bims-mistre 2025-02-09 papers

bims-mistre

Biomed News

on Mito stress

Issue of 2025–02–09
twenty-six papers selected by
Ellen Siobhan Mitchell, MitoQ

Oxidative stress and reactive oxygen species in otorhinolaryngological diseases: insights from pathophysiology to targeted antioxidant therapies.
Mitochondrial Peroxiredoxins and Monoamine Oxidase-A: Dynamic Regulators of ROS Signaling in Cardioprotection.
Skeletal Muscle Innervation: Reactive Oxygen Species as Regulators of Neuromuscular Junction Dynamics and Motor Unit Remodeling.
Therapeutic modulation of mitochondrial dynamics by agmatine in neurodegenerative disorders.
Green coffee bean extract rich in chlorogenic acids prevents muscle capillary regression via inhibiting oxidative stress and enhancing angiogenesis.
Epigallocatechin-Gallate: Unraveling Its Protective Mechanisms and Therapeutic Potential.
The Role and Molecular Pathways of SIRT6 in Senescence and Age-related Diseases.
Therapeutic targeting of obesity-induced neuroinflammation and neurodegeneration.
Impaired Mitochondrial Function and Ubiquitin Proteasome System Activate α-Synuclein Aggregation in Zinc-Induced Neurotoxicity: Effect of Antioxidants.
Hyaluronic acid-curcumin nanoparticles for preventing the progression of experimental autoimmune uveitis through the Keap1/Nrf2/HO-1 signaling pathway.
Phytochemicals Targeting Mitophagy to Treat Heart Diseases: Retrospective Insights and Prospective Directions.
Investigating the Interplay Between the Nrf2/Keap1/HO-1/SIRT-1 Pathway and the p75NTR/PI3K/Akt/MAPK Cascade in Neurological Disorders: Mechanistic Insights and Therapeutic Innovations.
Baicalein protects against heart failure by improving mitochondrial dysfunction and regulating endoplasmic reticulum stress to reduce apoptosis in vitro and in vivo.
Improvements in Exercise for Alzheimer's Disease: Highlighting FGF21-Induced Cerebrovascular Protection.
Peroxisome proliferator-activated receptors (PPARs) agonists as promising neurotherapeutics.
Harnessing the fundamental roles of vitamins: the potent anti-oxidants in longevity.
Curcumin Suppresses ROS Production and Increases Mitochondrial Activity in Cumulus Cells and Oocytes of COCs Derived From Non-Vascularized Follicles in Pigs.
Diurnal variation in skeletal muscle mitochondrial function dictates time-of-day-dependent exercise capacity.
Estrogen-dependent activation of TRX2 reverses oxidative stress and metabolic dysfunction associated with steatotic disease.
Effects of GLP-1 Receptor Agonists in Alcohol Use Disorder.
Ceramides and Skin Health: New Insights.
Exploring glycolytic enzymes in disease: potential biomarkers and therapeutic targets in neurodegeneration, cancer and parasitic infections.
The Roles of Functional Bacterial Amyloids in Neurological Physiology and Pathophysiology: Pros and Cons for Neurodegeneration.
When short-chain fatty acids meet type 2 diabetes mellitus: Revealing mechanisms, envisioning therapies.
Modulatory effects of cinnamomi cortex and its components epicatechin and linalool on skin circadian rhythms.
Grape Seed Extract Pretreatment Prevents Mitochondrial Dysfunction and NLRP3 Inflammasome-Induced Inflammatory Response in Glial Cells Exposed to Paroxetine and Quinolinic Acid.

Redox Rep. 2025 Dec;30(1): 2458942

Oxidative stress and reactive oxygen species in otorhinolaryngological diseases: insights from pathophysiology to targeted antioxidant therapies.

Linghui Meng, Shengyang Liu, Jinfeng Luo, Yanyi Tu, Tao Li, Ping Li, Jinzhuang Yu, Li Shi.

  Oxidative stress, characterized by an imbalance between excessive reactive oxygen species (ROS) production and impaired antioxidant defenses, is closely linked to the pathogenesis of various otorhinolaryngological disorders. Mitochondria, as the primary site of cellular energy production, play a crucial role in modulating oxidative stress. Mitochondrial dysfunction exacerbates ROS generation, leading to cellular damage and inflammatory responses. In otorhinolaryngological diseases, oxidative stress is strongly associated with conditions such as hearing loss, allergic rhinitis, and chronic sinusitis, where oxidative damage and tissue inflammation are key pathological features. Recent studies have highlighted the potential of antioxidant therapies to mitigate oxidative stress and restore homeostasis, offering promising avenues for alleviating symptoms in these diseases. However, despite the encouraging results from early-stage research, the clinical efficacy of antioxidant interventions remains to be fully established. This review provides an overview of the role of oxidative stress in otorhinolaryngological diseases and evaluates the therapeutic potential of antioxidant strategies.

Keywords:  Mitochondrial dysfunction; allergic rhinitis; chronic rhinosinusitis; hearing loss; inflammation

DOI:  https://doi.org/10.1080/13510002.2025.2458942
Physiol Res. 2024 Dec 31. 73(6): 887-900

Mitochondrial Peroxiredoxins and Monoamine Oxidase-A: Dynamic Regulators of ROS Signaling in Cardioprotection.

M Ferko, P Alanova, D Janko, B Opletalova, N Andelova.

An excessive increase in reactive oxygen species (ROS) levels is one of the main causes of mitochondrial dysfunction. However, when ROS levels are maintained in balance with antioxidant mechanisms, ROS fulfill the role of signaling molecules and modulate various physiological processes. Recent advances in mitochondrial bioenergetics research have revealed a significant interplay between mitochondrial peroxiredoxins (PRDXs) and monoamine oxidase-A (MAO-A) in regulating ROS levels. Both proteins are associated with hydrogen peroxide (H2O2), MAO-A as a producer and PRDXs as the primary antioxidant scavengers of H2O2. This review focuses on the currently available knowledge on the function of these proteins and their interaction, highlighting their importance in regulating oxidative damage, apoptosis, and metabolic adaptation in the heart. PRDXs not only scavenge excess H2O2, but also act as regulatory proteins, play an active role in redox signaling, and maintain mitochondrial membrane integrity. Overexpression of MAO-A is associated with increased oxidative damage, leading to mitochondrial dysfunction and subsequent progression of cardiovascular diseases (CVD), including ischemia/reperfusion injury and heart failure. Considering the central role of oxidative damage in the pathogenesis of many CVD, targeting PRDXs activation and MAO-A inhibition may offer new therapeutic strategies aimed at improving cardiac function under conditions of pathological load related to oxidative damage. Keywords: Mitochondria, Peroxiredoxin, Monoamine oxidase-A, Reactive oxygen species, Cardioprotective signaling.
Free Radic Biol Med. 2025 Jan 30. pii: S0891-5849(25)00072-3. [Epub ahead of print]

Skeletal Muscle Innervation: Reactive Oxygen Species as Regulators of Neuromuscular Junction Dynamics and Motor Unit Remodeling.

