bims-mistre 2025-01-12 papers

bims-mistre

Biomed News

on Mito stress

Issue of 2025–01–12
23 papers selected by
Ellen Siobhan Mitchell, MitoQ

Mitochondrial protective potential of fucoxanthin in brain disorders.
Gallic acid alleviates exercise-induced muscle damage by inhibiting mitochondrial oxidative stress and ferroptosis.
Curcumin Modulates Platelet Activation and ROS Production Induced by Amyloid Peptides: New Perspectives in Attenuating Prothrombotic Risk in Alzheimer's Disease Patients.
Role of Oxidative Stress in Blood-Brain Barrier Disruption and Neurodegenerative Diseases.
Senkyunolide I prevent chondrocytes from oxidative stress through Nrf2/HO-1 signaling pathway.
The Roles of Oxidative Stress and Red Blood Cells in the Pathology of the Varicose Vein.
Understanding the Molecular Impact of Physical Exercise on Alzheimer's Disease.
Repurposing Nano Curcumin: Unveiling its Therapeutic Potential in Diabetic Nephropathy.
Idebenone Protects Photoreceptors Impaired by Oxidative Phosphorylation Disorder in Retinal Detachment.
Taurine prevents mitochondrial dysfunction and protects mitochondria from reactive oxygen species and deuterium toxicity.
Anti-neuroinflammatory and Neuroprotective Effects of T-006 on Alzheimer's Disease Models by Modulating TLR4-Mediated MyD88/ NF-κB Signaling.
Mechanisms and Potential Benefits of Neuroprotective Agents in Neurological Health.
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells.
Pterostilbene protects against lipopolysaccharide-induced inflammation and blood-brain barrier disruption in immortalized brain endothelial cell lines in vitro.
Undaria pinnatifida fucoidan extract inhibits activation of the NF-κB signaling pathway by herpes simplex virus type 1 and prevents amyloid-β peptide synthesis in retinal pigment epithelium cells.
Ellagic acid alleviates DSS-induced ulcerative colitis by inhibiting ROS/NLRP3 pathway activation and modulating gut microbiota in mice.
From Plant to Pathway: Molecular Mechanisms of Ruscogenin in Preventing Amyloid-Beta Aggregation through Computational and Experimental Approaches.
MnSOD Mimetics in Therapy: Exploring Their Role in Combating Oxidative Stress-Related Diseases.
Brain insulin resistance mediated cognitive impairment and neurodegeneration: Type-3 diabetes or Alzheimer's Disease.
Oxidative/Nitrosative Stress and Brain Involvement in Sepsis: A Relationship Supported by Immunohistochemistry.
Quercetin Alleviates All-Trans-Retinal-Induced Photoreceptor Apoptosis and Retinal Degeneration by Inhibiting the ER Stress-Related PERK Signaling.
Berberine Inhibits the Disruption of the Blood-Brain Barrier and Glial Cell Activation in a Rat Model of Acute Hepatic Encephalopathy.
Investigation of the anti-aging effects of active components of Artemia franciscana loaded in hyalurosome.

J Nutr Sci. 2024 ;13 e21

Mitochondrial protective potential of fucoxanthin in brain disorders.

Khondoker Adeba Ferdous, Joseph Jansen, Emma Amjad, Eliana Pray, Rebecca Bloch, Alex Benoit, Meredith Callahan, Han-A Park.

