reconstructive Surgery, University Hospital RWTH Aachen, Aachen, Germany
| | - Athanassios Fragoulis
- Department of Anatomy and Cell Biology, RWTH Aachen University, Wendlingweg 2, Aachen, Germany
| | - Klemens Horst
- Department of Orthopedics, Trauma and Reconstructive Surgery, University Hospital RWTH Aachen, Aachen, Germany
| | - Felix Bläsius
- Department of Orthopedics, Trauma and Reconstructive Surgery, University Hospital RWTH Aachen, Aachen, Germany
| | - Christoph Wruck
- Department of Anatomy and Cell Biology, RWTH Aachen University, Wendlingweg 2, Aachen, Germany
| | - Thomas Pufe
- Department of Anatomy and Cell Biology, RWTH Aachen University, Wendlingweg 2, Aachen, Germany
| | - Philipp Kobbe
- Department of Orthopedics, Trauma and Reconstructive Surgery, University Hospital RWTH Aachen, Aachen, Germany
| | - Frank Hildebrand
- Department of Orthopedics, Trauma and Reconstructive Surgery, University Hospital RWTH Aachen, Aachen, Germany
| | - Philipp Lichte
- Department of Orthopedics, Trauma and Reconstructive Surgery, University Hospital RWTH Aachen, Aachen, Germany
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Alyoussef A. Attenuation of experimentally induced atopic dermatitis in mice by sulforaphane: effect on inflammation and apoptosis. Toxicol Mech Methods 2021; 32:224-232. [PMID: 34651546 DOI: 10.1080/15376516.2021.1994076] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Atopic dermatitis (AD) is characterized by progressive skin inflammation. In addition, sulforaphane is an isothiocyanate organosulfur compound from cruciferous vegetables. Sulforaphane was reported to ameliorate inflammatory responses. Therefore, this study was conducted to evaluate the protective effects of sulforaphane in AD through affecting the balance between pro-inflammatory and anti-inflammatory cytokines and to evaluate its effect on AD-induced activation of the apoptotic pathway. The method of repeated rubbing of 2,4-dinitrochlorobenzene (DNCB) on shaved dorsal skin and ears of mice was used for induction of AD. After the development of AD, part of the mice was injected with 1 mg/kg sulforaphane, subcutaneously three times weekly. Samples of skin were isolated for assessment of gene and protein expression of 8-hydroxy2'-deoxyguanosine, IgE, NFκB, TNF-α, IL-1β, IL-4, IL-10, Nrf2, and caspase-3. In addition, skin sections from different groups were stained with anti-caspase-3 antibodies. Mice in the AD group were characterized by increased gene and protein expression of 8-hydroxy2'-deoxyguanosine, IgE, NFκB, TNF-α, IL-1β, and caspase-3 associated with reduced expression of Nrf2, IL-4, and IL-10. Treatment of AD mice with sulforaphane significantly reduced the number of scratches, dermatitis score, and ear thickness. In addition, sulforaphane significantly attenuated the gene and protein expressions produced by AD. Therefore, sulforaphane alleviated AD induced in mice through inhibition of oxidative stress, oxidative DNA damage, inflammation, and apoptosis. HIGHLIGHTSAtopic dermatitis is a chronic relapsing inflammatory disease.Sulforaphane is an isothiocyanate organosulfur compound obtained from cruciferous vegetables.Sulforaphane alleviated AD induced in mice.Sulforaphane inhibits oxidative stress, oxidative DNA damage, inflammation, and apoptosis.