Steve D Guzman, Susan V Brooks.

  This review explores the intricate processes of motor unit remodeling with a specific focus on the influence of reactive oxygen species (ROS) and oxidative stress on the primary cellular components: nerves/axons, muscle fibers, and muscle-resident glial cells. Emphasizing the role of redox biology, we highlight how oxidative stress impacts motor unit adaptation, injury response, and aging. By synthesizing findings from recent studies with seminal works, including investigations of myelin and terminal Schwann cells and neuromuscular junction (NMJ) dynamics, this review provides a comprehensive understanding of the molecular mechanisms underpinning motor unit maintenance and repair. The goal is to elucidate how oxidative stress influences these processes and to explore potential therapeutic strategies for neuromuscular disorders.

Keywords:  Denervation; Oxidative Stress; Reinnervation; Sarcopenia; Schwann Cell

DOI:  https://doi.org/10.1016/j.freeradbiomed.2025.01.053
Neuroscience. 2025 Jan 29. pii: S0306-4522(25)00077-6. [Epub ahead of print]569 43-57

Therapeutic modulation of mitochondrial dynamics by agmatine in neurodegenerative disorders.

Dhanshree Nibrad, Amit Shiwal, Manasi Tadas, Raj Katariya, Mayur Kale, Nandkishor Kotagale, Milind Umekar, Brijesh Taksande.

  Mitochondrial dysfunction is a pivotal factor in the pathogenesis of neurodegenerative disorders, driving neuronal degeneration through mechanisms involving oxidative stress, impaired energy production, and dysregulated calcium homeostasis. Agmatine, an endogenous polyamine derived from arginine, has garnered attention for its neuroprotective properties, including anti-inflammatory, anti-oxidative, and antiapoptotic effects. Recent studies have highlighted the potential of agmatine in preserving mitochondrial function and mitigating neurodegeneration, making it a promising candidate for therapeutic intervention. One of the key mechanisms by which agmatine exerts its neuroprotective effects is through the maintenance of mitochondrial homeostasis. Agmatine has been shown to modulate mitochondrial dynamics, promoting mitochondrial fusion and fission balance essential for cellular energy metabolism and signaling. Moreover, agmatine acts as a regulator of mitochondrial permeability transition pore (mPTP) opening, preventing excessive calcium influx and subsequent mitochondrial dysfunction. Despite promising findings, challenges such as optimizing agmatine's pharmacokinetics, determining optimal dosing regimens, and elucidating its precise molecular targets within mitochondria remain to be addressed. Future research directions should focus on developing targeted delivery systems for agmatine, investigating its interactions with mitochondrial proteins, and conducting well-designed clinical trials to evaluate its therapeutic efficacy and safety profile in neurodegenerative disorders. Overall, agmatine emerges as a novel therapeutic agent with the potential to modulate mitochondrial homeostasis and alleviate neurodegenerative pathology, offering new avenues for treating these debilitating conditions.

Keywords:  Agmatine; Calcium Homeostasis; Mitochondrial Dynamics; Mitochondrial Homeostasis; Neurodegenerative Disorders; Oxidative Stress

DOI:  https://doi.org/10.1016/j.neuroscience.2025.01.061
Biomed Res. 2025 ;46(1): 15-25

Green coffee bean extract rich in chlorogenic acids prevents muscle capillary regression via inhibiting oxidative stress and enhancing angiogenesis.

Jihao Xing, Hao Lin, Ryosuke Nakanishi, Kazuya Iwai, Noriaki Maeshige, Hiroyo Kondo, Hidemi Fujino.

Reactive oxygen species (ROS) production in disused skeletal muscle induces capillary regression, which disrupts the balance of pro- and anti-angiogenic factors. We tested whether green coffee bean extract containing rich chlorogenic acid, which has antioxidant properties, can prevent capillary regression caused by muscle atrophy. The study included 24 female Sprague-Dawley rats, randomly assigned to four groups: control (CON), 2-week hindlimb unloading (HU), 2-week hindlimb unloading supplemented with coffee extract rich in chlorogenic acids (HU+50%CGA), and 2-week hindlimb unloading supplemented with trace amounts of chlorogenic acids (HU+5%CGA). Rats in the HU+50%CGA and HU+5%CGA groups received an oral dose of coffee extract at 850 mg/kg per day. The effects of chlorogenic acids in coffee extracts were investigated by comparing these groups. Unloading increased oxidative stress, disrupted mitochondrial oxidative activity, and upregulated TSP-1 expression, triggering endothelial cell apoptosis and leading to capillary regression. In contrast, the supplementation with coffee extract containing rich chlorogenic acids prevented ROS overproduction and improved metabolic activity, promoting angiogenesis by correcting the imbalance of pro- and anti-angiogenic factors, and inhibiting endothelial cell apoptosis. In conclusion, green coffee bean extract rich in chlorogenic acids inhibits ROS production, enhances mitochondrial metabolism, mitigates capillary regression by promoting angiogenesis and preventing apoptosis.

DOI: https://doi.org/10.2220/biomedres.46.15
Cell Biochem Funct. 2025 Feb;43(2): e70056

Epigallocatechin-Gallate: Unraveling Its Protective Mechanisms and Therapeutic Potential.

Xiang-Wen Dong, Wen-Lan Fang, Yun-Hang Li, Yu-Rong Chai.