  Mitochondrial dysfunction is a common feature of brain disorders. Mitochondria play a central role in oxidative phosphorylation; thus changes in energy metabolism in the brain have been reported in conditions such as Alzheimer's disease, Parkinson's disease, and stroke. In addition, mitochondria regulate cellular responses associated with neuronal damage such as the production of reactive oxygen species (ROS), opening of the mitochondrial permeability transition pore (mPTP), and apoptosis. Therefore, interventions that aim to protect mitochondria may be effective against brain disorders. Fucoxanthin is a marine carotenoid that has recently gained recognition for its neuroprotective properties. However, the cellular mechanisms of fucoxanthin in brain disorders, particularly its role in mitochondrial function, have not been thoroughly discussed. This review summarises the current literature on the effects of fucoxanthin on oxidative stress, neuroinflammation, and apoptosis using in vitro and in vivo models of brain disorders. We further present the potential mechanisms by which fucoxanthin protects mitochondria, with the objective of developing dietary interventions for a spectrum of brain disorders. Although the studies reviewed are predominantly preclinical studies, they provide important insights into understanding the cellular and molecular functions of fucoxanthin in the brain. Future studies investigating the mechanisms of action and the molecular targets of fucoxanthin are warranted to develop translational approaches to brain disorders.

Keywords:  Antioxidant; Brain; Fucoxanthin; Mitochondria

DOI:  https://doi.org/10.1017/jns.2024.16
J Transl Med. 2025 Jan 08. 23(1): 30

Gallic acid alleviates exercise-induced muscle damage by inhibiting mitochondrial oxidative stress and ferroptosis.

Likai Yu, Di Tian, Zishan Su, Li Zhang, Shaobo Guo, Wenhui Zhu, Yuan Fang, Peimin Wang, Nongshan Zhang.

   BACKGROUND: Skeletal muscle injury caused by excessive exercise is one of the most commonly seen clinical diseases. It is indispensable to explore drugs for treating and relieving skeletal muscle injury. Gallic acid (GA) is a polyphenolic extract that has anti-inflammatory and antioxidant biological activities. However, its function and mechanism in skeletal muscle injury remain unclear.
METHODS: We first established a skeletal muscle injury model caused by excessive exercise. Histopathological analysis was used to determine the severity of skeletal muscle injury in mice. Techniques such as ELISA, Western blot, and RT-qPCR were used to measure skeletal muscle injury markers including CK, LDH, IL-6, TNF-α, and ferroptosis-related indicators such as Fe2+, MDA, COX2, and GPX4. Transmission electron microscopy was used to observe the morphology of mitochondria. JC-1, DHE, and C11-BODIPY 581/591 probes were used to detect mitochondrial membrane potential, mitochondrial reactive oxygen species (mtROS), and lipid peroxidation levels.
RESULTS: The results of this study indicate that GA has a positive therapeutic effect on skeletal muscle inflammation and injury induced by excessive exercise. On the one hand, GA can alleviate skeletal muscle mitochondrial injury and redox imbalance by reducing mitochondrial membrane potential level and increasing ATP production. On the other hand, GA can inhibit ferroptosis in skeletal muscle cells induced by excessive exercise through its antioxidant and anti-iron accumulation ability.
CONCLUSIONS: In summary, GA protects against skeletal muscle injury induced by excessive exercise by inhibiting mitochondrial oxidative stress and ferroptosis pathways, providing new evidence for GA as a promising therapeutic agent for skeletal muscle injury.

Keywords:  Excessive exercise; Ferroptosis; Gallic acid; Mitochondrial oxidative stress; Skeletal muscle injury

DOI:  https://doi.org/10.1186/s12967-024-06042-5
Nutrients. 2024 Dec 23. pii: 4419. [Epub ahead of print]16(24):

Curcumin Modulates Platelet Activation and ROS Production Induced by Amyloid Peptides: New Perspectives in Attenuating Prothrombotic Risk in Alzheimer's Disease Patients.

Serena Rustichelli, Cristina Lanni, Marta Zarà, Gianni Francesco Guidetti, Mauro Torti, Ilaria Canobbio.

