bims-mistre 2025-01-26 papers

bims-mistre

Biomed News

on Mito stress

Issue of 2025–01–26
twenty-one papers selected by
Ellen Siobhan Mitchell, MitoQ

A potential therapeutic approach for ulcerative colitis: targeted regulation of mitochondrial dynamics and mitophagy through phytochemicals.
Oxidative Stress and Mitochondrial Impairment: Key Drivers in Neurodegenerative Disorders.
Role of cardiolipin in skeletal muscle function and its therapeutic implications.
Epigallocatechin 3-gallate-induced neuroprotection in neurodegenerative diseases: molecular mechanisms and clinical insights.
Mitochondrial quality control: Biochemical mechanism of cardiovascular disease.
Mitochondrial Calcium Homeostasis and Atrial Fibrillation: Mechanisms and Therapeutic Strategies Review.
Combined effects of natural products and exercise on apoptosis pathways in obesity-related skeletal muscle dysfunction.
Apigenin enhancing oxidative resistance and proteostasis to extend lifespan via PTEN-mediated AKT signalling pathway.
Overcoming β-Cell Dysfunction in Type 2 Diabetes Mellitus: CD36 Inhibition and Antioxidant System.
The possible role of cerebrolysin in the management of vascular dementia: Leveraging concepts.
Nature's magic: how natural products work hand in hand with mitochondria to treat stroke.
Involvement of ROS signal in aging and regulation of brain functions.
Characterizing Oxidative Stress induced by Aβ Oligomers and the Protective Role of Carnosine in Primary Mixed Glia Cultures.
Mitochondrial dysfunction in Alzheimer's disease: Guiding the path to targeted therapies.
Nicotinamide riboside supplementation ameliorates ovarian dysfunction in a PCOS mouse model.
Harnessing natural saponins: Advancements in mitochondrial dysfunction and therapeutic applications.
Ergothioneine exerts neuroprotective effects in Parkinson's disease: Targeting α-synuclein aggregation and oxidative stress.
The Effects of Astaxanthin on Metabolic Syndrome: A Comprehensive Review.
Flavins and Flavoproteins in the Neuroimmune Landscape of Stress Sensitization and Major Depressive Disorder.
Chlorogenic acid mitigates heat stress-induced oxidative damage in bovine mammary epithelial cells by inhibiting NF-κB-mediated NLRP3 inflammasome activation via upregulating the Nrf2 signaling pathway.
Silibinin's role in counteracting neuronal apoptosis and synaptic dysfunction in Alzheimer's disease models.

Front Immunol. 2024 ;15 1506292

A potential therapeutic approach for ulcerative colitis: targeted regulation of mitochondrial dynamics and mitophagy through phytochemicals.

Jianping Zhou, Yuting Xi, Ting Wu, Xiaoyu Zeng, Jun Yuan, Lei Peng, Hao Fu, Ce Zhou.

  Mitochondria are important organelles that regulate cellular energy and biosynthesis, as well as maintain the body's response to environmental stress. Their dynamics and autophagy influence occurrence of cellular function, particularly under stressful conditions. They can generate reactive oxygen species (ROS) which is a major contributor to inflammatory diseases such as ulcerative colitis (UC). In this review, we discuss the key effects of mitochondrial dynamics and mitophagy on the pathogenesis of UC, with a particular focus on the cellular energy metabolism, oxidative stress, apoptosis, and immunoinflammatory activities. The therapeutic efficacy of existing drugs and phytochemicals targeting the mitochondrial pathway are discussed to reveal important insights for developing therapeutic strategies for treating UC. In addition, new molecular checkpoints with therapeutic potential are identified. We show that the integration of mitochondrial biology with the clinical aspects of UC may generate ideas for enhancing the clinical management of UC.

Keywords:  UC; mitochondrial dynamics; mitophagy; nature products; targeted therapy

DOI:  https://doi.org/10.3389/fimmu.2024.1506292
Ageing Res Rev. 2025 Jan 21. pii: S1568-1637(25)00013-3. [Epub ahead of print] 102667

Oxidative Stress and Mitochondrial Impairment: Key Drivers in Neurodegenerative Disorders.

Pei Wen, Zhixin Sun, Fengting Gou, Jingjing Wang, Qing Fan, Deming Zhao, Lifeng Yang.

  Mitochondrial dysfunction and oxidative stress are critical factors in the pathogenesis of neurodegenerative diseases. The complex interplay between these factors exacerbates neuronal damage and accelerates disease progression. In neurodegenerative diseases, mitochondrial dysfunction impairs ATP production and promotes the generation of reactive oxygen species (ROS). The accumulation of ROS further damages mitochondrial DNA, proteins, and lipids, creating a vicious cycle of oxidative stress and mitochondrial impairment. This review aims to elucidate the mechanisms by which mitochondrial dysfunction and oxidative stress lead to neurodegeneration, and to highlight potential therapeutic targets to mitigate their harmful effects.