  Epigallocatechin-gallate (EGCG), the predominant catechin in green tea, is a key constituent of tea polyphenols. Due to the EGCG's diverse biological activities of anti-inflammatory, antioxidant, and so forth, green tea is believed to exert a positive influence on a variety of diseases. And extensive research had uncovered a range of protective effects attributed to EGCG, indicating its potential to mitigate various pathological conditions. The precise mechanisms through which EGCG operates remain a subject of ongoing discussion among researchers. Reactive oxygen species (ROS), a primary culprit in oxidative stress, have been demonstrated to be reduced by EGCG. Furthermore, nuclear factor kappa-B (NF-κB), a pivotal signal molecular of inflammation progress, has been observed to be suppressed by EGCG. Sirtuins1 (Sirt1) is a histone deacetylase, the obligate substrate of which is NAD+. Evidence suggests that EGCG can enhance the activities of Sirt1 to induce autophagy to protect inflammation injury and oxidative stress in tissues and organs. Despite the promising protective effects of EGCG, its clinical use is constrained by its limited bioavailability. This review aims to consolidate the existing evidence and elucidate the mechanisms that support EGCG's protective role, as well as to explore the challenges and potential strategies for its clinical application.

Keywords:  EGCG; Sirt1; antioxidant; anti‐inflammation; autophagy

DOI:  https://doi.org/10.1002/cbf.70056
Adv Biol (Weinh). 2025 Feb 06. e2400469

The Role and Molecular Pathways of SIRT6 in Senescence and Age-related Diseases.

Yi Lu, Junye Yang, Qiuju Wu, Xiaobo Wang.

  SIRT6 is a NAD+-dependent histone deacetylase with crucial roles in controlling DNA damage repair, telomere homeostasis, oxidative stress, autophagy, and other cellular processes, and it has long been recognized as a longevity-associated protein. This review details its anti-aging-related mechanisms. First, SIRT6 facilitates DNA repair pathways and maintains genome stability by deacetylating histone H3 at K56, K9, and K18 residues, in addition to participating in DNA damage repair through mono-ADP-ribosylation and other mechanisms. Second, SIRT6 preserves telomere integrity and mitigates cellular senescence by reducing oxidative stress-induced damage through the regulation of reactive oxygen species (ROS), inhibition of inflammation, and other pathways. Furthermore, SIRT6 promotes autophagy, slowing cellular senescence via the modulation of various signaling pathways, including AMPK, IGF-Akt-mTOR, H133Y, IL-1β, and mitochondrial autophagy-related proteins. Finally, SIRT6 regulates multiple signaling pathways, such asNF-κB, FOXO, and AMPK, to counteract the aging process. This review particularly delves into the interplay between SIRT6 and various diseases, including tumors, cardiovascular diseases (e.g., atherosclerosis, heart failure), metabolic diseases (e.g., type 2 diabetes, dyslipidemia, gluconeogenesis, osteoporosis), and neurodegenerative diseases (e.g., Alzheimer's disease). Moreover, recent advancements in SIRT6-regulated compounds (e.g., C3G, BZBS, Fisetin, FNDC5, Lycorine hydrochloride, and Ergothioneine) are discussed as potential therapeutic agents for these mediated diseases.

Keywords:  SIRT6; mechanisms of senescence; senescence; senescence‐related diseases; signaling pathway

DOI:  https://doi.org/10.1002/adbi.202400469
Front Endocrinol (Lausanne). 2024 ;15 1456948

Therapeutic targeting of obesity-induced neuroinflammation and neurodegeneration.

Jialiu Zeng, Lenny Yi Tong Cheong, Chih Hung Lo.

  Obesity is a major modifiable risk factor leading to neuroinflammation and neurodegeneration. Excessive fat storage in obesity promotes the progressive infiltration of immune cells into adipose tissue, resulting in the release of pro-inflammatory factors such as cytokines and adipokines. These inflammatory mediators circulate through the bloodstream, propagating inflammation both in the periphery and in the central nervous system. Gut dysbiosis, which results in a leaky intestinal barrier, exacerbates inflammation and plays a significant role in linking obesity to the pathogenesis of neuroinflammation and neurodegeneration through the gut-brain/gut-brain-liver axis. Inflammatory states within the brain can lead to insulin resistance, mitochondrial dysfunction, autolysosomal dysfunction, and increased oxidative stress. These disruptions impair normal neuronal function and subsequently lead to cognitive decline and motor deficits, similar to the pathologies observed in major neurodegenerative diseases, including Alzheimer's disease, multiple sclerosis, and Parkinson's disease. Understanding the underlying disease mechanisms is crucial for developing therapeutic strategies to address defects in these inflammatory and metabolic pathways. In this review, we summarize and provide insights into different therapeutic strategies, including methods to alter gut dysbiosis, lifestyle changes, dietary supplementation, as well as pharmacological agents derived from natural sources, that target obesity-induced neuroinflammation and neurodegeneration.

Keywords:  body-brain interactions; metabolic dysfunction; neurodegeneration; neuroinflammation; obesity; therapeutic targeting

DOI:  https://doi.org/10.3389/fendo.2024.1456948
J Mol Neurosci. 2025 Feb 05. 75(1): 16

Impaired Mitochondrial Function and Ubiquitin Proteasome System Activate α-Synuclein Aggregation in Zinc-Induced Neurotoxicity: Effect of Antioxidants.

Garima Singh, Namrata Mittra, Chetna Singh.

  Impairment in mitochondrial function and ubiquitin-proteasome system (UPS) and alpha-synuclein (α-Syn) aggregation are implicated in Zn-induced neurotoxicity. A link among these events leading to Zn-induced neurotoxicity is not yet properly deciphered. Therefore, the study intended to check the existence of a crosstalk between the mitochondria and UPS and its further link to α-Syn aggregation. The study also aimed to investigate the efficacy of tempol, a SOD mimetic and silymarin, a natural antioxidant, against Zn-induced alterations in animals and differentiated cells. Zn reduced the locomotor activity, dopamine content and tyrosine hydroxylase (TH) expression in the exposed animals. Zn augmented the levels of mitochondrial reactive oxygen species, α-Syn and protein-ubiquitin conjugates. Mitochondrial membrane potential, adenosine triphosphate (ATP) production, UPS-associated enzymatic activities and levels of UPS subunits (SUG-1 and β-5) were attenuated in Zn-exposed animals. While Zn augmented the expression of heat shock protein 110 (HSP110), peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α) and Parkin translocation, the mitochondrial PTEN-induced kinase-1 (PINK-1) level was attenuated. In addition to tempol and silymarin, a mitochondrial permeability transition pore inhibitor, cyclosporine A, also alleviated the Zn-induced changes in animals. Similar trends in a few parameters were also observed in the differentiated human neuroblastoma SH-SY-5Y cells. Besides, UPS inhibitor, MG132, enhanced Zn-induced UPS impairment, protein aggregation and mitochondrial dysfunction in differentiated cells. These results suggest that mitochondrial dysfunction triggers UPS impairment or vice versa that elevates α-Syn aggregation and consequent neuronal death. Furthermore, tempol and silymarin ameliorate the mitochondrial and UPS impairments and α-Syn aggregation thereby providing protection from Zn-induced neurotoxicity.

