bims-mistre 2025-06-29 papers

bims-mistre

Biomed News

on Mito stress

Issue of 2025–06–29
fourteen papers selected by
Ellen Siobhan Mitchell, MitoQ

Mitochondrial-Derived Peptides as Therapeutics and Biomarkers for Combating Vascular Aging and Associated Cardiovascular Diseases.
Impact of a Formulation Containing Chaga Extract, Coenzyme Q10, and Alpha-Lipoic Acid on Mitochondrial Dysfunction and Oxidative Stress: NMR Metabolomic Insights into Cellular Energy.
Crosstalk between oxidative stress, mitochondrial dysfunction, chromosome instability, and the activation of the cGAS-STING/IFN pathway in systemic sclerosis.
Evaluating Cell-Free Circulatory Mitochondrial DNA as a Comprehensive Biomarker for Stress: Meta-Analysis of Psychological and Physiological Stress Responses.
Involvement of Oxidative Stress in Mitochondrial Abnormalities During the Development of Heart Disease.
Saliva and blood cell-free mtDNA reactivity to acute psychosocial stress.
Neuroprotective potential of quercetin in Alzheimer's disease: targeting oxidative stress, mitochondrial dysfunction, and amyloid-β aggregation.
Environmental nanoplastics induce mitochondrial dysfunction: A review of cellular mechanisms and associated diseases.
Mitophagy as a therapeutic target for myocardial fibrosis: Mechanistic insights and potential pharmacological interventions.
Lithocholic Acid, Calorie Restriction, and Halting Aging.
Mechanisms of endothelial senescence and vascular aging.
The role and mechanism of PGC-1α in oxLDL-induced ferroptosis of vascular endothelial cells.
Chlorogenic acid mitigates DHEA-induced oxidative stress in granulosa cells and alleviates ferroptosis via the NF-κB signaling pathway in PCOS.
Honokiol rescues progranulin deficiency in pathogen-induced and genetically driven neurodegeneration: Bridging veterinary models with therapeutic development.

Curr Cardiol Rev. 2025 Jun 20.

Mitochondrial-Derived Peptides as Therapeutics and Biomarkers for Combating Vascular Aging and Associated Cardiovascular Diseases.

Rooban Sivakumar, K A Arul Senghor, V M Vinodhini, Janardhanan Kumar.

  Vascular aging profoundly affects the onset of cardiovascular diseases in the elderly, mostly as a result of mitochondrial dysfunction. This review examines the protective roles of mitochondrial-derived peptides such as humanin, MOTS-c, and small humanin-like peptides in mitigating vascular aging. These peptides, encoded by mitochondrial DNA, are crucial for regulating apoptosis, inflammation, and oxidative stress, which have a major role in vascular health. MDPs have significant prospects as therapeutic and biomarker possibilities for the early diagnosis and intervention of vascular aging. MDPs influence the functions of endothelial and vascular smooth muscle cells by modulating critical signaling pathways, including AMPK, mTOR, and sirtuins. These pathways are essential for facilitating cellular metabolism, enhancing stress resilience, and prolonging longevity. Moreover, MDPs are essential in mitochondrial bioenergetics and dynamics, vital for mitigating endothelial dysfunction and enhancing vascular resilience. Furthermore, MDPs contribute to immunological modulation and the regulation of inflammatory responses, underscoring their potential therapeutic applications in the treatment of age-related vascular disorders. This review analyzes the various functions of MDPs in vascular health and their therapeutic importance, advocating for more studies to optimize their clinical benefits. By understanding the comprehensive roles and mechanisms of these multifunctional peptides, we can better appreciate their capacity to prevent and treat vascular aging and associated cardiovascular disorders. Future research should aim to further elucidate their therapeutic effects and optimize their clinical applications.

Keywords:  Mitochondrial-derived peptides; cardiovascular diseases.; endothelial function; oxidative stress; vascular aging

DOI:  https://doi.org/10.2174/011573403X375709250616134726
Antioxidants (Basel). 2025 Jun 18. pii: 753. [Epub ahead of print]14(6):

Impact of a Formulation Containing Chaga Extract, Coenzyme Q10, and Alpha-Lipoic Acid on Mitochondrial Dysfunction and Oxidative Stress: NMR Metabolomic Insights into Cellular Energy.

