bims-mistre 2025-03-09 papers

bims-mistre

Biomed News

on Mito stress

Issue of 2025–03–09
fifteen papers selected by
Ellen Siobhan Mitchell, MitoQ

Oxidative stress in endometriosis: Sources, mechanisms and therapeutic potential of antioxidants (Review).
Update on the Role of Cellular Redox System in Health and Illness.
Mitochondrial Dysfunction in Alzheimer's Disease.
The Peripheral Amyloid-β Nexus: Connecting Alzheimer's Disease with Atherosclerosis through Shared Pathophysiological Mechanisms.
Therapeutic assessment of a novel mitochondrial complex I inhibitor in in vitro and in vivo models of Alzheimer's disease.
Systemic Neuroprotection by Chlorogenic Acid: Antioxidant and Anti-inflammatory Evaluation in Early Neurodegeneration Induced by 3-Nitropropionic Acid in Mice.
Mitochondria in aging and age-associated diseases.
Interspecies differences in mitochondria: Implications for cardiac and vascular translational research.
A systematic review of the therapeutic potential of nicotinamide adenine dinucleotide precursors for cognitive diseases in preclinical rodent models.
Anti-inflammatory and antioxidant effects of anthocyanins in Nonalcoholic fatty liver disease (NAFLD): a systematic review of in vivo studies.
The effect of mitochondrial-associated endoplasmic reticulum membranes (MAMs) modulation: New insights into therapeutic targets for depression.
Mitochondrial accumulation and lysosomal dysfunction result in mitochondrial plaques in Alzheimer's disease.
Mitochondria at the crossroads: Quality control mechanisms in neuronal senescence and neurodegeneration.
Macrophage A2aR Alleviates LPS-Induced Vascular Endothelial Injury and Inflammation via Inhibiting M1 Polarisation and Oxidative Stress.
Impacts of Curcumin Supplementation on Cardiometabolic Risk Factors in Patients With Polycystic Ovary Syndrome: A Systematic Review and Dose-Response Meta-Analysis.

Int J Mol Med. 2025 May;pii: 72. [Epub ahead of print]55(5):

Oxidative stress in endometriosis: Sources, mechanisms and therapeutic potential of antioxidants (Review).

Li Huang, Ling Shi, Maoya Li, Xiaolan Yin, Xiaoli Ji.

  Endometriosis affects ~15% of women of reproductive age worldwide, impacting ~190 million individuals. Despite its high prevalence, the precise pathogenesis of endometriosis remains unclear. Emerging evidence has highlighted oxidative stress as a pivotal factor in the initiation and progression of this disease. The present review comprehensively summarizes the sources of oxidative stress in endometriosis, including redox imbalance characterized by increased oxidative markers and diminished antioxidant defenses, mitochondrial dysfunction leading to excessive production of reactive oxygen species (ROS), and aberrant iron metabolism that further amplifies ROS generation. The accumulation of ROS disrupts cellular redox homeostasis, thereby exacerbating oxidative stress and activating key cell proliferation signaling pathways, such as the Raf/MEK/ERK and mTOR pathways. Activation of these pathways promotes the survival and proliferation of ectopic endometrial cells, contributing to lesion development and disease progression. The present review also discusses how oxidative stress induces epigenetic modifications that may further drive the pathological features of endometriosis. Finally, the recent advances in the application of antioxidants as therapeutic agents for endometriosis are highlighted, underscoring their potential to mitigate oxidative stress and ameliorate disease symptoms. Understanding the intricate relationship between oxidative stress and endometriosis may pave the way for novel diagnostic and therapeutic strategies aimed at improving patient outcomes.

Keywords:  antioxidant therapy; endometriosis; oxidative stress; reactive oxygen species

DOI:  https://doi.org/10.3892/ijmm.2025.5513
Curr Drug Discov Technol. 2025 Mar 03.

Update on the Role of Cellular Redox System in Health and Illness.

Manvi Karayat, Kalpana Rahate, Shristi Singh.

