Rheumatoid arthritis (RA) is an autoimmune disease with an important inflammatory component accompanied by deregulated redox-dependent signaling pathways that are feeding back into inflammation. In this context, we bring into focus the transcription factor NRF2, a master redox regulator that exerts exquisite antioxidant and anti-inflammatory effects. The review does not intend to be exhaustive, but to point out arguments sustaining the rationale for applying an NRF2-directed co-treatment in RA as well as its potential limitations. The involvement of NRF2 in RA is emphasized through an analysis of publicly available transcriptomic data on NRF2 target genes and the findings from NRF2-knockout mice. The impact of NRF2 on concurrent pathologic mechanisms in RA is explained by its crosstalk with major redox-sensitive inflammatory and cell death-related pathways, in the context of the increased survival of pathologic cells in RA. The proposed adjunctive therapy targeted to NRF2 is further sustained by the existence of promising NRF2 activators that are in various stages of drug development. The interference of NRF2 with conventional anti-rheumatic therapies is discussed, including the cytoprotective effects of NRF2 for alleviating drug toxicity. From another perspective, the review presents how NRF2 activation would be decreasing the efficacy of synthetic anti-rheumatic drugs by increasing drug efflux. Future perspectives regarding pharmacologic NRF2 activation in RA are finally proposed.
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http://dx.doi.org/10.1016/j.freeradbiomed.2022.08.012 | DOI Listing |
Phytomedicine
December 2024
Department of Neurology, Fujian Medical University Union Hospital, Fuzhou, China; Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, China; Institute of Clinical Neurology, Fujian Medical University, Fuzhou, China. Electronic address:
Background: Perilladehyde, an extract of perillae in the Labiatae family, can produce significant anti-inflammatory and antioxidant effects. Although literature evidences the favorable effect of perillaldehyde on ischemic stroke, the exact mechanism remains blurred.
Purpose: This study attempted to explore the impact of perillaldehyde on cerebral ischemia-reperfusion injury and the related action mechanism.
Front Pharmacol
December 2024
Department of Convergence Medical Science, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.
Background: Huntington disease (HD), a neurodegenerative autosomal dominant disorder, is characterized by involuntary choreatic movements with cognitive and behavioral disturbances. Up to now, no therapeutic strategies are available to completely ameliorate the progression of HD. has various pharmacologic effects such as antioxidant and anti-inflammatory activities.
View Article and Find Full Text PDFFront Immunol
January 2025
Centro Multidisciplinario de Estudios en Biotecnología, Facultad de Medicina Veterinaria y Zootecnia, Universidad Michoacana de San Nicolás de Hidalgo, Morelia, Mexico.
Pathogenic bacteria trigger complex molecular interactions in hosts that are characterized mainly by an increase in reactive oxygen species (ROS) as well as an inflammation-associated response. To counteract oxidative damage, cells respond through protective mechanisms to promote resistance and avoid tissue damage and infection; among these cellular mechanisms the activation or inhibition of the nuclear factor E2-related factor 2 (Nrf2) is frequently observed. The transcription factor Nrf2 is considered the regulator of several hundred cytoprotective and antioxidant genes.
View Article and Find Full Text PDFArch Esp Urol
December 2024
Pediatric Surgery, Qilu Hospital of Shandong University, 250012 Jinan, Shandong, China.
Background: Doxorubicin (DOX) is a widely used anticancer drug; However, its nephrotoxicity limits its therapeutic efficacy. This study investigates the protective effects of Perilla Alcohol (PA) against DOX-induced nephrotic syndrome (NS), focusing on its antioxidant and anti-inflammatory properties through the nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways.
Methods: A DOX-induced nephrotic syndrome (NS) rat model and a DOX-treated Mouse Podocyte Cell line 5 (MPC5) cell model were used to evaluate the renal protective effects of PA.
Commun Biol
January 2025
Georgia Cancer Center, Augusta University, Augusta, GA, 30912, USA.
The transsulfuration (TSS) pathway is an alternative source of cysteine for glutathione synthesis. Little of the TSS pathway in antioxidant capacity in sickle cell disease (SCD) is known. Here, we evaluate the effects of TSS pathway activation through cystathionine beta-synthase (CBS) to attenuate reactive oxygen species (ROS) and ferroptosis stresses in SCD.
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