Maria D'Elia, Carmen Marino, Rita Celano, Enza Napolitano, Chiara Colarusso, Rosalinda Sorrentino, Anna Maria D'Ursi, Luca Rastrelli.

   OBJECTIVES: The aim of this study was to evaluate the impact of a novel antioxidant formulation (RE:PAIR, RP-25) containing CoQ10, alpha-lipoic acid, and Chaga extract on mitochondrial dysfunction and oxidative stress. To explore the activity of the formulation on neuronal cells, we explored cell metabolism and its activity as an antioxidant, using a combination of NMR-based metabolomics and UHPLC-HRMS analytical techniques.
METHODS: SH-SY5Y neuroblastoma cells were treated with RP-25, and cell viability was assessed via CCK-8 assay. Metabolomic profiles of the treated and untreated cells were analyzed by 1D-NMR, providing insights into both intracellular metabolites (endometabolome) and excreted metabolites (exometabolome). Additionally, a UHPLC-HRMS method was developed for quality control and analysis of the RP-25 formulation. Multivariate statistical approaches, including PLS-DA and volcano plot analyses, were used to identify key metabolic changes. Changes in mitochondrial membrane potential were assessed by means of TMRE assay, while radical oxygen species (ROS) were measured by means of the DCHF assay.
RESULTS: RP-25 treatment did not affect cell viability but significantly increased metabolic pathways, including amino acid biosynthesis, oxidative phosphorylation, and glycolysis. Higher levels of ATP, glutamate, tyrosine, and proline were observed in treated cells than in control cells, indicating enhanced cellular energy production, as also proved by the increased stability of the mitochondrial membrane after RP-25 treatment, an index of preserved mitochondrial functions. In support, the formulation RP-25 showed antioxidant activity when cells underwent peroxide oxygen stimulation. This effect was mainly due to the combination of Chaga, CoQ10, and ALA, main components of the RP25 formulation. Moreover, the analysis of enriched pathways highlighted that RP formulation influenced mitochondrial energy and oxidative stress response.
CONCLUSIONS: RP-25 demonstrated biological activity in that it mitigated mitochondrial dysfunction and oxidative stress in neuronal cells, with potential implications in neuronal diseases associated with dysfunctional mitochondria.

Keywords:  1H-NMR metabolomics; Inonotus obliquus; SH-SY5Y cells; UHPLC-HRMS/MS; cellular metabolism; coenzyme Q10; fibromyalgia; lipoic acid; mitochondrial dysfunction; neurotransmission

DOI:  https://doi.org/10.3390/antiox14060753
Ageing Res Rev. 2025 Jun 23. pii: S1568-1637(25)00158-8. [Epub ahead of print]110 102812

Crosstalk between oxidative stress, mitochondrial dysfunction, chromosome instability, and the activation of the cGAS-STING/IFN pathway in systemic sclerosis.

Mohammad Waseem, Azait Imtiaz, Amanda Alexander, Lauren Graham, Rafael Contreras-Galindo.

  Systemic sclerosis (SSc) is an autoimmune disorder characterized by fibrosis, vascular dysfunction, and immune dysregulation. Recent studies have highlighted the crucial role of cellular stress responses and their connection to innate immunity in SSc pathogenesis, particularly the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling pathway, which has emerged as a pivotal mediator. In SSc, cGAS detects cytosolic DNA and activates STING, triggering type I interferon production and proinflammatory responses. Errors in chromosome segregation, leading to chromosomal instability (CIN) and micronucleus formation, are major contributors to cytosolic DNA release. Additionally, mitochondrial dysfunction in response to stress signaling leads to the release of mitochondrial DNA (mtDNA) into the cytoplasm, further enhancing cGAS-STING activation, although this mechanism requires further validation. Furthermore, mitochondrial impairment leads to excessive production of reactive oxygen species (ROS), which cleave chromosomal DNA and oxidize mtDNA, contributing to chronic inflammation and fibrosis. Alterations in inflammasome and endosome pathways further amplify interleukin and type I interferon responses. This review highlights the crosstalk between mitochondria, ROS, chromosomal missegregation, and the cGAS-STING pathway in SSc pathogenesis. We also discuss emerging therapeutics targeting the cGAS-STING pathway, which hold promise for regulating disease progression and improving outcomes for SSc patients. Although most evidence remains preclinical and long-term outcome data are scarce, this review underscores the potential of emerging therapeutic strategies and emphasizes the importance of personalized approaches. Further research into the molecular signatures of this pathway in SSc could pave the way for precision medicine strategies in the clinical management of this disease.