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Affiliation(s)
- Abdullah Alyoussef
- Department of Internal Medicine (Dermatology), Faculty of Medicine, University of Tabuk, Tabuk, Saudi Arabia
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15
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Zhou YQ, Mei W, Tian XB, Tian YK, Liu DQ, Ye DW. The therapeutic potential of Nrf2 inducers in chronic pain: Evidence from preclinical studies. Pharmacol Ther 2021; 225:107846. [PMID: 33819559 DOI: 10.1016/j.pharmthera.2021.107846] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Accepted: 03/29/2021] [Indexed: 02/06/2023]
Abstract
Chronic pain remains an enormous health problem affecting approximatively 30% of the world's population. Opioids as the first line analgesics often leads to undesirable side effects when used long term. Therefore, novel therapeutic targets are urgently needed to the development of more efficacious analgesics. Substantial evidence indicates that excessive reactive oxygen species (ROS) are extremely important to the development of chronic pain. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a master transcription factor regulating endogenous antioxidant defense. Emerging evidence suggests that Nrf2 and its downstream effectors are implicated in chronic inflammatory and neuropathic pain. Notably, controversial results have been reported regarding the expression of Nrf2 and its downstream targets in peripheral and central regions involved in pain transmission. However, our recent studies and results from other laboratories demonstrate that Nrf2 inducers exert potent analgesic effects in various murine models of chronic pain. In this review, we summarized and discussed the preclinical evidence demonstrating the therapeutic potential of Nrf2 inducers in chronic pain. These evidence indicates that Nrf2 activation are beneficial in chronic pain mostly by alleviating ROS-associated pathological processes. Overall, Nrf2-based therapy for chronic pain is an area with great promise, but more research regarding its detailed mechanisms is warranted.
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Affiliation(s)
- Ya-Qun Zhou
- Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Wei Mei
- Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Xue-Bi Tian
- Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Yu-Ke Tian
- Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Dai-Qiang Liu
- Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
| | - Da-Wei Ye
- Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Shanxi Medical University; Tongji Shanxi Hospital, Tongji Medical College, Huazhong University of Science and Technology, Taiyuan, 030032, China; Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
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16
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Cardozo LFMF, Alvarenga LA, Ribeiro M, Dai L, Shiels PG, Stenvinkel P, Lindholm B, Mafra D. Cruciferous vegetables: rationale for exploring potential salutary effects of sulforaphane-rich foods in patients with chronic kidney disease. Nutr Rev 2020; 79:1204-1224. [DOI: 10.1093/nutrit/nuaa129] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Abstract
Sulforaphane (SFN) is a sulfur-containing isothiocyanate found in cruciferous vegetables (Brassicaceae) and a well-known activator of nuclear factor-erythroid 2-related factor 2 (Nrf2), considered a master regulator of cellular antioxidant responses. Patients with chronic diseases, such as diabetes, cardiovascular disease, cancer, and chronic kidney disease (CKD) present with high levels of oxidative stress and a massive inflammatory burden associated with diminished Nrf2 and elevated nuclear transcription factor-κB-κB expression. Because it is a common constituent of dietary vegetables, the salutogenic properties of sulforaphane, especially it’s antioxidative and anti-inflammatory properties, have been explored as a nutritional intervention in a range of diseases of ageing, though data on CKD remain scarce. In this brief review, the effects of SFN as a senotherapeutic agent are described and a rationale is provided for studies that aim to explore the potential benefits of SFN-rich foods in patients with CKD.