Keywords:  Antioxidant; Dopaminergic neurodegeneration; Mitochondrial dysfunction; Ubiquitin proteasome system; Zinc; α-synuclein aggregation

DOI:  https://doi.org/10.1007/s12031-024-02293-5
J Nanobiotechnology. 2025 Feb 07. 23(1): 89

Hyaluronic acid-curcumin nanoparticles for preventing the progression of experimental autoimmune uveitis through the Keap1/Nrf2/HO-1 signaling pathway.

Weiwei Tang, Xiaomin Huang, Yun-Di Yi, Fan Cao, Manli Deng, Jiawei Fan, Zheng-Xuan Jiang, Li-Ming Tao, Xianwen Wang, Lei Shi.

  Globally, uveitis is a collection of intraocular inflammatory disorders that affect mainly the uvea, resulting in irreversible blindness and a heavy socioeconomic burden. Excessive autoimmune inflammation and oxidative stress are major drivers that contribute to the initiation and progression of uveitis. Nevertheless, current therapeutic methods for uveitis are limited and are accompanied by several serious adverse effects. Recently, nanotechnology-based antioxidant strategies have provided novel options for the treatment of ocular diseases. Although curcumin (CUR) has prominent antioxidant capacity and reactive oxygen species (ROS) scavenging ability, its low bioavailability and undetermined mechanisms limit its extensive application. This investigation demonstrated that esterified hyaluronic acid-curcumin nanoparticles (HA-CUR NPs) with superior aqueous dispersion exhibited exceptional antioxidant enzyme mimetic activity, incorporating superoxide dismutase (SOD), glutathione (GSH), catalase (CAT), and free radical scavenging ability. Further in vitro and in vivo experimental results validated the protective function of HA-CUR NPs against oxidative stress-induced damage and inflammatory responses, attenuated pathological progression, relieved microvascular damage, and regulated fundus blood flow in retinal vascular networks. This may be attributable to the specific ability of HA-CUR NPs to target the CD44 receptor and activate the Keap1/Nrf2/HO-1 signaling pathway, suggesting a potential mechanism. In summary, this study revealed that HA-CUR NPs, which are composed of a natural product and biomacromolecules with outstanding artificial antioxidant enzyme activities, may be novel agents for effectively and safely treating uveitis and other ROS-related diseases.

Keywords:  Curcumin; Experimental autoimmune uveitis; Hyaluronic acid; Nanoparticles; Oxidative stress

DOI:  https://doi.org/10.1186/s12951-024-03082-3
Phytother Res. 2025 Feb 06.

Phytochemicals Targeting Mitophagy to Treat Heart Diseases: Retrospective Insights and Prospective Directions.

Qin Dong, Yichan Zhu, Xinghai Zhang, Lu Li, Yi Yang, Chuan Liu, Jianxia Wen.

  Mitophagy is a process by which cells selectively eliminate damaged or dysfunctional mitochondria through the autophagy-lysosome pathway, thereby maintaining mitochondrial quality and cellular homeostasis. This process is closely linked to the onset and progression of various heart diseases. Modern pharmacological research has demonstrated that phytochemicals can regulate mitochondrial homeostasis in cardiomyocytes through multiple mechanisms, influencing mitophagy and protecting cardiomyocytes, which in turn exerts anti-cardiovascular effects. However, the underlying mechanisms of these effects are not yet fully understood. This study summarizes the pharmacological effects and molecular mechanisms of mitophagy in heart diseases, aiming to provide reference for the research and treatment of phytochemicals targeting mitophagy against heart diseases. The results indicated that phytochemicals (such as Berberine, Ginsenoside Rg1, Quercetin, Resveratrol, Baicalein, and so on) can exert preventive and therapeutic effects on heart diseases (such as cardiac toxicity or damage, myocardial ischemia/reperfusion injury, heart failure, heart aging, cardiac hypertrophy, cardiomyopathy, and so on.) via regulating the PINK1/Parkin and FUNDC1-dependent mitophagy pathway. These compounds mainly exert their effects by regulating mitochondrial homeostasis, mitochondrial dynamics, mitochondrial oxidative stress, mitochondrial apoptosis, and mitochondrial energy metabolism. This study provides a reference that phytochemicals have effect on anti-cardiovascular effects by regulating mitophagy. However, further in-depth mechanistic and clinical research are needed in the future.

Keywords:  PINK1/Parkin; energy metabolism; heart diseases; mitophagy; phytochemicals

DOI:  https://doi.org/10.1002/ptr.8448
Mol Neurobiol. 2025 Feb 07.

Investigating the Interplay Between the Nrf2/Keap1/HO-1/SIRT-1 Pathway and the p75NTR/PI3K/Akt/MAPK Cascade in Neurological Disorders: Mechanistic Insights and Therapeutic Innovations.

Ritam Mukherjee, Ravi Rana, Sidharth Mehan, Zuber Khan, Ghanshyam Das Gupta, Acharan S Narula, Rajaram Samant.

  Neurological illnesses are debilitating diseases that affect brain function and balance. Due to their complicated aetiologies and progressive nature, neurodegenerative and neuropsychiatric illnesses are difficult to treat. These incurable conditions damage brain functions like mobility, cognition, and emotional regulation, but medication, gene therapy, and physical therapy can manage symptoms. Disruptions in cellular signalling pathways, especially those involving oxidative stress response, memory processing, and neurotransmitter modulation, contribute to these illnesses. This review stresses the interplay between key signalling pathways involved in neurological diseases, such as the Nrf2/Keap1/HO-1/SIRT-1 axis and the p75NTR/PI3K/Akt/MAPK cascade. To protect neurons from oxidative damage and death, the Nrf2 transcription factor promotes antioxidant enzyme production. The Keap1 protein releases Nrf2 during oxidative stress for nuclear translocation and gene activation. The review also discusses how neurotrophin signalling through the p75 neurotrophin receptor (p75NTR) determines cell destiny, whether pro-survival or apoptotic. The article highlights emerging treatment approaches targeting these signalling pathways by mapping these connections. Continued research into these molecular pathways may lead to new neurological disease treatments that restore cellular function and neuronal survival. In addition to enhanced delivery technologies, specific modulators and combination therapies should be developed to fine-tune signalling responses. Understanding these crosstalk dynamics is crucial to strengthening neurological illness treatment options and quality of life.