Keywords:  Mitochondrial Dysfunction; Neurodegenerative Diseases; Oxidative Stress; ROS

DOI:  https://doi.org/10.1016/j.arr.2025.102667
Cell Commun Signal. 2025 Jan 21. 23(1): 36

Role of cardiolipin in skeletal muscle function and its therapeutic implications.

Youngbum Yoo, MyeongHoon Yeon, Mee-Sup Yoon, Young-Kyo Seo.

  Cardiolipin, a unique phospholipid predominantly present in the inner mitochondrial membrane, is critical for maintaining mitochondrial integrity and function. Its dimeric structure and role in supporting mitochondrial dynamics, energy production, and mitophagy make it indispensable for skeletal muscle health. This review provides a comprehensive overview of cardiolipin biosynthesis, remodeling processes, and essential functions within mitochondria. We explore the influences of cardiolipin on the stability of the mitochondrial complexes, cristae formation, and calcium handling, all of which are vital for efficient oxidative phosphorylation and muscle contraction. Skeletal muscle, with its high energy demands, is particularly dependent on cardiolipin for optimal performance. We discuss the impact of aging on cardiolipin levels, which correlates with a decline in mitochondrial function and muscle mass, contributing to conditions such as sarcopenia. Furthermore, we examined the relationship between cardiolipin and endurance exercise, highlighting the effects of exercise-induced increase in cardiolipin levels on the improvement of mitochondrial function and muscle health. The role of Crls1 in cardiolipin synthesis has been emphasized as a potential therapeutic target for the treatment of sarcopenia. Increasing cardiolipin levels through gene therapy, pharmacological interventions, or specific exercise and nutritional strategies holds promise for mitigating muscle atrophy and promoting muscle regeneration. By focusing on the multifaceted role of cardiolipin in mitochondria and muscle health, we aimed to provide new insights into therapeutic approaches for enhancing muscle function and combating age-related muscle decline.

Keywords:   Crls1 ; Cardiolipin; Exercise; Mitochondrial function; Muscle atrophy; Oxidative phosphorylation; Sarcopenia; Skeletal muscle

DOI:  https://doi.org/10.1186/s12964-025-02032-2
Mol Cell Biochem. 2025 Jan 20.

Epigallocatechin 3-gallate-induced neuroprotection in neurodegenerative diseases: molecular mechanisms and clinical insights.

Md Rezaul Islam, Abdur Rauf, Sumiya Akter, Happy Akter, Md Ibrahim Khalil Al-Imran, Samiul Islam, Meherun Nessa, Chaity Jahan Shompa, Md Nabil Rihan Shuvo, Imtiaz Khan, Waleed Al Abdulmonem, Abdullah S M Aljohani, Muhammad Imran, Marcello Iriti.

  Neurodegenerative diseases (NDs) are caused by progressive neuronal death and cognitive decline. Epigallocatechin 3-gallate (EGCG) is a polyphenolic molecule in green tea as a neuroprotective agent. This review evaluates the therapeutic effects of EGCG and explores the molecular mechanisms that show its neuroprotective properties. EGCG protects neurons in several ways, such as by lowering oxidative stress, stopping Aβ from aggregation together, changing cell signaling pathways, and decreasing inflammation. Furthermore, it promotes autophagy and improves mitochondrial activity, supporting neuronal survival. Clinical studies have demonstrated that EGCG supplementation can reduce neurodegenerative biomarkers and enhance cognitive function. This review provides insights into the molecular mechanisms and therapeutic potential of EGCG in treating various NDs. EGCG reduces oxidative stress by scavenging free radicals and enhancing antioxidant enzyme activity, aiding neuronal defense. It also protects neurons and improves cognitive abilities by inhibiting the toxicity and aggregation of Aβ peptides. It changes important cell signaling pathways like Nrf2, PI3K/Akt, and MAPK, which are necessary for cell survival, cell death, and inflammation. Additionally, it has strong anti-inflammatory properties because it inhibits microglial activation and downregulates pro-inflammatory cytokines. It improves mitochondrial function by reducing oxidative stress, increasing ATP synthesis, and promoting mitochondrial biogenesis, which promotes neurons' survival and energy metabolism. In addition, it also triggers autophagy, a cellular process that breaks down and recycles damaged proteins and organelles, eliminating neurotoxic aggregates and maintaining cellular homeostasis. Moreover, it holds significant promise as an ND treatment, but future research should focus on increasing bioavailability and understanding its long-term clinical effects. Future studies should focus on improving EGCG delivery and understanding its long-term effects in therapeutic settings. It can potentially be a therapeutic agent for managing NDs, indicating a need for further research.

Keywords:  Clinical insights; Epigallocatechin 3-gallate; Molecular mechanisms; Neurodegeneration; Neuroprotection

DOI:  https://doi.org/10.1007/s11010-025-05211-4
Biochim Biophys Acta Mol Cell Res. 2025 Jan 19. pii: S0167-4889(25)00011-4. [Epub ahead of print]1872(3): 119906

Mitochondrial quality control: Biochemical mechanism of cardiovascular disease.