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Affiliation(s)
- Ludmila F M F Cardozo
- Graduate Program in Cardiovascular Sciences, Fluminense Federal University, Niterói, Rio de Janeiro, Brazil
| | - Livia A Alvarenga
- Graduate Program in Medical Sciences, Fluminense Federal University, Niterói, Rio de Janeiro, Brazil
| | - Marcia Ribeiro
- Graduate Program in Nutrition Sciences, Fluminense Federal University, Niterói, Rio de Janeiro, Brazil
| | - Lu Dai
- Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Technology and Intervention, Karolinska Institutet, Stockholm, Sweden
| | - Paul G Shiels
- Wolfson Wohl Translational Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland
| | - Peter Stenvinkel
- Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Technology and Intervention, Karolinska Institutet, Stockholm, Sweden
| | - Bengt Lindholm
- Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Technology and Intervention, Karolinska Institutet, Stockholm, Sweden
| | - Denise Mafra
- Graduate Program in Cardiovascular Sciences, Fluminense Federal University, Niterói, Rio de Janeiro, Brazil
- Graduate Program in Medical Sciences, Fluminense Federal University, Niterói, Rio de Janeiro, Brazil
- Graduate Program in Nutrition Sciences, Fluminense Federal University, Niterói, Rio de Janeiro, Brazil
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Brassica Bioactives Could Ameliorate the Chronic Inflammatory Condition of Endometriosis. Int J Mol Sci 2020; 21:ijms21249397. [PMID: 33321760 PMCID: PMC7763502 DOI: 10.3390/ijms21249397] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2020] [Revised: 11/26/2020] [Accepted: 12/05/2020] [Indexed: 02/07/2023] Open
Abstract
Endometriosis is a chronic, inflammatory, hormone-dependent disease characterized by histological lesions produced by the presence of endometrial tissue outside the uterine cavity. Despite the fact that an estimated 176 million women are affected worldwide by this gynecological disorder, risk factors that cause endometriosis have not been properly defined and current treatments are not efficient. Although the interaction between diet and human health has been the focus of many studies, little information about the correlation of foods and their bioactive derivates with endometriosis is available. In this framework, Brassica crops have emerged as potential candidates for ameliorating the chronic inflammatory condition of endometriosis, due to their abundant content of health-promoting compounds such as glucosinolates and their hydrolysis products, isothiocyanates. Several inflammation-related signaling pathways have been included among the known targets of isothiocyanates, but those involving aquaporin water channels have an important role in endometriosis. Therefore, the aim of this review is to highlight the promising effects of the phytochemicals present in Brassica spp. as major candidates for inclusion in a dietary approach aiming to improve the inflammatory condition of women affected with endometriosis. This review points out the potential roles of glucosinolates and isothiocyanates from Brassicas as anti-inflammatory compounds, which might contribute to a reduction in endometriosis symptoms. In view of these promising results, further investigation of the effect of glucosinolates on chronic inflammatory diseases, either as diet coadjuvants or as therapeutic molecules, should be performed. In addition, we highlight the involvement of aquaporins in the maintenance of immune homeostasis. In brief, glucosinolates and the modulation of cellular water by aquaporins could shed light on new approaches to improve the quality of life for women with endometriosis.
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Gandhi J, Wilson AL, Liang R, Weissbart SJ, Khan SA. Sciatic endometriosis: A narrative review of an unusual neurogynecologic condition. JOURNAL OF ENDOMETRIOSIS AND PELVIC PAIN DISORDERS 2020. [DOI: 10.1177/2284026520970813] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Endometriosis is a condition in which there is an ectopic growth of endometrial tissue. Sciatic endometriosis, otherwise known as catamenial sciatica, is a rare but exceedingly significant presentation of endometriosis. Symptoms include cyclic sciatic pain that peaks during the menstrual period; additionally, paresthesia, paresis, and areflexia may occur with this condition. Sciatic endometriosis can be presumptively diagnosed in response to empiric treatment (e.g. gonadotropin-releasing hormone analogs) or imaging studies, but a definitive diagnosis of sciatic endometriosis may occur from examining tissue obtained during surgery. Surgical removal of endometriosis from the sciatic nerve root can potentially eliminate symptoms while maintaining normal reproductive function, though poses particular surgical risks. Familiarity with this rare condition is paramount to making this diagnosis and the initiation of earlier treatment.
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Affiliation(s)
- Jason Gandhi
- Department of Physiology and Biophysics, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, USA
- Medical Student Research Institute, St. George’s University School of Medicine, Grenada, West Indies
| | - Anthony L Wilson
- School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Raymond Liang
- Department of Physiology and Biophysics, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, USA
| | - Steven J Weissbart
- Department of Urology, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, USA
- Women’s Pelvic Health & Continence Center, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, USA
| | - Sardar Ali Khan
- Department of Physiology and Biophysics, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, USA
- Department of Urology, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, USA
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