Keywords:  Akt; HO-1; Keap1; MAPKs; Neurodegeneration; Neurological disorders; Neuropsychiatric disorders; Nrf2; P75NTR; PI3K; SIRT-1 axis; Therapeutic strategies

DOI:  https://doi.org/10.1007/s12035-025-04725-8
Int J Immunopathol Pharmacol. 2025 Jan-Dec;39:39 3946320251315800

Baicalein protects against heart failure by improving mitochondrial dysfunction and regulating endoplasmic reticulum stress to reduce apoptosis in vitro and in vivo.

Zhao Zhang, Xuan Zhang, Yan Yang, HongYang Wang, Xiangjun Yang, Liying Xuan, Danli Yang, Guoyou Zhang, Yu Wang.

   OBJECTIVES: Baicalein, a flavonoid derived from the roots of Scutellaria baicalensis Georgi, demonstrates multifarious pharmacological effects due to its high antioxidant activity. However, the latent mechanisms remain insufficiently resolved. In the present research, we evaluated the therapeutic effects of baicalein on isoprenaline (ISO)-induced heart failure and investigated the possible underlying mechanisms.
METHODS: Toxicity was analyzed in zebrafish embryos and mouse atrial myocytes HL-1. The MTT assay was used to evaluate the effectiveness of baicalein. DCFH-DA was used as a fluorescence probe to detect intracellular reactive oxygen species (ROS). Superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) levels were measured using SOD, MDA and GSH-Px commercial kits. Adult BALB/c mice were randomized into six groups of ten animals each. Cardiac function was analyzed by echocardiographic images. Structural changes were analyzed by hematoxylin & eosin (HE) staining, Masson staining and TUNEL staining. The mechanism of baicalein was investigated by analyzing relative signaling pathways through western blotting.
RESULTS: Our studies show that baicalein both significantly reduces ISO-induced oxidative stress, apoptosis and cardiac fibrosis in vitro and vivo, this phenomenon was related to mitochondrial fusion/fission balance and inhibiting GRP78/CHOP pathway.
CONCLUSIONS: Our results suggested that baicalein controls mitochondrial fusion/fission balance and inhibits GRP78/CHOP pathway, thus exerting therapeutic effects in ISO-induced heart failure in HL-1 cells and BALB/c mice. These results suggested that baicalein may be a potential therapeutic agent for heart failure.

Keywords:  GRP78/CHOP pathway; baicalein; heart failure; mitochondrial fusion/fission balance

DOI:  https://doi.org/10.1177/03946320251315800
Neurochem Res. 2025 Feb 04. 50(2): 95

Improvements in Exercise for Alzheimer's Disease: Highlighting FGF21-Induced Cerebrovascular Protection.

Juan Wang, Xiangyuan Meng, Jialun Yang, Yingzhe Tang, Fanqi Zeng, Yiyang Wang, Zeyu Chen, Dandan Chen, Ruihan Zou, Wenfeng Liu.

  Alzheimer's disease (AD) is the most common neurodegenerative disease. Currently, it has shown a trend of earlier onset, with most patients experiencing a progressive decline in cognitive function following the disease's onset, which places a heavy burden on society and family. Since no drug cure for AD exists, exploring new ways for its treatment and prevention has become critical. Early vascular damage is an initial trigger for neuronal injury in AD, underscoring the importance of vascular health in the early stages of the disease. Patients with early AD experience abnormal blood-brain barrier transport of amyloid-β (Aβ) peptides, with excess Aβ being deposited in the cerebral vasculature. The toxic effects of Aβ lead to abnormalities in cerebrovascular structure and function. Fibroblast growth factor21 (FGF21) is an endocrine factor that positively regulates energy homeostasis and glucose-lipid metabolism. Notably, it is one of the effective targets for metabolic disease prevention and treatment. Recent studies have found that FGF21 has anti-aging and vasoprotective effects, with receptors for FGF21 present in the brain. Exercise stimulates the liver to produce large amounts of FGF21, which enters the blood-brain barrier with the blood to exert neurovascular protection. Therefore, we review the biological properties of FGF21, its role in the cerebrovascular structure and function in AD, and the mechanism of exercise-regulated FGF21 action on AD-related cerebrovascular changes, aiming to provide a new theoretical basis for using exercise to ameliorate degenerative neurological diseases.

Keywords:  Alzheimer's Disease; Cerebrovascular structure and function; Exercise; FGF21; Oxidative stress

DOI:  https://doi.org/10.1007/s11064-025-04350-w
Bioorg Chem. 2025 Jan 30. pii: S0045-2068(25)00106-3. [Epub ahead of print]156 108226

Peroxisome proliferator-activated receptors (PPARs) agonists as promising neurotherapeutics.

Iman A Y Ghannam, Rasha M Hassan, Mohammed S Abdel-Maksoud.

  Neurodegenerative disorders are characterized by a continuous neurons loss resulting in a wide range of pathogenesis affecting the motor impairment. Several strategies are outlined for therapeutics of synthetic and natural PPARs agonists in some neurological disorders; Parkinson's disease (PD), Alzheimer's disease (AD), Multiple sclerosis (MS), Amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD). The aim of this review is to provide a recent update of the previously reported studies, and reviews dealing with the medicinal chemistry of PPARs and their agonists, and to highlight the outstanding advances in the development of both synthetic compounds including; PPARα agonists (fibrates), PPARγ agonists (thiazolidindiones), and PPARβ/δ agonists either as sole or dual acting PPAR full or pan agonists, in addition to the natural phytochemicals; acids, cannabinoids, and flavonoids for their different neuroprotection effects in the previously mentioned neurodegenerative disorders (PD, AD, MS, ALS, and HD). Moreover, this review reports the diverse pre-clinical and clinical studies of PPARs agonists in the neurodegenerative diseases via cellular, and animal models and human.

Keywords:  Autophagy; Mitochondrial Biogenesis; Neurodegenerative Disorders; Neuroprotection; PPARs

DOI:  https://doi.org/10.1016/j.bioorg.2025.108226
Biogerontology. 2025 Feb 07. 26(2): 58

Harnessing the fundamental roles of vitamins: the potent anti-oxidants in longevity.