Francesca Inferrera, Ylenia Marino, Tiziana Genovese, Salvatore Cuzzocrea, Roberta Fusco, Rosanna Di Paola.

  Mitochondria play a key role in the regulation of energy homeostasis and ATP production in cardiac cells. Mitochondrial dysfunction can trigger several pathological events that contribute to the development and progression of cardiovascular diseases. These mechanisms include the induction of oxidative stress, dysregulation of intracellular calcium cycling, activation of the apoptotic pathway, and alteration of lipid metabolism. This review focuses on the role of mitochondria in intracellular signaling associated with cardiovascular diseases, emphasizing the contributions of reactive oxygen species production and mitochondrial dynamics. Indeed, mitochondrial dysfunction has been implicated in every aspect of cardiovascular disease and is currently being evaluated as a potential target for therapeutic interventions. To treat cardiovascular diseases and improve overall heart health, it is important to better understand these biochemical systems. These findings allow the achievement of targeted therapies and preventive measures. Therefore, this review investigates different studies that demonstrate how changes in mitochondrial dynamics like fusion, fission, and mitophagy contribute to the development or worsening of disorders related to heart diseases by summarizing current research on their role.

Keywords:  Cardiovascular diseases; Intracellular signaling; Mitochondrial dysfunction; Oxidative stress; Therapeutic interventions

DOI:  https://doi.org/10.1016/j.bbamcr.2025.119906
Curr Probl Cardiol. 2025 Jan 17. pii: S0146-2806(25)00011-8. [Epub ahead of print] 102988

Mitochondrial Calcium Homeostasis and Atrial Fibrillation: Mechanisms and Therapeutic Strategies Review.

Yixuan Chang, Qi Zou.

Atrial fibrillation (AF) is tightly linked to mitochondrial dysfunction, calcium (Ca²⁺) imbalance, and oxidative stress. Mitochondrial Ca²⁺ is essential for regulating metabolic enzymes, maintaining the tricarboxylic acid (TCA) cycle, supporting the electron transport chain (ETC), and producing ATP. Additionally, Ca²⁺ modulates oxidative balance by regulating antioxidant enzymes and reactive oxygen species (ROS) clearance. However, Ca²⁺ homeostasis disruptions, particularly overload, result in excessive ROS production, mitochondrial permeability transition pore (mPTP) opening, and oxidative stress-induced damage. These changes lead to mitochondrial dysfunction, Ca²⁺ leakage, and cardiomyocyte apoptosis, driving AF progression and atrial remodeling. Therapeutically, targeting mitochondrial Ca²⁺ homeostasis shows promise in mitigating AF. Moderate Ca²⁺ regulation enhances energy metabolism, stabilizes mitochondrial membrane potential, and bolsters antioxidant defenses by upregulating enzymes like superoxide dismutase and glutathione peroxidase. This reduces ROS generation and facilitates clearance. Proper Ca²⁺ levels also prevent electron leakage and promote mitophagy, aiding in damaged mitochondria removal and reducing ROS accumulation. Future strategies include modulating Ryanodine receptor 2 (RyR2), mitochondrial calcium uniporter (MCU), and sodium-calcium exchanger (NCLX) to control Ca²⁺ overload and oxidative damage. Addressing mitochondrial Ca²⁺ dynamics offers a compelling approach to breaking the cycle of Ca²⁺ overload, oxidative stress, and AF progression. Further research is needed to clarify the mechanisms of mitochondrial Ca²⁺ regulation and its role in AF pathogenesis. This knowledge will guide the development of innovative treatments to improve outcomes and quality of life for AF patients.

DOI: https://doi.org/10.1016/j.cpcardiol.2025.102988
Apoptosis. 2025 Jan 20.

Combined effects of natural products and exercise on apoptosis pathways in obesity-related skeletal muscle dysfunction.

Chun Pan, Yiying Yang, Zailin Zhao, Jingye Hu.

  Obesity and related metabolic disorders are closely linked to increased apoptosis in skeletal muscle, leading to muscle degeneration, insulin resistance, and the progression of diseases such as type 2 diabetes and sarcopenia. This review explores the combined effects of natural products, including resveratrol, curcumin, and quercetin, and physical exercise on modulating apoptosis pathways in skeletal muscle. Both natural products and regular physical activity independently reduce oxidative stress and improve mitochondrial function, thereby regulating the balance between pro-apoptotic and anti-apoptotic signals. When combined, these interventions amplify their protective effects on muscle health, promoting mitochondrial biogenesis, reducing apoptosis, and enhancing muscle regeneration. This review also discusses the molecular mechanisms by which these strategies influence apoptosis, with a focus on the Bcl-2 pathway, and explores the clinical implications for the prevention and treatment of obesity-related diseases. The synergistic benefits of combining exercise with natural product supplementation offer a promising therapeutic approach for managing metabolic disorders, preserving muscle function, and improving overall metabolic health.