Keywords:  CGAS, STING; Centromeres; Cytosolic DNA; Fibrosis; IFN-β; IL-6; Inflammation; Mitochondria; MtDNA; Oxidative Stress; ROS; SSc

DOI:  https://doi.org/10.1016/j.arr.2025.102812
Biomarkers. 2025 Jun 21. 1-13

Evaluating Cell-Free Circulatory Mitochondrial DNA as a Comprehensive Biomarker for Stress: Meta-Analysis of Psychological and Physiological Stress Responses.

Arpan Chattopadhyay, Harshita Tak, Hemanth Naick B.

   BACKGROUND: Mitochondria play a crucial role in cellular processes such as energy metabolism, reactive oxygen species (ROS) generation, and apoptosis. Mitochondrial dysfunction induced by stress has been implicated in various health conditions. Circulating cell-free mitochondrial DNA (CFC-MT-DNA) has emerged as a potential biomarker reflecting mitochondrial damage under stress.
METHODS: To evaluate the association between CFC-MT-DNA levels and human stress through a systematic review and meta-analysis of case-control studies. A comprehensive literature search was conducted across PubMed, Web of Science, and ScienceDirect databases up to September 2023. Eight eligible studies assessing CFC-MT-DNA levels in stressed versus control individuals were included. Data were analysed using RevMan 5.4 software.
RESULTS: The meta-analysis revealed significantly elevated CFC-MT-DNA levels in individuals experiencing stress (P = 0.03), particularly in psychological stress-related conditions such as bipolar disorder and major depressive disorder. However, no significant increase was observed in physiological stress conditions, including diabetes and sports training. High heterogeneity (I2 = 96%) was observed across studies.
CONCLUSION: CFC-MT-DNA shows promise as a non-invasive biomarker for psychological stress. Further longitudinal and mechanistic studies are needed to clarify its role across different types of stress and its potential clinical utility.

Keywords:  Biomarkers; CFC-MT-DNA; Copy number; Gene Ontology; Stress

DOI:  https://doi.org/10.1080/1354750X.2025.2522888
Biomedicines. 2025 May 29. pii: 1338. [Epub ahead of print]13(6):

Involvement of Oxidative Stress in Mitochondrial Abnormalities During the Development of Heart Disease.

Naranjan S Dhalla, Petr Ostadal, Paramjit S Tappia.

  Background: Several mitochondrial abnormalities such as defective energy production, depletion of energy stores, Ca2+ accumulation, generation of reactive oxygen species, and impaired intracellular signaling are associated with cardiac dysfunction during the development of different heart diseases. Methods: A narrative review was compiled by a search for applicable literature in MEDLINE via PubMed. Results: Mitochondria generate ATP through the processes of electron transport and oxidative phosphorylation, which is used as energy for cardiac contractile function. Mitochondria, in fact, are the key subcellular organelle for the regulation of intracellular Ca2+ concentration and are considered to serve as a buffer to maintain Ca2+ homeostasis in cardiomyocytes. However, during the development of heart disease, the excessive accumulation of intracellular Ca2+ results in mitochondria Ca2+-overload, which, in turn, impairs mitochondrial energy production and induces cardiac dysfunction. Mitochondria also generate reactive oxygen species (ROS), including superoxide anion radicals and hydroxyl radicals as well as non-radical oxidants such as hydrogen peroxide, which promote lipid peroxidation and the subsequent disturbance of Ca2+ homeostasis, cellular damage, and death. Conclusion: These observations support the view that both oxidative stress and intracellular Ca2+-overload play a critical role in mitochondrial disruption during the pathogenesis of different cardiac pathologies.