   BACKGROUND/OBJECTIVES: Amyloid peptides, whose accumulation in the brain as senile plaques is associated with the onset of Alzheimer's disease, are also found in cerebral vessels and in circulation. In the bloodstream, amyloid peptides promote platelet adhesion, activation, oxidative stress, and thrombosis, contributing to the cardiovascular complications observed in Alzheimer's disease patients. Natural compounds, such as curcumin, are known to modulate platelet activation induced by the hemostatic stimuli thrombin and convulxin. In this study, we investigated the ability of curcumin to modulate platelet activation triggered by amyloid peptides, and we compared its effects with those displayed on platelet activation induced by physiological agonists.
METHODS: Commercial ultrapure curcumin was used, and platelet aggregation, granule secretion, phosphorylation of selected signaling proteins, and reactive oxygen species production were analyzed on isolated human platelets.
RESULTS: Our results demonstrate that curcumin effectively suppressed platelet aggregation induced by fibrillar amyloid peptides. This effect was associated with the reduction in intracellular signaling pathways involving PKC, PI3K, and MAPK. By contrast, platelet aggregation and activation induced by thrombin and convulxin were only partially reduced by preincubation with curcumin. Moreover, curcumin completely suppressed granule secretion only when platelets were stimulated with hemostatic agonists, but it had no effects upon stimulation with amyloid peptides. Additionally, curcumin reduced the production of reactive oxygen species induced by amyloid peptides with a stronger efficiency compared to platelets stimulated with thrombin.
CONCLUSIONS: These results indicate that curcumin displays selective and potent inhibitory activity on platelet responses to pathological stimuli, such as fibrillar amyloid peptides.

Keywords:  amyloid peptides; curcumin; platelet activation; reactive oxygen species

DOI:  https://doi.org/10.3390/nu16244419
Antioxidants (Basel). 2024 Nov 28. pii: 1462. [Epub ahead of print]13(12):

Role of Oxidative Stress in Blood-Brain Barrier Disruption and Neurodegenerative Diseases.

Sehwan Kim, Un Ju Jung, Sang Ryong Kim.

  Upregulation of reactive oxygen species (ROS) levels is a principal feature observed in the brains of neurodegenerative diseases such as Parkinson's disease (PD) and Alzheimer's disease (AD). In these diseases, oxidative stress can disrupt the blood-brain barrier (BBB). This disruption allows neurotoxic plasma components, blood cells, and pathogens to enter the brain, leading to increased ROS production, mitochondrial dysfunction, and inflammation. Collectively, these factors result in protein modification, lipid peroxidation, DNA damage, and, ultimately, neural cell damage. In this review article, we present the mechanisms by which oxidative damage leads to BBB breakdown in brain diseases. Additionally, we summarize potential therapeutic approaches aimed at reducing oxidative damage that contributes to BBB disruption in neurodegenerative diseases.

Keywords:  blood-derived protein; blood–brain barrier; neurodegenerative diseases; oxidative damage; reactive oxygen species

DOI:  https://doi.org/10.3390/antiox13121462
Naunyn Schmiedebergs Arch Pharmacol. 2025 Jan 09.

Senkyunolide I prevent chondrocytes from oxidative stress through Nrf2/HO-1 signaling pathway.

Pengbin Li, Wenjuan Tang, Haiyan Wen, Siqi Zhou, Hui Cao.

  Osteoarthritis (OA) is a degenerative musculoskeletal disease, featured by the destruction of articular cartilage. Oxidative stress, one of the drivers of the extracellular matrix degradation in cartilage, plays a vital role in OA pathogenesis. Senkyunolide I (SEI) is a natural compound with a prominent anti-oxidative stress property against multiple diseases. However, the protective effect of SEI on OA has not been explored. Here, we aimed to elucidate the effect of SEI on OA in vitro. Our results showed that SEI suppressed the expression of senescence-related markers such as P16 and P21 in IL-1β-induced chondrocytes. Besides, SEI alleviated IL-1β-induced the degradation of extracellular matrix (ECM) by suppressing the matrix proteinase like MMP13 and ATAMDS5 while promoting matrix synthesis regulated biomarkers like COL2A1 and ACAN in chondrocytes. Mechanically, the mitochondrial dysfunction and overproduction of intracellular reactive oxygen species (ROS) in chondrocytes induced by IL-1β were reversed by SEI. Additionally, the ROS inhibitor N-acetylcysteine (NAC) synergistically enhanced the biological effect of SEI in IL-1β-induced chondrocytes. Moreover, it was also found that the expression of Nrf2 and HO-1 was increased by the treatment of SEI in IL-1β-stimulated chondrocytes, while the Nrf2 inhibitor ML385 reversed the protective effect of SEI on OA chondrocytes. In conclusion, SEI could inhibit senescence, the degradation of ECM, and the production of ROS through activating Nrf2/ HO-1 signaling pathway, which provide a novel candidate for OA treatment.