  An imbalance between Reactive Oxygen Species (ROS) and antioxidants in the circulatory system leads to oxidative stress, which has been linked to several pathological conditions, including cancer, aging, and neurological and cardiovascular diseases. Antioxidants play a crucial role in re-ducing oxidative damage by neutralizing harmful free radicals and preventing cellular injury. The processes generating cellular oxidative stress and the curative effects of antioxidants, the origins and effects of reactive oxygen species (ROS), the role that oxidative stress plays in the pathogenesis of disease, and the several kinds of antioxidants-including enzymatic and non-enzymatic antioxidants are thoroughly explored in this review. We also emphasized the medicinal uses of antioxidants, both natural and synthetic, in the prevention and treatment of disorders associated with oxidative stress. Furthermore, we discussed the challenges and potential paths ahead for antioxidant research, such as developing new antioxidant molecules with higher efficacy and improving antioxidant delivery sys-tems. This study provides information regarding the complicated dynamics of oxidative stress and the potential benefits of antioxidants for preserving cellular homeostasis and advancing human health.

Keywords:  Antioxidant; ROS; enzymatic antioxidants; human health; nonenzymatic antioxidants; oxidation stress

DOI:  https://doi.org/10.2174/0115701638349511250121114323
Ageing Res Rev. 2025 Feb 27. pii: S1568-1637(25)00059-5. [Epub ahead of print] 102713

Mitochondrial Dysfunction in Alzheimer's Disease.

Maria Clara Bila D'alessandro, Salim Kanaan, Mauro Geller, Domenico Praticò, João Paulo Lima Daher.

  Alzheimer's disease (AD) is a chronic neurodegenerative disease characterized by progressive cognitive decline and distinct neuropathological features. The absence of a definitive cure presents a significant challenge in neurology and neuroscience. Early clinical manifestations, such as memory retrieval deficits and apathy, underscore the need for a deeper understanding of the disease's underlying mechanisms. While amyloid-β plaques and tau neurofibrillary tangles have dominated research efforts, accumulating evidence highlights mitochondrial dysfunction as a central factor in AD pathogenesis. Mitochondria, essential cellular organelles responsible for energy production necessary for neuronal function become impaired in AD, triggering several cellular consequences. Factors such as oxidative stress, disturbances in energy metabolism, failures in the mitochondrial quality control system, and dysregulation of calcium release are associated with mitochondrial dysfunction. These abnormalities are closely linked to the neurodegenerative processes driving AD development and progression. This review explores the intricate relationship between mitochondrial dysfunction and AD pathogenesis, emphasizing its role in disease onset and progression, while also considering its potential as a biomarker and a therapeutic target.

Keywords:  Mitochondrial dysfunction. Alzheimer’ disease. Pathology. Mitophagy. Neurodegeneration

DOI:  https://doi.org/10.1016/j.arr.2025.102713
Neuromolecular Med. 2025 Mar 03. 27(1): 20

The Peripheral Amyloid-β Nexus: Connecting Alzheimer's Disease with Atherosclerosis through Shared Pathophysiological Mechanisms.

Manal M Khowdiary, Hayder M Al-Kuraishy, Ali I Al-Gareeb, Ali K Albuhadily, Ahmed A Elhenawy, Eman K Rashwan, Athanasios Alexiou, Marios Papadakis, Mohammed E Abo-El Fetoh, Gaber El-Saber Batiha.

  Alzheimer's disease (AD) and atherosclerosis (AS) are two chronic diseases with seemingly distinct pathologies. However, emerging research points to a bidirectional relationship driven by common mechanisms, such as inflammation, oxidative stress, and dysregulation of Amyloid-Beta (Aβ). This review focuses on the role of Aβ as a critical molecular link between AD and AS, emphasizing its contribution to neuronal impairment and vascular damage. Specifically, peripheral Aβ produced in the pancreas and skeletal muscle tissues exacerbates AS by promoting endothelial dysfunction and insulin resistance (IR). Furthermore, AS accelerates AD progression by impairing cerebral blood flow and inducing chronic hypoxia, causing Aβ accumulation. This review critically evaluates recent findings, highlighting inconsistencies in clinical studies and suggesting future research directions. Understanding the bidirectional influence of AD and AS could pave the way for novel therapeutic approaches targeting shared molecular pathways, particularly emphasizing Aβ clearance and inflammation.