Mehran Izadi, Nariman Sadri, Amirhossein Abdi, Mohammad Mahdi Raeis Zadeh, Sana Sadatipour, Ghazalnaz Baghdadi, Dorsa Jalaei, Safa Tahmasebi.

  Aging is a complex and heterogeneous biological process characterized by telomere attrition, genomic instability, mitochondrial dysfunction, and disruption in nutrient sensing. Besides contributing to the progression of cancer, metabolic disorders, and neurodegenerative diseases, these manifestations of aging also adversely affect organ function. It is crucial to understand these mechanisms and identify interventions to modulate them to promote healthy aging and prevent age-related diseases. Vitamins have emerged as potential modulators of aging beyond their traditional roles in health maintenance. There is an increasing body of evidence that hormetic effects of vitamins are responsible for activating cellular stress responses, repair mechanisms, and homeostatic processes when mild stress is induced by certain vitamins. It is evident from this dual role that vitamins play a significant role in preventing frailty, promoting resilience, and mitigating age-related cellular damage. Moreover, addressing vitamin deficiencies in the elderly could have a significant impact on slowing aging and extending life expectancy. A review of recent advances in the role of vitamins in delaying aging processes and promoting multiorgan health is presented in this article. The purpose of this paper is to provide a comprehensive framework for using vitamins as strategic tools for fostering longevity and vitality. It offers a fresh perspective on vitamins' role in aging research by bridging biological mechanisms and clinical opportunities.

Keywords:  Aging; Epigenetic; Immune system; Longevity; Oxidative stress; Vitamin

DOI:  https://doi.org/10.1007/s10522-025-10202-5
Anim Sci J. 2025 Jan-Dec;96(1):96(1): e70032

Curcumin Suppresses ROS Production and Increases Mitochondrial Activity in Cumulus Cells and Oocytes of COCs Derived From Non-Vascularized Follicles in Pigs.

Tomoya Nakanishi, Shingo Tonai, Haruto Ichikawa, Shota Mori, Shinji Ishihara, Yongjin Chang, Yasuhisa Yamashita.

  In vitro maturation (IVM) produces offspring from domestic animals; however, the blastocyst rate after IVM was low. We previously reported that the developmental competence of oocytes derived from follicles with blood vessels absent on the surface (non-vascularized follicles: NVF) is quite low compared to those derived from follicles with blood vessels present on the surface (vascularized follicles: VF). Thus, it is important to develop technique to improve the quality of NVF-derived oocyte by IVM. Since it has been reported that reactive oxygen species (ROS) reduces oocyte quality, in this study, we investigated whether curcumin that is known as antioxidant could improve oocyte quality derived from NVF. As results, cultivation of NVF Cumulus-oocyte complexes (COCs) with curcumin significantly improved cumulus expansion and oocyte meiotic maturation of NVF COCs compared to those of NVF COCs without curcumin. Cultivation with curcumin of NVF COCs significantly improved the proliferative activity of cumulus cells. Furthermore, the cultivation significantly reduced ROS activity and increased mitochondrial activity. Hence, it was revealed that the addition of curcumin to the maturation medium increased mitochondrial activity and reduced ROS levels in NVF-derived cumulus cells and oocytes, thereby improving the maturation of oocytes within COCs.

Keywords:  ROS; cumulus cells; in vitro maturation (IVM); oocyte; pig

DOI:  https://doi.org/10.1111/asj.70032
FASEB J. 2025 Feb 15. 39(3): e70365

Diurnal variation in skeletal muscle mitochondrial function dictates time-of-day-dependent exercise capacity.

Subhash Khatri, Souparno Das, Anshit Singh, Shabbir Ahmad, Mohit Kashiv, Sunil Laxman, Ullas Kolthur-Seetharam.

  Exercise impinges on almost all physiological processes at an organismal level and is a potent intervention to treat various diseases. Exercise performance is well established to display diurnal rhythm, peaking during the late active phase. However, the underlying molecular/metabolic factors and mitochondrial energetics that possibly dictate time-of-day exercise capacity remain unknown. Here, we have unraveled the importance of diurnal variation in mitochondrial functions as a determinant of skeletal muscle exercise performance. Our results show that exercise-induced muscle metabolome and mitochondrial energetics are distinct at ZT3 and ZT15. Importantly, we have elucidated key diurnal differences in mitochondrial functions that are well correlated with disparate time-of-day-dependent exercise capacity. Providing causal mechanistic evidence, we illustrate that loss of Sirtuin4 (SIRT4), a well-known mitochondrial regulator, abrogates mitochondrial diurnal variation and consequently abolishes time-of-day-dependent muscle output. Therefore, our findings unequivocally demonstrate the pivotal role of baseline skeletal muscle mitochondrial functions in dictating diurnal exercise capacity.

Keywords:  Sirtuin4 (SIRT4); chronobiology; circadian exercise physiology; exercise metabolism; mitochondrial metabolism; skeletal muscle energetics; time‐of‐day exercise capacity

DOI:  https://doi.org/10.1096/fj.202402930R
Cell Death Dis. 2025 Jan 31. 16(1): 57

Estrogen-dependent activation of TRX2 reverses oxidative stress and metabolic dysfunction associated with steatotic disease.

Alfredo Smiriglia, Nicla Lorito, Marina Bacci, Angela Subbiani, Francesca Bonechi, Giuseppina Comito, Marta Anna Kowalik, Andrea Perra, Andrea Morandi.

Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses a spectrum of hepatic disorders, ranging from simple steatosis to steatohepatitis, with the most severe outcomes including cirrhosis, liver failure, and hepatocellular carcinoma. Notably, MASLD prevalence is lower in premenopausal women than in men, suggesting a potential protective role of estrogens in mitigating disease onset and progression. In this study, we utilized preclinical in vitro models-immortalized cell lines and hepatocyte-like cells derived from human embryonic stem cells-exposed to clinically relevant steatotic-inducing agents. These exposures led to lipid droplet (LD) accumulation, increased reactive oxygen species (ROS) levels, and mitochondrial dysfunction, along with decreased expression of markers associated with hepatocyte functionality and differentiation. Estrogen treatment in steatotic-induced liver cells resulted in reduced ROS levels and LD content while preserving mitochondrial integrity, mediated by the upregulation of mitochondrial thioredoxin 2 (TRX2), an antioxidant system regulated by the estrogen receptor. Furthermore, disruption of TRX2, either pharmacologically using auranofin or through genetic interference, was sufficient to counteract the protective effects of estrogens, highlighting a potential mechanism through which estrogens may prevent or slow MASLD progression.