Keywords:  Nrf2/HO-1 signaling pathway; Osteoarthritis; Oxidative stress; Senescence; Senkyunolide I

DOI:  https://doi.org/10.1007/s00210-024-03776-3
Int J Mol Sci. 2024 Dec 13. pii: 13400. [Epub ahead of print]25(24):

The Roles of Oxidative Stress and Red Blood Cells in the Pathology of the Varicose Vein.

Lukasz Gwozdzinski, Anna Pieniazek, Krzysztof Gwozdzinski.

  This review discusses sources of reactive oxygen species, enzymatic antioxidant systems, and low molecular weight antioxidants. We present the pathology of varicose veins (VVs), including factors such as hypoxia, inflammation, dysfunctional endothelial cells, risk factors in varicose veins, the role of RBCs in venous thrombus formation, the influence of reactive oxygen species (ROS) and RBCs on VV pathology, and the role of hemoglobin in the damage of particles and macromolecules in VVs. This review discusses the production of ROS, enzymatic and nonenzymatic antioxidants, the pathogenesis of varicose veins as a pathology based on hypoxia, inflammation, and oxidative stress, as well as the participation of red blood cells in the pathology of varicose veins.

Keywords:  oxidative stress; reactive oxygen species; red blood cell; varicose vein

DOI:  https://doi.org/10.3390/ijms252413400
Int J Mol Sci. 2024 Dec 18. pii: 13576. [Epub ahead of print]25(24):

Understanding the Molecular Impact of Physical Exercise on Alzheimer's Disease.

Alba Cantón-Suárez, Leticia Sánchez-Valdeón, Laura Bello-Corral, María J Cuevas, Brisamar Estébanez.

  Alzheimer's disease is one of the most common neurodegenerative diseases, characterized by a wide range of neurological symptoms that begin with personality changes and psychiatric symptoms, progress to mild cognitive impairment, and eventually lead to dementia. Physical exercise is part of the non-pharmacological treatments used in Alzheimer's disease, as it has been shown to delay the neurodegenerative process by improving the redox state in brain tissue, providing anti-inflammatory effects or stimulating the release of the brain-derived neurotrophic factor that enhances the brain structure and cognitive performance. Here, we reviewed the results obtained from studies conducted in both animal models and human subjects to comprehend how physical exercise interventions can exert changes in the molecular mechanisms underlying the pathophysiological processes in Alzheimer's disease: amyloid β-peptide pathology, tau pathology, neuroglial changes, mitochondrial dysfunction, and oxidative stress. Physical exercise seems to have a protective effect against Alzheimer's disease, since it has been shown to induce positive changes in some of the biomarkers related to the pathophysiological processes of the disease. However, additional studies in humans are necessary to address the current lack of conclusive evidence.

Keywords:  Alzheimer’s disease; amyloid β-peptide; mitochondrial dysfunction; molecular mechanisms; neurodegeneration; neuroglia; oxidative stress; physical activity; tau protein

DOI:  https://doi.org/10.3390/ijms252413576
Curr Drug Targets. 2025 Jan 06.

Repurposing Nano Curcumin: Unveiling its Therapeutic Potential in Diabetic Nephropathy.

Rarchita Sharma, Yogesh Mali, Yogeeta O Agrawal, Vinit V Agnihotri, Sameer N Goyal.