Keywords:  Alzheimer's disease; Amyloid-beta (Aβ); Atherosclerosis; Aβ clearance pathways; Insulin resistance; Neuroinflammation; Oxidative stress; Vascular dysfunction

DOI:  https://doi.org/10.1007/s12017-025-08836-2
bioRxiv. 2025 Feb 17. pii: 2025.02.12.637918. [Epub ahead of print]

Therapeutic assessment of a novel mitochondrial complex I inhibitor in in vitro and in vivo models of Alzheimer's disease.

Sergey Trushin, Thi Kim Oanh Nguyen, Andrea Stojacovic, Mark Ostroot, J Trey Deason, Su-Youne Chang, Liang Zhang, Slobodan I Macura, Toshihiko Nambara, Wenyan Lu, Takahisa Kanekiyo, Eugenia Trushina.

Despite recent approval of monoclonal antibodies that reduce amyloid (Aβ) accumulation, the development of disease-modifying strategies targeting the underlying mechanisms of Alzheimer's disease (AD) is urgently needed. We demonstrate that mitochondrial complex I (mtCI) represents a druggable target, where its weak inhibition activates neuroprotective signaling, benefiting AD mouse models with Aβ and p-Tau pathologies. Rational design and structure‒activity relationship studies yielded novel mtCI inhibitors profiled in a drug discovery funnel designed to address their safety, selectivity, and efficacy. The new lead compound C458 is highly protective against Aβ toxicity, has favorable pharmacokinetics, and has minimal off-target effects. C458 exhibited excellent brain penetrance, activating neuroprotective pathways with a single dose. Preclinical studies in APP/PS1 mice were conducted via functional tests, metabolic assessment, in vivo 31 P- NMR spectroscopy, blood cytokine panels, ex vivo electrophysiology, and Western blotting. Chronic oral administration improved long-term potentiation, reduced oxidative stress and inflammation, and enhanced mitochondrial biogenesis, antioxidant signaling, and cellular energetics. These studies provide further evidence that the restoration of mitochondrial function and brain energetics in response to mild energetic stress represents a promising disease- modifying strategy for AD.

DOI: https://doi.org/10.1101/2025.02.12.637918
Neurochem Res. 2025 Mar 04. 50(2): 113

Systemic Neuroprotection by Chlorogenic Acid: Antioxidant and Anti-inflammatory Evaluation in Early Neurodegeneration Induced by 3-Nitropropionic Acid in Mice.

Angélica Cantero-Téllez, Leticia Moreno-Fierros, Gabriel Gutiérrez-Ospina, Ana Cecilia Santiago-Prieto, Imelda Juárez, Miriam Rodríguez-Sosa, Elizabeth Hernández-Echeagaray.

  Neurodegeneration is characterized by the progressive loss of neurons commonly attributed to neurological causes. Studies published over the past two decades suggest that neurodegeneration may occur due to systemic diseases that compromise energy metabolism throughout the body. This metabolic imbalance develops over decades before neurodegeneration is clinically documented or inferred. It is now accepted that long-lasting oxidative stress and inflammation link neurodegeneration with altered energy metabolism in the body. Systemic prevention of these factors may reduce the odds of developing neurodegeneration and delay or prevent its progression as individuals age. Chlorogenic acid (CGA) is a polyphenol prevalent in fruits and vegetables that exhibits antioxidant and anti-inflammatory properties. It may serve as a systemic neuroprotectant when consumed regularly before the onset of neurodegeneration. To test this possibility, an experimental model of striatal early neurodegeneration induced by systemic administration of 3-nitropropionic acid (3-NP) was used. This toxin inhibits succinate dehydrogenase (SDH), disrupts electron flow and leads to increased production of reactive oxygen species (ROS) and a pro-inflammatory environment. The severity of symptoms induced by 3-NP varies depending on dosage, duration of exposure and administration route. In the brain, 3-NP affects striatal medium spiny neurons in the basal ganglia and in less degree pyramidal neurons from frontal cortex, a feature observed in Huntington's disease (HD). The aim of this study was to investigate the antioxidant and anti-inflammatory properties of CGA in the 3-NP-induced model of early neurodegeneration. Systemic administration of CGA significantly reduced lipid peroxidation and promoted an anti-inflammatory profile in the brain when co-administered with 3-NP. These results support that CGA could serve as a systemic neuroprotectant in individuals challenged by environmental toxins that disrupt mitochondrial function.