Keywords:  Apoptosis; Exercise; Natural products; Oxidative stress; Skeletal muscle

DOI:  https://doi.org/10.1007/s10495-024-02069-7
Biochim Biophys Acta Mol Basis Dis. 2025 Jan 16. pii: S0925-4439(25)00015-8. [Epub ahead of print] 167670

Apigenin enhancing oxidative resistance and proteostasis to extend lifespan via PTEN-mediated AKT signalling pathway.

Zhengqiong Sun, Lei Li, Lei Zhang.

  Aging is a complicated process, featuring the progressive deterioration of physiological functions and a heightened susceptibility to diseases including neurodegenerative disorders, cardiovascular diseases, and cancer. Apigenin, a flavonoid existing in various plants, has attracted attention due to its potential role in anti-aging. In this investigation, the potential effect of apigenin on extending lifespan in Saccharomyces cerevisiae (yeast) and Drosophila melanogaster (flies) was explored. The results indicate that apigenin significantly extends both replicative and chronological life duration in yeast, as well as longevity in male and female flies. Apigenin treatment also improves resistance to oxidative stress in both organisms, as manifested by enhanced survival, decreased reactive oxygen species (ROS) levels and upregulation of antioxidant enzymes. Furthermore, apigenin activates crucial elements of the proteostasis network (PN), such as upregulation of proteostasis-related enzymes activity and genes expression. Network analysis revealed that apigenin affects aging conserved in the longevity-regulating pathway. Notably, Pten is a hub target in flies. Apigenin regulated DmPten at both mRNA and protein expression level while modulating downstream targets, including the phosphorylation of AKT and associated signalling pathways. In a high-sucrose diet (HSD) model, Apigenin treatment extended lifespan, reduced hemolymph glucose levels, enhanced Pten expression, suppressed AKT phosphorylation, and modulated the phosphorylation status of S6K and expression of DmFoxo. These results demonstrate that apigenin could serve as a longevity research object and potential therapeutic drug for promoting health and longevity through its antioxidant and proteostatic properties.

Keywords:  Aging; Antioxidant; Apigenin; Diabetes; Network pharmacology; PTEN; Proteostasis

DOI:  https://doi.org/10.1016/j.bbadis.2025.167670
Diabetes Metab J. 2025 Jan;49(1): 1-12

Overcoming β-Cell Dysfunction in Type 2 Diabetes Mellitus: CD36 Inhibition and Antioxidant System.

Il Rae Park, Yong Geun Chung, Kyu Chang Won.

  Type 2 diabetes mellitus (T2DM) is marked by chronic hyperglycemia, gradually worsening β-cell failure, and insulin resistance. Glucotoxicity and oxidative stress cause β-cell failure by increasing reactive oxygen species (ROS) production, impairing insulin secretion, and disrupting transcription factors such as pancreatic and duodenal homeobox 1 (PDX-1) and musculoaponeurotic fibrosarcoma oncogene family A (MafA). Cluster determinant 36 (CD36), an essential glycoprotein responsible for fatty acid uptake, exacerbates oxidative stress and induces the apoptosis of β-cells under hyperglycemic conditions through pathways involving ceramide, thioredoxin-interacting protein (TXNIP), and Rac1-nicotinamide adenine dinucleotide phosphate oxidase (NOX)-mediated redoxosome formation. Targeting CD36 pathways has emerged as a promising therapeutic strategy. Oral hypoglycemic agents, such as metformin, teneligliptin, and pioglitazone, have shown protective effects on β-cells by enhancing antioxidant defenses. These agents reduce glucotoxicity via mechanisms such as suppressing CD36 expression and stabilizing mitochondrial function. Additionally, novel insights into the glutathione antioxidant system and its role in β-cell survival underscore its therapeutic potential. This review focuses on the key contribution of oxidative stress and CD36 to β-cell impairment, the therapeutic promise of antioxidants, and the need for further research to apply these findings in clinical practice. Promising strategies targeting these mechanisms may help preserve β-cell function and slow T2DM progression.

Keywords:  CD36 antigens; Diabetes mellitus, type 2; Hyperglycemia; Insulin-secreting cells; Oxidative stress; Reactive oxygen species

DOI:  https://doi.org/10.4093/dmj.2024.0796
Neuroscience. 2025 Jan 19. pii: S0306-4522(25)00050-8. [Epub ahead of print]568 202-208

The possible role of cerebrolysin in the management of vascular dementia: Leveraging concepts.

Hayder M Al-Kuraishy, Ali I Al-Gareeb, Salwa H Zekry, Mubarak Alruwaili, Athanasios Alexiou, Marios Papadakis, Gaber El-Saber Batiha.

  Cerebrolysin (CBL) is a combination of neurotrophic peptides and amino acids derived from pig brains. CBL can cross the blood-brain barrier (BBB) and its biological effect is similar to the effect of endogenous neurotrophic effects. The mechanism of action of CBL is related to the induction of neurogenesis, neuroplasticity, neuroprotection, and neurotrophicity. Therefore, CBL may be effective against the development and progression of neurodegenerative diseases such as Alzheimer disease (AD) and cerebrovascular disorders such as vascular dementia (VD). Moreover, many studies highlighted that CBL is effective in the improvement of cognitive impairment in patients with neurodegenerative diseases. However, the underlying neuroprotective effects of CBL against the VD neuropathology were not fully elucidated. Thus, this review aims to discuss the possible therapeutic efficacy of CBL in the management of VD. In conclusion, CBL could be effective therapeutic strategy in preventing and treating VD by targeting neuroinflammation, BBB injury, and chronic cerebral hypoperfusion.