Keywords:  Ca2+-handling defects; cardiac dysfunction; cell death; heart disease; mitochondria; oxidative stress

DOI:  https://doi.org/10.3390/biomedicines13061338
Psychoneuroendocrinology. 2025 Jun 06. pii: S0306-4530(25)00229-X. [Epub ahead of print]179 107506

Saliva and blood cell-free mtDNA reactivity to acute psychosocial stress.

Caroline Trumpff, David Shire, Jeremy Michelson, Natalia Bobba-Alves, Temmie Yu, Richard P Sloan, Robert-Paul Juster, Michio Hirano, Martin Picard.

  Human blood contains cell-free mitochondrial DNA (cf-mtDNA) that dynamically increases in concentration in response to acute mental stress. Like other neuroendocrine stress markers, we previously found that cf-mtDNA is also detectable in saliva, calling for studies examining saliva cf-mtDNA reactivity to mental stress. In the present study, participants from the MiSBIE (Mitochondrial Stress, Brain Imaging, and Epigenetics) study (n = 68, 66 % women), were exposed to a brief socio-evaluative stressor, which induced a striking 280 % or 2.8-fold increase in saliva cf-mtDNA concentration within 10 min (g=0.55, p < 0.0001). In blood drawn concurrently with saliva sampling, stress increased cf-mtDNA by an average 32 % at 60 min in serum (g=0.20), but not in anticoagulated plasma where cf-mtDNA decreased by 19 % at 60 min (g=0.25). Examining the influence of mitochondrial health on cf-mtDNA reactivity in participants with rare mitochondrial diseases (MitoD), we report that a subset of MitoD participants exhibit markedly blunted saliva cf-mtDNA stress reactivity, suggesting that bioenergetic defects within mitochondria may influence the magnitude of saliva, and possibly blood cf-mtDNA responses. Our results document robust saliva cf-mtDNA stress reactivity and provide a methodology to examine the psychobiological regulation of cell-free mitochondria in future studies.

Keywords:  Acute psychological stress; Cell-free mitochondrial DNA (cf-mtDNA); Energy; Mitochondrion; Repeated measures; Saliva

DOI:  https://doi.org/10.1016/j.psyneuen.2025.107506
Front Pharmacol. 2025 ;16 1593264

Neuroprotective potential of quercetin in Alzheimer's disease: targeting oxidative stress, mitochondrial dysfunction, and amyloid-β aggregation.

Mohd Adnan, Arif Jamal Siddiqui, Fevzi Bardakci, Malvi Surti, Riadh Badraoui, Mitesh Patel.

   Introduction: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-beta (Aβ) peptide accumulation, oxidative stress, mitochondrial dysfunction and cholinergic deficits, all of which contribute to neuronal damage and cognitive decline.
Methods: This study investigated the neuroprotective potential of quercetin, a natural flavonoid, in human neuroblastoma SH-SY5Y cells exposed to Aβ-induced toxicity. Various assays were conducted to evaluate cell viability, reactive oxygen species (ROS) levels, mitochondrial membrane potential (ΔΨm), acetylcholinesterase (AChE) activity and Aβ aggregation.
Results: Quercetin significantly enhanced cell viability and reduced oxidative stress by lowering intracellular ROS levels. It preserved mitochondrial integrity by stabilizing ΔΨm and inhibited AChE activity, thereby supporting cholinergic function. Additionally, quercetin reduced Aβ aggregation and the formation of toxic amyloid fibrils.
Discussion: These findings suggest that quercetin confers neuroprotection by targeting multiple pathological mechanisms involved in AD, including oxidative stress, mitochondrial dysfunction, AChE activity and Aβ aggregation. Quercetin demonstrates promise as a natural therapeutic agent for the treatment of AD. However, further in-vivo investigations and clinical studies are warranted to validate these findings and explore its translational potential.