Keywords:  Basal ganglia; Environmental toxins; Huntington’s disease; Lipid peroxidation; Mitochondrial dysfunction; Neuroprotection; Polyphenols

DOI:  https://doi.org/10.1007/s11064-025-04356-4
Mitochondrion. 2025 Feb 27. pii: S1567-7249(25)00019-4. [Epub ahead of print]82 102022

Mitochondria in aging and age-associated diseases.

Sonu Pahal, Nirjal Mainali, Meenakshisundaram Balasubramaniam, Robert J Shmookler Reis, Srinivas Ayyadevara.

Mitochondria, essential for cellular energy, are crucial in neurodegenerative disorders (NDDs) and their age-related progression. This review highlights mitochondrial dynamics, mitovesicles, homeostasis, and organelle communication. We examine mitochondrial impacts from aging and NDDs, focusing on protein aggregation and dysfunction. Prospective therapeutic approaches include enhancing mitophagy, improving respiratory chain function, maintaining calcium and lipid balance, using microRNAs, and mitochondrial transfer to protect function. These strategies underscore the crucial role of mitochondrial health in neuronal survival and cognitive functions, offering new therapeutic opportunities.

DOI: https://doi.org/10.1016/j.mito.2025.102022
Vascul Pharmacol. 2025 Mar 02. pii: S1537-1891(25)00015-1. [Epub ahead of print] 107476

Interspecies differences in mitochondria: Implications for cardiac and vascular translational research.

Lisa Alibrandi, Vincenzo Lionetti.

  Mitochondria are essential organelles that regulate cellular energy metabolism, redox balance, and signaling pathways related to proliferation, aging and survival. So far, significant interspecies differences exist in mitochondrial structure, function, and dynamics, which have critical implications for cardiovascular physiology and pharmacology. This review explores the main differences in mitochondrial properties across species of animals that are commonly used for translational research, emphasizing their cardiac and vascular relevance. By addressing key interspecies differences, including mitochondrial DNA (mtDNA) variation, bioenergetic profile, oxidative stress response, epigenetic regulation, mitochondrial biogenesis, and adaptive mechanisms, we aim to provide insights into the challenges and opportunities in translating preclinical findings to clinical applications. Understanding these interspecies differences is essential for optimizing the design and interpretation of preclinical studies and for developing effective mitochondrial-targeted therapies.

Keywords:  Animal model; Cardiovascular; Epigenetics; Heart; Interspecies variability; Mitochondria; Reactive oxygen species

DOI:  https://doi.org/10.1016/j.vph.2025.107476
BMC Neurosci. 2025 Mar 03. 26(1): 17

A systematic review of the therapeutic potential of nicotinamide adenine dinucleotide precursors for cognitive diseases in preclinical rodent models.

Musaab Abdulrazzaq Qader, Leila Hosseini, Nasrin Abolhasanpour, Farnaz Oghbaei, Leila Maghsoumi-Norouzabad, Hanieh Salehi-Pourmehr, Fatemeh Fattahi, Reza Naghdi Sadeh.

  This systematic review sought to assess the impact of nicotinamide adenine dinucleotide (NAD+) precursors on cognitive impairments in several diseases in rat/mouse models. Accumulating evidence suggests that inflammation, apoptosis, oxidative stress responses, and mitochondrial dysfunction are potential factors of cognitive deficits in aging, Alzheimer's disease (AD), diabetes, traumatic brain injury (TBI), vascular dementia (VAD), and schizophrenia. NAD+ precursors have received increased interest due to their unique molecular structure targets antioxidant and inflammatory pathways and mitochondrial function. The PubMed, Scopus, Google Scholar, Embase, and Web of Science databases were searched through May 30, 2024. Studies investigating the effect of NAD+ precursors on cognitive impairments in rodent models were included. Two reviewers independently extracted and evaluated the data. The PRISMA guidelines for reporting systematic reviews were followed. Thirty preclinical studies were included in the review. Studies have revealed that treatment with NAD+ rescues cognitive deficits by inhibiting inflammation, oxidative stress, and apoptosis and improving mitochondrial function. Preclinical evidence has demonstrated that treatment with NAD+ precursors may be more effective in learning and memory recovery in AD, TBI, diabetes, aging, VAD, and schizophrenia. The outcomes of this investigation may lead to additional studies on the use of NAD+ precursors for treating human cognitive decline.