Keywords:  Cerebrolysin; Hypoperfusion; Neuroprotection; Oxidative stress; Vascular dementia

DOI:  https://doi.org/10.1016/j.neuroscience.2025.01.040
Front Pharmacol. 2024 ;15 1434948

Nature's magic: how natural products work hand in hand with mitochondria to treat stroke.

Lin Cheng, Shangbin Lv, Chengkai Wei, Sucheng Li, Hao Liu, Yong Chen, Zhaoliang Luo, Hongyan Cui.

   Background: Mitochondria, as the energy factories of cells, are involved in a wide range of vital activities, including cell differentiation, signal transduction, the cell cycle, and apoptosis, while also regulating cell growth. However, current pharmacological treatments for stroke are challenged by issues such as drug resistance and side effects, necessitating the exploration of new therapeutic strategies.
Objective: This review aims to summarize the regulatory effects of natural compounds targeting mitochondria on neuronal mitochondrial function and metabolism, providing new perspectives for stroke treatment.
Main findings: Numerous in vitro and in vivo studies have shown that natural products such as berberine, ginsenosides, and baicalein protect neuronal mitochondrial function and reduce stroke-induced damage through multiple mechanisms. These compounds reduce neuronal apoptosis by modulating the expression of mitochondrial-associated apoptotic proteins. They inhibit the activation of the mitochondrial permeability transition pore (mPTP), thereby decreasing ROS production and cytochrome C release, which helps preserve mitochondrial function. Additionally, they regulate ferroptosis, mitochondrial fission, and promote mitochondrial autophagy and trafficking, further enhancing neuronal protection.
Conclusion: As multi-target chemical agents, natural products offer high efficacy with fewer side effects and present promising potential for innovative stroke therapies. Future research should further investigate the effectiveness and safety of these natural products in clinical applications, advancing their development as a new therapeutic strategy for stroke.

Keywords:  ischaemic injury; mitochondria; natural products; neuronal protection; stroke

DOI:  https://doi.org/10.3389/fphar.2024.1434948
J Physiol Sci. 2024 Dec 21. pii: S1880-6546(24)00984-3. [Epub ahead of print]75(1): 100003

Involvement of ROS signal in aging and regulation of brain functions.

Sho Kakizawa.

  Reactive oxygen species (ROS) are redox-signaling molecules involved in aging and lifestyle-related diseases. In the brain, in addition to the production of ROS as byproducts of metabolism, expression of ROS synthases has recently been demonstrated, suggesting possible involvement of ROS in various brain functions. This review highlights current knowledge on the relationship between ROS and brain functions, including their contribution to age-related decline in synaptic plasticity and cognitive function. While most studies demonstrate either the positive or negative effects of ROS on synaptic plasticity, the dual effects of ROS at individual synapses have been demonstrated recently in the mouse cerebellum. Furthermore, the cooperative interaction between these two effects determines the direction of synaptic plasticity. It is anticipated that further elucidation of both the positive and negative effects of ROS on brain function will lead to the development of more effective therapeutic strategies with fewer side effects for ROS-related brain dysfunction.

Keywords:  Aging; Cerebellum; Long-term depression; Long-term potentiation; Reactive oxygen species; Synaptic plasticity

DOI:  https://doi.org/10.1016/j.jphyss.2024.100003
Free Radic Biol Med. 2025 Jan 15. pii: S0891-5849(25)00030-9. [Epub ahead of print]

Characterizing Oxidative Stress induced by Aβ Oligomers and the Protective Role of Carnosine in Primary Mixed Glia Cultures.

Vincenzo Cardaci, Lucia Di Pietro, Matthew C Zupan, Jay Sibbitts, Anna Privitera, Susan M Lunte, Filippo Caraci, Meredith D Hartley, Giuseppe Caruso.

  Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive decline and memory loss. A critical aspect of AD pathology is represented by oxidative stress, which significantly contributes to neuronal damage and death. Microglia and astrocytes, the primary glial cells in the brain, are crucial for managing oxidative stress and supporting neuronal function. Carnosine is an endogenous dipeptide possessing a multimodal mechanism of action that includes antioxidant, anti-inflammatory, and anti-aggregant activities. The present study investigated the effects of Aβ1-42 oligomers (oAβ), small aggregates associated with the neurodegeneration observed in AD, on primary rat mixed glia cultures composed of both microglia and astrocytes, focusing on the ability of these detrimental species to induce oxidative stress. We assessed intracellular reactive oxygen species (ROS) and nitric oxide (NO) levels as markers of oxidative stress. Exposure to oAβ significantly elevated both ROS and NO intracellular levels compared to control cells. However, this effect was completely inhibited by the pre-treatment of mixed cultures with carnosine, resulting in ROS and NO levels similar to those observed in untreated (control) cells. Single-cell analysis of cellular responses to oAβ revealed heterogeneous ROS production, resulting in two distinct clusters of cells, one of which was very responsive to the treatment. The presence of carnosine counteracted the overproduction of ROS, also leading to a single, homogeneous cluster, similar to that observed in the case of control cells. Interestingly, unlike ROS response, single-cell analysis of NO production did not show any distinct clusters. Overall, our findings demonstrated the ability of carnosine to mitigate Aβ-induced oxidative stress in mixed glia cells, by rescuing ROS and NO intracellular levels, as well as to normalize the heterogeneous response to the treatment measured in terms of clusters' formation. The present study suggests a therapeutic potential of carnosine in pathologies characterized by oxidative stress including AD.

Keywords:  Alzheimer’s disease; Astrocytes; Carnosine; Microglia; Neurodegeneration; Oxidative stress; Reactive oxygen species

DOI:  https://doi.org/10.1016/j.freeradbiomed.2025.01.030
Neurotherapeutics. 2025 Jan 17. pii: S1878-7479(25)00003-0. [Epub ahead of print] e00525

Mitochondrial dysfunction in Alzheimer's disease: Guiding the path to targeted therapies.

Kyle C McGill Percy, Zhunren Liu, Xin Qi.

  Alzheimer's disease (AD) is characterized by progressive neurodegeneration, marked by the accumulation of amyloid-β (Aβ) plaques and tau tangles. Emerging evidence suggests that mitochondrial dysfunction plays a pivotal role in AD pathogenesis, driven by impairments in mitochondrial quality control (MQC) mechanisms. MQC is crucial for maintaining mitochondrial integrity through processes such as proteostasis, mitochondrial dynamics, mitophagy, and precise communication with other subcellular organelles. In AD, disruptions in these processes lead to bioenergetic failure, gene dysregulation, the accumulation of damaged mitochondria, neuroinflammation, and lipid homeostasis impairment, further exacerbating neurodegeneration. This review elucidates the molecular pathways involved in MQC and their pathological relevance in AD, highlighting recent discoveries related to mitochondrial mechanisms underlying neurodegeneration. Furthermore, we explore potential therapeutic strategies targeting mitochondrial dysfunction, including gene therapy and pharmacological interventions, offering new avenues for slowing AD progression. The complex interplay between mitochondrial health and neurodegeneration underscores the need for innovative approaches to restore mitochondrial function and mitigate the onset and progression of AD.

Keywords:  Alzheimer's disease; Amyloid beta; Gene therapy; Mitochondrial quality control; Pharmacotherapy; Tauopathy

DOI:  https://doi.org/10.1016/j.neurot.2025.e00525
J Ovarian Res. 2025 Jan 20. 18(1): 9

Nicotinamide riboside supplementation ameliorates ovarian dysfunction in a PCOS mouse model.

Zhenye Zhu, Min Lei, Ruizhi Guo, Yining Xu, Yanqing Zhao, Chenlu Wei, Qingling Yang, Yingpu Sun.

  Polycystic ovary syndrome (PCOS) is the leading cause of anovulatory infertility among women of reproductive age, yet the range of effective treatment options remains limited. Our previous study revealed that reduced levels of nicotinamide adenine dinucleotide (NAD+) in ovarian granulosa cells (GCs) of women with PCOS resulted in the accumulation of reactive oxygen species (ROS) and mitochondrial dysfunction. However, it is still uncertain whether increasing NAD+ levels in the ovaries could improve ovarian function in PCOS. In this study, we demonstrated that supplementation with the NAD+ precursor nicotinamide riboside (NR) prevented the decrease in ovarian NAD+ levels, normalized estrous cycle irregularities, and enhanced ovulation potential in dehydroepiandrosterone (DHEA)-induced PCOS mice. Moreover, NR supplementation alleviated ovarian fibrosis and enhanced mitochondrial function in ovarian stromal cells of PCOS mice. Furthermore, NR supplementation improved oocyte quality in PCOS mice, as evidenced by reduced abnormal mitochondrial clustering, enhanced mitochondrial membrane potential, decreased ROS levels, reduced spindle abnormality rates, and increased early embryonic development potential in fertilized oocytes. These findings suggest that supplementing with NAD+ precursors could be a promising therapeutic strategy for addressing ovarian infertility associated with PCOS.

Keywords:  Fibrosis; Mitochondrial; Nicotinamide adenine dinucleotide; Nicotinamide riboside; Ovary; Polycystic ovary syndrome

DOI:  https://doi.org/10.1186/s13048-025-01596-4
Phytomedicine. 2025 Jan 10. pii: S0944-7113(25)00022-4. [Epub ahead of print]138 156383

Harnessing natural saponins: Advancements in mitochondrial dysfunction and therapeutic applications.