Keywords:  Alzheimer’s disease; Aβ aggregation; SH-SY5Y cells; amyloid-beta; neuroprotection; oxidative stress; quercetin

DOI:  https://doi.org/10.3389/fphar.2025.1593264
Environ Pollut. 2025 Jun 21. pii: S0269-7491(25)01068-1. [Epub ahead of print]382 126695

Environmental nanoplastics induce mitochondrial dysfunction: A review of cellular mechanisms and associated diseases.

Huanpeng Liu, Huiqi Li, Xinxin Yao, Xiaoqing Yan, Renyi Peng.

  As microplastics (MPs) with smaller particle sizes, nanoplastics (NPs) are widespread in the environment and are characterized by high mobility, a large specific surface area, and a high capacity for adsorption. These properties have made NPs a focal point of global research. NPs have been detected in various biological organisms, including humans, where they can enter cells through biological membranes and even penetrate subcellular structures such as mitochondria and lysosomes, leading to cytotoxicity. This review systematically summarizes the latest research progress of NP-induced mitochondrial damage and its pathophysiological consequences. The key findings revealed that nanoparticles penetrate the biological barrier through endocytosis and membrane fusion, accumulate in the mitochondrial matrix, and trigger cristal deformation, fission fusion imbalance, and membrane depolarization there. Mechanistic studies have shown that NP exposure can disrupt electron transport chain complex activity loss, induce reactive oxygen species (ROS) overproduction, and alter calcium homeostasis. Furthermore, we summarize the various diseases-such as neurodegenerative disorders, diabetes, cardiovascular diseases, and reproductive toxicity-that are linked to NP exposure. Finally, we address the current challenges and future prospects in NP research. This study provides mechanistic insights for the development of mitochondrial targeted therapy strategies and informs regulatory policies regarding exposure thresholds for NPs.

Keywords:  Diseases; Mitochondrial dysfunction; NPs; Programmed cell death

DOI:  https://doi.org/10.1016/j.envpol.2025.126695
Pak J Pharm Sci. 2025 May-Jun;38(3):38(3): 841-852

Mitophagy as a therapeutic target for myocardial fibrosis: Mechanistic insights and potential pharmacological interventions.

Jie Wu, Tingjuan Mei, Yang Dong, Fen Zhang, Xingxing Li, Lei Wang.

Myocardial fibrosis is a central pathological feature of various cardiovascular diseases, including heart failure and hypertension. It involves the activation of cardiac fibroblasts, transforming them into myofibroblasts that secrete pro-fibrotic factors, leading to excessive extracellular matrix deposition and progressive cardiac dysfunction. Mitochondrial dysfunction plays a critical role in the development of myocardial fibrosis, with mitophagy, a selective form of autophagy, essential for maintaining mitochondrial quality by removing damaged mitochondria. This process is vital in mitigating fibrosis progression. Recent studies suggest that pharmacological modulation of mitophagy may offer novel therapeutic strategies for cardiovascular diseases involving fibrosis. This review explores the mechanisms of mitophagy in myocardial fibrosis, highlighting key proteins and molecular pathways involved in fibroblast activation and mitochondrial dysfunction. Additionally, it discusses the therapeutic potential of targeting mitophagy to mitigate myocardial fibrosis, emphasizing the importance of balancing mitophagy modulation. Overall, targeting mitophagy pathways holds promise as a therapeutic approach for managing myocardial fibrosis and improving heart function.
Adv Biol (Weinh). 2025 Jun 25. e00110

Lithocholic Acid, Calorie Restriction, and Halting Aging.

Cade Ward, Michael M Shahid, Grace Hohman, Mohamed A Eldeeb.