Keywords:  Cognitive impairment; Inflammation; Memory; Mitochondrial dysfunction; Nicotinamide; Oxidative stress

DOI:  https://doi.org/10.1186/s12868-025-00937-9
Crit Rev Food Sci Nutr. 2025 Mar 05. 1-18

Anti-inflammatory and antioxidant effects of anthocyanins in Nonalcoholic fatty liver disease (NAFLD): a systematic review of in vivo studies.

Kelly Aparecida Dias, Lívya Alves Oliveira, Stephanie Michelin Santana Pereira, Lívia Carvalho Sette Abrantes, Laura Célia Oliveira de Souza Vicente, Reggiani Vilela Gonçalves, Ceres Mattos Della Lucia.

  Anthocyanins are natural flavonoids, which belong to a group of polyphenols with antioxidant, anti-inflammatory, hypolipidemic and hepatoprotective activities. The aim of this systematic review is to answer the questions "What are the impacts of anthocyanins on inflammatory and oxidative mediators of NAFLD in vivo?" and "What are the possible molecular mechanisms involved in the effects of anthocyanins on NAFLD and hepatic steatosis?" The search was performed at PubMed, Scopus, Web of Science, and Embase databases, and the risk of bias was assessed by the SYRCLE tool. The data analysis was conducted following the PRISMA guidelines. Twenty-three studies performed in animal models evaluating the effects of anthocyanins in inflammatory and oxidative stress mediators in NAFLD were included and evaluated. The anthocyanins demonstrated potential positive effects on inflammation and oxidative stress (OS), in addition to reduced hepatic steatosis. The main results identified were a reduction in TLR, NF-κB, MCP-1/CCL-2, TNF-α, IL-6, and IL-1β in addition to an improvement in antioxidant defense with an increase in Nrf2, SOD, GSH, GPx and CAT and a reduction in OS. The findings from this review provide insights for the development of future studies with anthocyanins on liver health and inflammatory and oxidative parameters. PROSPERO (CRD42024502710).

Keywords:  Polyphenols; hepatic steatosis; inflammation; nutraceuticals; oxidative stress

DOI:  https://doi.org/10.1080/10408398.2025.2472882
Neurosci Biobehav Rev. 2025 Mar 01. pii: S0149-7634(25)00087-9. [Epub ahead of print]172 106087

The effect of mitochondrial-associated endoplasmic reticulum membranes (MAMs) modulation: New insights into therapeutic targets for depression.

Maohui Yang, Xuemei Qin, Xiaojie Liu.

  Depression is a prevalent mental disorder with high morbidity and mortality and its pathogenesis remains exactly unclarified. However, mitochondria and endoplasmic reticulum (ER) are two highly dynamic organelles that perform an indispensable role in the development of depression. Mitochondrial dysfunction and ER stress are recognized as vital pathological hallmarks in depression. The changes of intracellular activities such as mitochondrial dynamics, mitophagy, energy metabolism and ER stress are closely correlated with the progression of depression. Moreover, organelles interactions are conducive to homeostasis and cellular functions, and mitochondrial-associated endoplasmic reticulum membranes (MAMs) serve as signaling hubs of the two organelles and the coupling of the pathological progression. The main roles of MAMs are involved in metabolism, signal transduction, lipid transport, and maintenance of its structure and function. At present, accumulating studies elucidated that MAMs have gradually become a novel therapeutic target in treatment of depression. In the review, we focus on influence of mitochondria dysfunction and ER stress on depression. Furthermore, we discuss the underlying role of MAMs in depression and highlight natural products targeting MAMs as potential antidepressants to treat depression.