DOI: https://doi.org/10.1038/s41419-025-07331-7
Basic Clin Pharmacol Toxicol. 2025 Mar;136(3): e70004

Effects of GLP-1 Receptor Agonists in Alcohol Use Disorder.

Mette Kruse Klausen, Gitte Moos Knudsen, Tina Vilsbøll, Anders Fink-Jensen.

  In the search for novel treatment strategies for alcohol use disorder (AUD), glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) approved for treating Type 2 diabetes and obesity have caught much attention. GLP-1 is a naturally occurring peptide produced in the small intestines and the brain, regulating plasma glucose levels and satiety. This focused review will report on the preclinical studies, case stories, register-based cohort studies, brain-imaging data and secondary analysis of clinical data supporting the role of GLP-1RAs as a novel treatment of AUD. Several clinical trials are ongoing, examining the potential effects of the GLP-1RA semaglutide in AUD.

Keywords:  AUD; GLP‐1; alcohol use disorder; fMRI; glucagon‐like peptide‐1

DOI:  https://doi.org/10.1111/bcpt.70004
Exp Dermatol. 2025 Feb;34(2): e70042

Ceramides and Skin Health: New Insights.

Tze Lek Yong, Rahela Zaman, Navedur Rehman, Chung Keat Tan.

  Ceramide has transitioned from an incidental discovery to a vital element in skincare, becoming a thoroughly studied compound in the quest to treat skin conditions. Creating a moisture barrier, preserving hydration, regulating pH, controlling inflammation, and enhancing skin functions and appearance are among its established benefits. It is often used medically to repair skin barrier defects, as observed in inflammatory skin conditions like atopic dermatitis (AD) and dry skin types. Furthermore, ceramide and its metabolites are commonly used as predictors before disease manifestation and for prognostication processes, thus can be used as biomarker for clinical diagnosis as well. In the last couple of decades, momentum was also seen in the pre-clinical studies involving anti-cancer and nanotechnology field, whereby ceramide was also used as a drug, a carrier, or even adjunct formulation to increase efficacy of treatment such as chemotherapy. Approaches to increase ceramide levels include directly replenishing lost ceramides with natural extracts, synthetic pseudo-ceramides, or ceramide-like analogues, as well as using supplements that stimulate the body's natural ceramide production. Although ceramide is a well-known treatment in skincare and for common skin conditions like AD and psoriasis, its development and related pharmacology for severe skin conditions, such as skin cancer, remain in pre-clinical stages. Hence, the purpose of this research is to explore the role of ceramide in skin health and its application in common skin diseases.

Keywords:  anti‐inflammatory; ceramide; skin barrier function; skin disease; skin hydration

DOI:  https://doi.org/10.1111/exd.70042
Open Biol. 2025 Feb;15(2): 240239

Exploring glycolytic enzymes in disease: potential biomarkers and therapeutic targets in neurodegeneration, cancer and parasitic infections.

Maura Rojas-Pirela, Diego Andrade-Alviárez, Verónica Rojas, Miguel Marcos, Daniel Salete-Granado, Marirene Chacón-Arnaude, María Á Pérez-Nieto, Ulrike Kemmerling, Juan Luis Concepción, Paul A M Michels, Wilfredo Quiñones.

  Glycolysis, present in most organisms, is evolutionarily one of the oldest metabolic pathways. It has great relevance at a physiological level because it is responsible for generating ATP in the cell through the conversion of glucose into pyruvate and reducing nicotinamide adenine dinucleotide (NADH) (that may be fed into the electron chain in the mitochondria to produce additional ATP by oxidative phosphorylation), as well as for producing intermediates that can serve as substrates for other metabolic processes. Glycolysis takes place through 10 consecutive chemical reactions, each of which is catalysed by a specific enzyme. Although energy transduction by glucose metabolism is the main function of this pathway, involvement in virulence, growth, pathogen-host interactions, immunomodulation and adaptation to environmental conditions are other functions attributed to this metabolic pathway. In humans, where glycolysis occurs mainly in the cytosol, the mislocalization of some glycolytic enzymes in various other subcellular locations, as well as alterations in their expression and regulation, has been associated with the development and progression of various diseases. In this review, we describe the role of glycolytic enzymes in the pathogenesis of diseases of clinical interest. In addition, the potential role of these enzymes as targets for drug development and their potential for use as diagnostic and prognostic markers of some pathologies are also discussed.

Keywords:  diagnostic; glycolysis; pathogenesis of diseases; prognostic; therapeutic

DOI:  https://doi.org/10.1098/rsob.240239
Microb Pathog. 2025 Feb 03. pii: S0882-4010(25)00088-9. [Epub ahead of print] 107363

The Roles of Functional Bacterial Amyloids in Neurological Physiology and Pathophysiology: Pros and Cons for Neurodegeneration.

Hossein Halimi, Behrooz Ahmadi, Nastaran Asri, Mohammad Rostami-Nejad, Hamidreza Houri.

  Bacterial biofilms, which are complex communities of microorganisms encapsulated in a self-produced extracellular matrix, play critical roles in various diseases. Recent research has underscored the dualistic nature of amyloids, structural proteins within these biofilms, in human health, particularly highlighting the significant role in neurodegenerative disorders such as Alzheimer's (AD) and Parkinson's disease (PD). These amyloids modulate the immune response by inducing the production of interleukin-10 (IL-10), which plays a role in anti-inflammatory processes. Additionally, they inhibit the aggregation of human amyloids and enhance the integrity of the intestinal barrier. Detrimentally, they exacerbate neuroinflammation by elevating inflammatory cytokines and promoting the aggregation of human amyloid proteins-amyloid-β (Aβ) in AD and α-synuclein (αS) in PD-through a process known as cross-seeding. Moreover, bacterial amyloids have also been shown to stimulate the production of anti-curli/DNA antibodies, which are implicated in the pathogenesis of autoimmune diseases. Given their dualistic nature, bacterial amyloids may, under specific conditions, function as beneficial proteins for human health. This understanding holds promise for the development of targeted therapeutic strategies aimed at modulating bacterial amyloids in the context of neurodegenerative diseases, such as AD and PD.