  While aging is a natural biological process, it is associated with a greater risk for multiple diseases, including cancer, neurodegeneration, and cardiovascular disease. Thus, it is important to study the biochemical mechanisms involved in aging to understand how to treat and prevent these health conditions. The discovery that calorie restriction (CR) promoted longevity in various organisms is a major breakthrough for aging research. Molecular studies of CR have revealed that it mediates its anti-aging effects by activating key signaling pathways, including the AMPK pathway. This pathway is important for regulating various processes, including energy homeostasis, metabolism, and proteostasis. Despite the advantages associated with CR, this practice can have detrimental effects, including decreased liver, body, and muscle mass. Additionally, CR is difficult to track and maintain, limiting its long-term potential. Interestingly, direct activation of the AMPK pathway offers a potential approach to increase longevity and quality of life without dietary restrictions. Remarkably, a recent discovery revealed that lithocholic acid (LCA), a metabolite from bile acid, could directly activate the AMPK pathway. Activation of the AMPK pathway by LCA leads to the beneficial effects of CR without the negative effects. These recent findings point to the possibility that supplementation of specific doses of LCA could offer a novel approach to induce anti-aging pathways that lead to increased longevity and improved quality of life.

Keywords:  AMPK; aging; calorie restriction; cell signaling; neurodegeneration; protein degradation

DOI:  https://doi.org/10.1002/adbi.202500110
Biogerontology. 2025 Jun 25. 26(4): 128

Mechanisms of endothelial senescence and vascular aging.

Qiao Li, Zonghao Qian, Yuzhen Huang, Xiao Yang, Jiankun Yang, Nanyin Xiao, Guangyu Liang, Heng Zhang, Yanguang Fu, Yan Lin, Cuntai Zhang, Anding Liu.

   SCOPE: Cardiovascular disease (CVD) is a major cause of mortality, especially in the aging population. Aging is one of the main risk factors contributing to CVD, leading to early mortality and a decline in the quality of life. Vascular aging is closely linked with atherosclerosis, diabetes, hypertension, stroke, heart failure, and peripheral arterial diseases. Elucidating the cellular and molecular mechanisms underlying vascular aging help to develop therapeutic strategies that can address age-related vascular diseases and decrease the rate of morbidity and mortality among the older population. Endothelial cells located on the interior layer of blood vessels. Intima layers of vascular vessels are damaged and remodeled during vascular aging. The dysfunction of smooth muscle cells and endothelial cells plays key roles in vascular aging. Common pathological changes during vascular aging include arterial stiffness, calcification, and atherosclerosis. Endothelial cell senescence is driven by complex underlying mechanisms. The complex regulation of aging and antiaging network in endothelial cells involve several factors, such as Klotho protein, nitric oxide, fibroblast growth factor 21 (FGF21), and SIRT family members.
OBJECTIVES: This review aims to systematically delineate the mechanisms underlying the endothelial senescence.
METHODOLOGY: The publications on the endothelial cell senescence mechanisms and its roles in vascular aging and aging related diseases are comprehensively investigated and summarized. In this review, the roles of various components in endothelial cell senescence are discussed to elucidate the underlying molecular mechanisms of endothelial cell senescence and identify potential therapeutic targets.

Keywords:  Autophagy; Endothelial senescence; Inflammation; Mitochondria; ROS; Vascular aging

DOI:  https://doi.org/10.1007/s10522-025-10279-y
Atheroscler Plus. 2025 Sep;61 1-11

The role and mechanism of PGC-1α in oxLDL-induced ferroptosis of vascular endothelial cells.

Jiao Li, Pingping He, Yu Zhang, Ranzun Zhao, Changyin Shen, Chaofu Li, Weiwei Liu, Zhijiang Liu, Xianping Long, Yan Wang, Bei Shi.

Ferroptosis is a regulated form of cell death that is dependent on reactive oxygen species (ROS) and iron metabolism. Ferroptosis can participate in the formation and rupture of atherosclerotic plaque by regulating apoptosis. However, the mechanism of vascular endothelial cells (VECs) ferroptosis in the occurrence and development of atherosclerosis (AS) requires further exploration. Previous studies have shown that peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) can improve mitochondrial dysfunction and apoptosis induced by oxidized low-density lipoprotein (oxLDL), but its specific role in VECs ferroptosis remains unclear. In this study, we found that oxLDL can induce VECs ferroptosis, and mitochondria are key to oxLDL-induced VECs ferroptosis. As a key regulator of mitochondrial function, the protein expression of PGC-1α was lower in oxLDL-treated VECs. Moreover, overexpression of PGC-1α inhibited oxLDL-induced VECs ferroptosis, whereas the role of PGC-1α was affected by its upstream regulatory molecule AMPK in this process. This study explores the new idea of oxLDL-induced VECs ferroptosis mediated by AMPK/PGC-1α to better understand the pathogenesis of vascular lesions caused by high lipid levels and provides a theoretical basis for the early prevention of AS.