  Currently, diabetic nephropathy (DN) stands as the predominant global cause of endstage renal disease. Many scientists believe that diabetes will eventually spread to pandemic levels due to the rising prevalence of the disease. While the primary factor leading to diabetic nephropathy is vascular dysfunction induced by hyperglycemia, several other pathological elements, such as fibrosis, inflammation, and oxidative stress, also contribute to the progression of the disease. The primary targets of current DN therapy approaches are the underlying abnormalities of hypertension and glucose. With several targets and fewer side effects, curcumin is a commonly utilized antioxidant in DN. The present study emphasizes the critical role of oxidative stress and inflammation in the development of diabetic nephropathy. It reveals how these factors induce damage in key kidney cell types, highlighting their potential as therapeutic targets for this disease. In addition, by concentrating on Nrf2, SIRT1, HMGB1, NF-κB, and NLRP3 of curcumin, has strong anti- inflammatory and antioxidant characteristics. This review describes the role of curcumin in the therapeutic application of diabetic nephropathy. In this attempt, we tried to elaborate on the bench-to-bedside aspects of curcumin in DN, including clinical and preclinical investigations. The rationales of curcumin's mechanisms in alleviating symptoms of the DN were discussed. Curcumin could serve as the potential therapeutic agent for the patient seeking to recover from DN.

Keywords:  Diabetic nephropathy; autophagy; clinical trials; curcumin; oxidative stress.

DOI:  https://doi.org/10.2174/0113894501326054241126043554
Invest Ophthalmol Vis Sci. 2025 Jan 02. 66(1): 17

Idebenone Protects Photoreceptors Impaired by Oxidative Phosphorylation Disorder in Retinal Detachment.

Lisong Wang, Gaocheng Zou, Yuanye Yan, Ronghua Shi, Yue Guo, Mei Zhang, Li Lu, Kai Dong.

Purpose: Oxidative phosphorylation (OXPHOS) is an aerobic metabolic mechanism, and its dysfunction plays an important role in the pathological changes of ischemic diseases. However, systematic studies on the occurrence of retinal detachment (RD) are lacking.
Methods: Single-cell RNA sequencing (scRNA-seq) of the human retina was performed to detect the metabolic changes of various retinal cells after RD. In this study, animal experiments were conducted to explore the OXPHOS activity after RD. In addition, idebenone, a coenzyme Q10 (CoQ10) analog currently used to treat Leber hereditary optic neuropathy (LHON), was used to improve the OXPHOS disorder in experimental RD model.
Results: ScRNA-seq revealed abnormal energy metabolism and OXPHOS pathways in retinal cells after RD. Adenosine triphosphate (ATP) and reactive oxygen species (ROS) are the main products of OXPHOS, the mouse RD model indicated that the rise in ROS levels may have a greater impact on photoreceptors in the early stage, whereas decreased ATP synthesis was observed in the later stage; these changes threaten the function and morphology of the retina. Idebenone was administered to model mice intragastrically, leading to reduced ROS levels in the early stage post-RD and improved ATP synthesis in the later stage, which was closely related to the maintenance of mitochondrial morphology.
Conclusions: OXPHOS disorder leads to photoreceptor degeneration after RD, which can be alleviated by improving OXPHOS function.

DOI: https://doi.org/10.1167/iovs.66.1.17
Amino Acids. 2025 Jan 10. 57(1): 6

Taurine prevents mitochondrial dysfunction and protects mitochondria from reactive oxygen species and deuterium toxicity.

Stephanie Seneff, Anthony M Kyriakopoulos.

  Taurine, although not a coding amino acid, is the most common free amino acid in the body. Taurine has multiple and complex functions in protecting mitochondria against oxidative-nitrosative stress. In this comprehensive review paper, we introduce a novel potential role for taurine in protecting from deuterium (heavy hydrogen) toxicity. This can be of crucial impact to either normal or cancer cells that have highly different mitochondrial redox status. Deuterium is an isotope of hydrogen with a neutron as well as a proton, making it about twice as heavy as hydrogen. We first explain the important role that the gut microbiome and the gut sulfomucin barrier play in deuterium management. We describe the synergistic effects of taurine in the gut to protect against the deleterious accumulation of deuterium in the mitochondria, which disrupts ATP synthesis by ATPase pumps. Moreover, taurine's derivatives, N-chlorotaurine (NCT) and N-bromotaurine (NBrT), produced through spontaneous reaction of taurine with hypochlorite and hypobromite, have fascinating regulatory roles to protect from oxidative stress and beyond. We describe how taurine could potentially alleviate deuterium stress, primarily through metabolic collaboration among various gut microflora to produce deuterium depleted nutrients and deuterium depleted water, and in this way protect against leaky gut barrier, inflammatory bowel disease, and colon cancer.