Keywords:  Alzheimer’s disease; Amyloid-β; Bacterial amyloid; Biofilm; Neurodegeneration; Parkinson’s disease

DOI:  https://doi.org/10.1016/j.micpath.2025.107363
Biochem Pharmacol. 2025 Jan 31. pii: S0006-2952(25)00053-X. [Epub ahead of print]233 116791

When short-chain fatty acids meet type 2 diabetes mellitus: Revealing mechanisms, envisioning therapies.

Cong Xie, Cong Qi, Jianwen Zhang, Wei Wang, Xing Meng, Aifeila Aikepaer, Yuhan Lin, Chang Su, Yunlu Liu, Xingzhong Feng, Huijuan Gao.

  Evidence is accumulating that short-chain fatty acids (SCFAs) produced by the gut microbiota play pivotal roles in host metabolism. They contribute to the metabolic regulation and energy homeostasis of the host not only by preserving intestinal health and serving as energy substrates but also by entering the systemic circulation as signaling molecules, affecting the gut-brain axis and neuroendocrine-immune network. This review critically summarizes the current knowledge regarding the effects of SCFAs in the fine-tuning of the pathogenesis of type 2 diabetes mellitus (T2DM) and insulin resistance, with an emphasis on the complex relationships among diet, microbiota-derived metabolites, T2DM inflammation, glucose metabolism, and the underlying mechanisms involved. We hold an optimistic view that elucidating how diet can influence gut bacterial composition and activity, SCFA production, and metabolic functions in the host will advance our understanding of the mutual interactions of the intestinal microbiota with other metabolically active organs, and may pave the way for harnessing these pathways to develop novel personalized therapeutics for glucometabolic disorders.

Keywords:  Glucose homeostasis; Gut microbiota; Insulin resistance; Short-chain fatty acids; Type 2 diabetes

DOI:  https://doi.org/10.1016/j.bcp.2025.116791
Sci Rep. 2025 Feb 06. 15(1): 4480

Modulatory effects of cinnamomi cortex and its components epicatechin and linalool on skin circadian rhythms.

Ji-Young Kim, Juyeon Lee, Soo-Hyeon Lee, Eui-Man Jung, Kyung-Ha Lee.

  Circadian rhythms, intrinsic 24-h cycles regulating physiological processes, are crucial for skin homeostasis. Disruptions in these rhythms are linked to various skin disorders and impaired barrier function. Circadian rhythms can be modulated by botanical compounds, which hold therapeutic potential. However, the effect of cinnamomi cortex (CC), an anti-inflammatory, antioxidant, and antimicrobial agent, on the circadian rhythm of keratinocytes remains unclear. This study aimed to examine the effects of CC extract and its 18 individual components on the circadian rhythm of HaCaT, an immortalized human keratinocyte line. CC extract and its bioactive components epicatechin (EC) and linalool (LO) significantly enhanced the circadian amplitude without altering the period. Gene expression analysis revealed that CC extract, EC, and LO altered the mRNA and protein levels of clock genes in a time-dependent manner. During molecular docking simulations, both EC and LO exhibited strong binding affinities for RORA, a key nuclear receptor involved in circadian regulation. Enhanced BMAL1 promoter activity following EC and LO treatments corroborated these findings. Furthermore, EC and LO demonstrated significant antioxidant activities, as evidenced by reduced reactive oxygen species levels and increased expression of antioxidant enzymes. EC and LO also upregulated skin barrier-related and ceramide synthesis genes and modulated the expression of cellular longevity-promoting genes. In conclusion, CC extract, particularly the components EC and LO, modulated circadian rhythms, reduced oxidative stress, and enhanced skin barrier function in keratinocytes. These findings highlight the potential of CC extract and its components as novel dermatological treatments to improve skin health and combat aging.

Keywords:  Cinnamomi cortex; Circadian rhythm; Epicatechin; Keratinocyte; Linalool

DOI:  https://doi.org/10.1038/s41598-025-88325-5
Mol Neurobiol. 2025 Feb 05.

Grape Seed Extract Pretreatment Prevents Mitochondrial Dysfunction and NLRP3 Inflammasome-Induced Inflammatory Response in Glial Cells Exposed to Paroxetine and Quinolinic Acid.

Marina Rigotti, Laura Ferrazzi Finger, Fernando Joel Scariot, Alencar Kolinski Machado, Scheila de Avila E Silva, Mirian Salvador, Catia Santos Branco.

  Depression is a neuropsychiatric disorder that affects thousands of people around the world. Drug therapy is the main approach for treating this disease, but its use can cause side effects on cells. This study aimed to examine the impact of antidepressant drugs from different classes on glial (BV-2) cells in the presence or absence of grape seed extract (GSE) and quinolinic acid (QA; 1.5 mM). Cells were treated with GSE (50 μg/mL; 23 h) and then exposed to non-cytotoxic concentrations of bupropion, imipramine, paroxetine, trazodone, and venlafaxine (27-181 µM; 1 h). Principal Component Analysis (PCA) was conducted to demonstrate the best combination of drug and extract treatment. Cell viability, adenosine triphosphate (ATP) production, reactive oxygen species (ROS) and nitric oxide (NO) levels, oxidative damage to lipids (TBARS), superoxide dismutase (SOD) activity, apoptosis, and NLR family pyrin domain containing 3 (NLRP3) genetic expression were evaluated by spectrophotometry, qRT-PCR, or flow cytometry. Mitochondrial markers (CI: NADH-CoQ reductase and CIV: cytochrome c oxidase) were also studied. GSE prevented the increment in levels of ROS (13.73-72.11%), TBARS (44.1-92.77%), NO (9.5-16%), SOD (68.44-212.29%) activity, and apoptosis (10.06-17.3%) caused by antidepressant drugs. Furthermore, it prevented impairments in complexes I (22-71.5%) and IV (7.5-92.5%) activities and ATP production (8-46%). GSE also prevented the NLRP3 overexpression in BV-2 activated by QA (62%), and paroxetine (46%), defined by PCA. Our study evidences that GSE can restore redox equilibrium and prevent inflammation caused by antidepressants and/or QA in a glial microenvironment.

Keywords:  Antidepressant drugs; Depression; Grape seed extract; Inflammation; Mitochondrial diseases; Quinolinic acid

DOI:  https://doi.org/10.1007/s12035-025-04730-x