Hongmei Liu, Huan Wang, Xinyu Lin, Min Xu, Wenying Lan, Jinlian Wang.

   BACKGROUND: Mitochondrial dysfunction plays a crucial role in the development of a variety of diseases, notably neurodegenerative disorders, cardiovascular diseases, metabolic syndrome, and cancer. Natural saponins, which are intricate glycosides characterized by steroidal or triterpenoid structures, have attracted interest due to their diverse pharmacological benefits, including anti-inflammatory, antiviral, and anti-aging effects.
PURPOSE: This review synthesizes recent advancements in understanding mitochondrial dysfunction and explores how saponins can modulate mitochondrial function. It focuses on their potential applications in neuroprotection, cardiovascular health, and oncology.
STUDY DESIGN: The review incorporates a comprehensive literature analysis, highlighting the interplay between saponins and mitochondrial signaling pathways. Specific attention is given to the effects of saponins like ginsenoside Rg2 and 20(S)-protopanaxatriol on mitophagy and their neuroprotective, anti-aging, and synergistic therapeutic effects when combined.
METHODS: We conducted a comprehensive review of current research and clinical trials using PubMed, Google Scholar, and SciFinder databases. The search focused on saponins' role in mitochondrial function and their therapeutic effects, including "saponins", "mitochondria" and "mitochondrial function". The analysis primarily focused on articles published between 2011 and 2024.
RESULTS: The findings indicate that certain saponins can enhance mitophagy and modulate mitochondrial signaling pathways, showing promise in neuroprotection and anti-aging. Additionally, combinations of saponins have demonstrated synergistic effects in myocardial protection and cancer therapy, potentially improving therapeutic outcomes.
CONCLUSION: Although saponins exhibit significant potential in modulating mitochondrial functions and developing innovative therapeutic strategies, their clinical applications are constrained by low bioavailability. Rigorous clinical trials are essential to translate these findings into effective clinical therapies, ultimately improving patient outcomes through a deeper understanding of saponins' impact on mitochondrial function.

Keywords:  Bioavailability; Mitochondrial dysfunction; Natural product; Saponins; Therapeutic potential

DOI:  https://doi.org/10.1016/j.phymed.2025.156383
Food Res Int. 2025 Feb;pii: S0963-9969(24)01661-2. [Epub ahead of print]201 115590

Ergothioneine exerts neuroprotective effects in Parkinson's disease: Targeting α-synuclein aggregation and oxidative stress.

Wen Gao, Yang Wang, Fuhao Wang, Xinni Wu, Fuping Lu, Fufeng Liu.

  Ergothioneine (EGT) is a natural dietary antioxidant derived from certain edible mushrooms, commonly used as a food additive and supplement, but its effects on Parkinson's Disease (PD) are still unclear. The accumulation of α-synuclein (α-syn) plays a pivotal role in the pathogenesis and development of PD. Here, this study demonstrated that EGT effectively inhibits α-syn aggregation, disrupts mature fibers, and reduces associated cytotoxicity and oxidative stress. The beneficial effects of EGT were confirmed in Caenorhabditis elegans, where it protected dopaminergic neurons, prolonged lifespan and enhanced behavioral functions by reducing α-syn plaque accumulation and associated oxidative stress. Molecular dynamics simulation revealed that EGT interacts directly with α-syn pentamer through van der Waals and electrostatic forces, disrupting the structural stability of the preformed pentamer. Furthermore, animal studies validated that EGT alleviated neuronal damage and improved behavioral deficits by reducing α-syn aggregation, oxidative stress and inflammatory response. In conclusion, EGT presents promising potential as a dietary supplement for preventing and alleviating PD.

Keywords:  Ergothioneine; Food supplement; Oxidative stress; Parkinson’s disease; α-synuclein

DOI:  https://doi.org/10.1016/j.foodres.2024.115590
Mar Drugs. 2024 Dec 27. pii: 9. [Epub ahead of print]23(1):

The Effects of Astaxanthin on Metabolic Syndrome: A Comprehensive Review.

Chunhao Gao, Nengyun Gong, Fangtian Chen, Shiran Hu, Qingxin Zhou, Xiang Gao.

  Metabolic syndrome (MS) represents a complex cluster of metabolic disorders primarily characterized by obesity, insulin resistance, hyperglycemia, dyslipidemia, hypertension, and hyperuricemia. Diet and functional ingredients play a pivotal role in seeking non-pharmacological strategies to prevent and ameliorate MS. Astaxanthin (AST), a carotenoid found in various marine organisms, exhibits exceptional antioxidant properties and holds great promise as a natural compound that improves MS. This article introduces the basic properties of AST, including its absorptance and metabolic pathways, along with various isomers. Most importantly, we comprehensively review the effects and mechanisms of AST on improving the primary components of MS. These mechanisms primarily involve regulating signal transduction, transport, or metabolic pathways within the body, as well as influencing intestinal microbiota and metabolites, thereby exerting positive effects on metabolism and inhibiting the occurrence of MS. This review emphasizes the potential efficacy of AST in managing MS. However, more studies are needed to confirm the clinical effect of AST on MS and reveal potential molecular mechanisms.