Keywords:  Depression; Endoplasmic reticulum; MAMs; Membranes couplings; Mitochondria; Natural products

DOI:  https://doi.org/10.1016/j.neubiorev.2025.106087
bioRxiv. 2025 Feb 20. pii: 2025.02.19.639081. [Epub ahead of print]

Mitochondrial accumulation and lysosomal dysfunction result in mitochondrial plaques in Alzheimer's disease.

Xiuli Dan, Deborah L Croteau, Wenlong Liu, Xixia Chu, Paul D Robbins, Vilhelm A Bohr.

Dysfunctional mitophagy is a key component of Alzheimer's disease (AD) pathology, yet direct in vivo evidence and mechanistic insights remain limited. Using a mitophagy reporter in an AD mouse model ( APP / PSEN1 /mt-Keima), we identified mitochondrial plaques (MPs) composed of accumulated mitochondria within or outside lysosomes in AD, but not normal mouse brains. Similar structures were also found in AD human brains, but not in healthy controls. Abnormal mitochondrial accumulation in dystrophic neurites, defective mitophagy, and impaired lysosomal function disrupted proper mitochondrial degradation, resulting in excessive mitochondria accumulation both within and outside autophagic vesicles. The resulting intensive mitochondria-containing neurites coalesce into MPs, which co-develop with amyloid plaques to form mixed plaques. These findings establish MPs as novel pathological entity and a promising therapeutic target in AD.

DOI: https://doi.org/10.1101/2025.02.19.639081
Neurobiol Dis. 2025 Mar 04. pii: S0969-9961(25)00078-6. [Epub ahead of print] 106862

Mitochondria at the crossroads: Quality control mechanisms in neuronal senescence and neurodegeneration.

Yifei Zheng, Jiahui Yang, Xuanyao Li, Linjie Qi, Zhuo Zheng, Jiming Kong, Guohui Zhang, Ying Guo.

  Mitochondria play a central role in essential cellular processes, including energy metabolism, biosynthesis of metabolic substances, calcium ion storage, and regulation of cell death. Maintaining mitochondrial quality control is critical for preserving mitochondrial health and ensuring cellular function. Given their high energy demands, neurons depend on effective mitochondrial quality control to sustain their health and functionality. Neuronal senescence, characterized by a progressive decline in structural integrity and function, is a hallmark of neurodegenerative diseases. In senescent neurons, abnormal mitochondrial morphology, functional impairments, increased reactive oxygen species production and disrupted quality control mechanisms are frequently observed. Understanding the pathological changes in neuronal structure, exploring the intricate relationship between mitochondrial quality control and neuronal health, and leveraging mitochondrial quality control interventions provide a promising foundation for addressing age-related neurodegenerative diseases. This review highlights key mitochondrial quality control, including biogenesis, dynamics, the ubiquitin-proteasome system, autophagy pathways, mitochondria-derived vesicles, and inter-organelle communication, while discussing their roles in neuronal senescence and potential therapeutic strategies. These insights may pave the way for innovative treatments to mitigate neurodegenerative disorders.

Keywords:  Mitochondrial quality control; Neurodegenerative diseases; Neuron; Senescence; Therapeutic strategies

DOI:  https://doi.org/10.1016/j.nbd.2025.106862
J Cell Mol Med. 2025 Mar;29(5): e70458

Macrophage A2aR Alleviates LPS-Induced Vascular Endothelial Injury and Inflammation via Inhibiting M1 Polarisation and Oxidative Stress.

Yanxiu Li, Tingzhen Chen, Iokfai Cheang, Peiben Liu, Lin Zhao, Xiaoxin He, Yuxi Jin, Mingmin Tang, Zhongqi Zhang, Chengyu Sheng, Zhongwen Zhang, Xiangrong Zuo.