DOI: https://doi.org/10.1016/j.athplu.2025.05.002
Eur J Pharmacol. 2025 Jun 20. pii: S0014-2999(25)00624-7. [Epub ahead of print] 177870

Chlorogenic acid mitigates DHEA-induced oxidative stress in granulosa cells and alleviates ferroptosis via the NF-κB signaling pathway in PCOS.

Yi Lin, Yahui Zhang, Xiaoying Ding, Huanbai Xu, Chuanhao Xiong, Min Tang, Yongde Peng.

  Polycystic ovary syndrome (PCOS) is a common endocrine disorder, and the effects of chlorogenic acid (CA) on it are unclear. This study investigated CA's therapeutic effects and mechanisms on a dehydroepiandrosterone (DHEA)-induced PCOS rat model and KGN granulosa cells, hypothesizing that CA ameliorates hormonal imbalance, inflammation, and oxidative stress in PCOS by regulating the NF - κB signaling pathway and ferroptosis - related proteins. The methods included in - vivo experiments on rats with different treatments and in - vitro experiments on KGN cells. Results showed that CA restored the estrous cycle and ovulation, alleviated hyperandrogenism, reduced inflammation and oxidative stress markers, improved follicular development, and decreased ferroptosis in PCOS rats. It upregulated GPX4 and SLC7A11 expression, decreased ROS levels, and bound strongly with NF - κB p65, downregulating NF - κB pathway activation markers. In KGN cells, CA improved proliferation, reduced ferroptosis, oxidative stress, and mitochondrial damage, similar to Fer - 1. The combined use of an NF - κB inhibitor and CA restored the cellular oxidative state. In conclusion, CA improves hormonal balance, alleviates inflammation and oxidative stress by regulating the NF - κB pathway and ferroptosis - related proteins, showing potential as a PCOS therapeutic agent, and further studies are needed for confirmation and clinical application exploration.

Keywords:  Chlorogenic Acid; Ferroptosis; Inflammation; NF-κB Pathway; Polycystic Ovary Syndrome

DOI:  https://doi.org/10.1016/j.ejphar.2025.177870
Vet Microbiol. 2025 Jun 23. pii: S0378-1135(25)00251-2. [Epub ahead of print]307 110616

Honokiol rescues progranulin deficiency in pathogen-induced and genetically driven neurodegeneration: Bridging veterinary models with therapeutic development.

Zezhao Cao, Wenqi He, Ruijie Hu, Yuzhu Chen, Jun Xue, Feng Gao, Yungang Lan.

  Progranulin (PGRN), a crucial regulator of lysosomal function, is deficient in several neurodegenerative disorders. Restoring PGRN levels with small molecules presents a promising therapeutic strategy for these conditions. Honokiol (HNK), a polyphenolic compound known for its neuroprotective effects, has demonstrated potential in various neurodegenerative diseases (ND), though its precise mechanisms remain unclear. This study explores HNK's ability to upregulate PGRN expression in nerve cells and central nervous system tissues. Our results show that HNK enhances PGRN expression and lysosomal targeting in nerve cells, rescues PGRN deficiency in PHEV-infected models both in vitro and in vivo, and significantly increases brain PGRN levels in GRN haploinsufficient mice following oral administration. Collectively, these findings establish HNK's multimodal action as a promising therapeutic intervention for neurodegenerative conditions spanning both infectious (PHEV-mediated) and genetic (GRN-linked) etiologies of PGRN deficiency.

Keywords:  GRN haploinsufficient model; HNK; ND; PGRN; PHEV-infected model

DOI:  https://doi.org/10.1016/j.vetmic.2025.110616