Keywords:  astaxanthin; dyslipidemia; insulin resistance; metabolic syndrome; obesity

DOI:  https://doi.org/10.3390/md23010009
J Inflamm Res. 2025 ;18 681-699

Flavins and Flavoproteins in the Neuroimmune Landscape of Stress Sensitization and Major Depressive Disorder.

Matt Scott Schrier, Maria Igorevna Smirnova, Daniel Paul Nemeth, Richard Carlton Deth, Ning Quan.

  Major Depressive Disorder (MDD) is a common and severe neuropsychiatric condition resulting in irregular alterations in affect, mood, and cognition. Besides the well-studied neurotransmission-related etiologies of MDD, several biological systems and phenomena, such as the hypothalamic-pituitary-adrenal (HPA) axis, reactive oxygen species (ROS) production, and cytokine signaling, have been implicated as being altered and contributing to depressive symptoms. However, the manner in which these factors interact with each other to induce their effects on MDD development has been less clear, but is beginning to be understood. Flavins are potent biomolecules that regulate many redox activities, including ROS generation and energy production. Studies have found that circulating flavin levels are modulated during stress and MDD. Flavins are also known for their importance in immune responses. This review offers a unique perspective that considers the redox-active cofactors, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), as vital substrates for linking MDD-related maladaptive processes together, by permitting stress-induced enhancement of microglial interleukin-1 beta (IL-1β) signaling.

Keywords:  IL-1β; cofactor; cytokines; microglia; neuroinflammation; redox

DOI:  https://doi.org/10.2147/JIR.S501652
Int J Biol Macromol. 2025 Jan 20. pii: S0141-8130(25)00682-8. [Epub ahead of print] 140133

Chlorogenic acid mitigates heat stress-induced oxidative damage in bovine mammary epithelial cells by inhibiting NF-κB-mediated NLRP3 inflammasome activation via upregulating the Nrf2 signaling pathway.

Qi Huang, Qiang Shan, Fengtao Ma, Shengli Li, Peng Sun.

  Chlorogenic acid (CGA), a polyphenolic bioactive molecule derived from medicinal plants, is known for its strong antioxidant and anti-inflammatory properties. Previous studies have demonstrated that dietary supplementation with Lonicera japonica extract, rich in CGA, effectively enhances the production performance of lactating dairy cows under heat stress (HS) conditions. However, the molecular mechanisms underlying CGA's protective effects remain unclear. This study aims to elucidate the mechanisms by which CGA alleviates HS-induced oxidative damage in bovine mammary epithelial cells (bMECs), focusing on its pharmacological activity and potential application as a natural therapeutic agent for bovine mammary disorders. The results demonstrated that HS activates the NF-κB and NLRP3 signaling pathways by increasing ROS generation, leading to oxidative stress and inflammatory response in bMECs. CGA mitigates these effects by scavenging intracellular ROS, activating the Nrf2 signaling pathway, and inhibiting key molecules in the NF-κB and NLRP3 signaling pathways. This study provides new insights into the underlying molecular mechanisms of CGA's protective effects, highlighting its potential as a natural antioxidant for bovine mammary health and contributing to the broader application of polyphenolic compounds in managing oxidative stress and inflammation.

Keywords:  Chlorogenic acid; Inflammatory response; Oxidative damage

DOI:  https://doi.org/10.1016/j.ijbiomac.2025.140133
Apoptosis. 2025 Jan 20.

Silibinin's role in counteracting neuronal apoptosis and synaptic dysfunction in Alzheimer's disease models.

Baohui Zhang, Di Zhang, Keyan Chen, Tengfei Wu.

  This study investigates silibinin's capacity to mitigate Alzheimer's disease (AD) pathologies with a particular emphasis on its effects on apoptosis and synaptic dysfunction in AD models. Employing APP/PS1 transgenic mice and SH-SY5Y neuroblastoma cell lines, our research assessed the efficacy of silibinin in reducing amyloid-beta (Aβ) deposition, neuroinflammation, and neuronal apoptosis. Our results demonstrate that silibinin significantly decreases Aβ accumulation and neuroinflammation and robustly inhibits apoptosis in neuronal cells. Additionally, silibinin enhances the expression of synaptic proteins, thereby supporting synaptic integrity. Through network pharmacology analysis, we identified potential targets of silibinin in Aβ metabolism and synaptic functions. Mechanistically, our findings suggest that silibinin promotes neuronal survival predominantly via the modulation of the Fyn/GluN2B/CaMKIIα signaling pathway, which protects against Aβ1-42-induced apoptosis. These insights highlight silibinin's potential as a therapeutic agent for AD, particularly its role in reducing neuronal apoptosis and maintaining synaptic function.

Keywords:  Alzheimer's disease; Aβ deposition; Fyn/GluN2B/CaMKIIα signaling pathway; Neuroprotection; Silibinin; Synaptic dysfunction

DOI:  https://doi.org/10.1007/s10495-024-02073-x