  Vascular inflammation and endothelial dysfunction secondary to unchecked activation of endothelium are key mechanisms underlying sepsis and organ failure. However, the intrinsic processes that mitigate excessive endothelial cell activation remain incompletely understood. To determine the central role of adenosine A2a receptor (A2aR) on macrophages in modulating lipopolysaccharide (LPS)-induced vascular endothelial dysfunction, we constructed macrophage A2aR-conditional knockout (Mac-A2aR KO) mice, and stimulated the mice and macrophages with LPS. A2aR agonist, CGS21680, was administered to these models to further explore its impact. Results showed that knockout of Macrophage A2aR exacerbated LPS-induced vascular permeability, oedema, inflammatory cardiac damage and upregulated expression of intercellular adhesion molecule-1 (ICAM-1) and E-selectin in cardiopulmonary vascular endothelium. Moreover, deletion of A2aR on macrophages also markedly aggravated LPS-induced increases in reactive oxygen species (ROS) and declines in antioxidant enzyme gene mRNA and protein expression levels related to oxidative stress (OS). Furthermore, deficiency of A2aR in bone marrow-derived macrophages (BMDMs) promotes LPS-induced macrophage M1 polarisation and secretion of inflammatory cytokines, especially tumour necrosis factor-alpha (TNF-α). Conversely, the pretreatment with CGS21680 in vivo and in vitro showed corresponding improvement in functions of vascular endothelial dysfunction. These data demonstrate that A2aR in macrophages represents a promising novel therapeutic target for LPS-induced uncontrolled vascular endothelial injury and inflammation potentially through reducing macrophage M1 polarisation and OS and inhibiting the production and release of TNF-α production.

Keywords:  Evans; Evans blue‐conjugated albumin (EBA); adenosine A2a receptor; blue‐conjugated albumin (EBA); endotoxemia; macrophage M1 polarisation; oxidative stress; vascular endothelial injury

DOI:  https://doi.org/10.1111/jcmm.70458
Health Sci Rep. 2025 Mar;8(3): e70525

Impacts of Curcumin Supplementation on Cardiometabolic Risk Factors in Patients With Polycystic Ovary Syndrome: A Systematic Review and Dose-Response Meta-Analysis.

Shooka Mohammadi, Somayeh Ziaei, Mehrnaz Morvaridi, Motahareh Hasani, Elham Mirtaheri, Farnaz Farsi, Sara Ebrahimi, Elnaz Daneshzad, Javad Heshmati.

   Background and Aim: Patients with polycystic ovary syndrome (PCOS) commonly have cardiometabolic risk factors. Oxidative stress (OS) significantly contributes to the development of cardiometabolic diseases. Curcumin (CUR) exhibits antioxidant properties that aid in OS regulation. This systematic review and dose-response meta-analysis of randomized clinical trials (RCTs) evaluated the effects of CUR supplementation on cardiometabolic risk factors in women with PCOS.
Methods: A systematic search across various databases was implemented to identify eligible RCTs published until January 2024. A meta-analysis was conducted employing a random-effects model.
Results: Eight RCTs were included in the meta-analysis. It was indicated that CUR supplementation substantially reduced fasting blood sugar (FBS) (standardized mean difference [SMD]: -0.40 mg/dL, 95% confidence interval [CI]: -0.59, -0.21; p < 0.001), insulin (SMD: -0.32 µU/mL, 95% CI: -0.49, -0.14; p < 0.001), homeostasis model assessment of insulin resistance (HOMA-IR) (SMD: -0.36, 95% CI: -0.54, -0.19; p < 0.001), and total cholesterol (TC) (SMD: -0.34 mg/dL, 95% CI: -0.61, -0.08; p = 0.01). In addition, it substantially increased the quantitative insulin sensitivity check index (QUICKI) (SMD: 0.37, 95% CI: 0.13, 0.61; p < 0.001) in the CUR-treated group compared with the control group. However, CUR did not have significant impacts on body mass index (BMI), body weight, serum levels of follicle-stimulating hormone (FSH), triglycerides (TG), dehydroepiandrosterone (DHEA), high-density lipoprotein (HDL), testosterone, low-density lipoprotein (LDL), and luteinizing hormone (LH).
Conclusion: This study revealed that CUR may have the potential to enhance cardiometabolic health by reducing hyperglycemia, insulin resistance, and serum TC levels in women with PCOS.

Keywords:  cardiometabolic; cardiovascular; curcumin; polycystic ovary syndrome

DOI:  https://doi.org/10.1002/hsr2.70525