Keywords:  Cancer; Deuterium; Mitochondrial dysfunction; Short chain fatty acids, Gut microbiome; Taurine

DOI:  https://doi.org/10.1007/s00726-024-03440-3
CNS Neurol Disord Drug Targets. 2025 Jan 08.

Anti-neuroinflammatory and Neuroprotective Effects of T-006 on Alzheimer's Disease Models by Modulating TLR4-Mediated MyD88/ NF-κB Signaling.

Haiyun Chen, Xiao Chang, Jiemei Zhou, Guiliang Zhang, Jiehong Cheng, Zaijun Zhang, Jieyu Xing, Chunyan Yan, Zheng Liu.

   INTRODUCTION: Neuroinflammation derived from the activation of the microglia is considered a vital pathogenic factor of Alzheimer's Disease (AD). T-006, a tetramethylpyrazine derivative, has been found to alleviate cognitive deficits via inhibiting tau expression and phosphorylation in AD transgenic mouse models. Recently, T-006 has been proven to dramatically decrease the levels of total Amyloid β (Aβ) peptide and Glial Fibrillary Acidic Protein (GFAP) and suppress the expression of ionized calcium binding adaptor molecule-1 (Iba-1) in APP/PS1 mice. Therefore, we have further investigated the effects of T-006 on neuroinflammation in AD-like pathology.
METHODS: The anti-inflammatory effects of T-006 and its underlying mechanisms were evaluated in Lipopolysaccharide (LPS)-induced AD rats. The potential protective effects against LPS-activated microglia-mediated neurotoxicity were also measured.
RESULTS: T-006 significantly improved the cognitive impairment in LPS-induced AD rats by inhibiting the microglia/astrocyte activation. Further cellular assays found that T-006 significantly reserved the anomalous elevation of inflammatory cytokines in LPS-induced BV2 microglial cells in a concentration-dependent manner, while T-006 treatment alone showed no effects on the normal cultured cells. T-006 also reduced the levels of Toll-like Receptor 4 (TLR4)/Myeloid Differentiation protein-88 (MyD88)/NF-κB signaling-related proteins in BV2 cells exposed to LPS stimulation. TAK242, which selectively inhibits TLR4, slightly lessened the effects of T-006 in LPS-treatment BV2 cells without significance. Importantly, T-006 protected neurons against LPS-induced neuroinflammation by inhibiting the Reactive Oxygen Species (ROS) production and maintaining mitochondrial function.
CONCLUSION: T-006 inhibited TLR4-mediated MyD88/NF-κB signaling pathways to suppress neuroinflammation in the LPS-induced AD rat model.

Keywords:  Alzheimer's disease.; MyD88/NF-κB signaling pathways; T-006; TLR4; Tetramethylpyrazine derivative; microglial activation; neuroinflammation

DOI:  https://doi.org/10.2174/0118715273337232241121113048
Nutrients. 2024 Dec 18. pii: 4368. [Epub ahead of print]16(24):

Mechanisms and Potential Benefits of Neuroprotective Agents in Neurological Health.

Burcu Pekdemir, António Raposo, Ariana Saraiva, Maria João Lima, Zayed D Alsharari, Mona N BinMowyna, Sercan Karav.

  The brain contains many interconnected and complex cellular and molecular mechanisms. Injury to the brain causes permanent dysfunctions in these mechanisms. So, it continues to be an area where surgical intervention cannot be performed except for the removal of tumors and the repair of some aneurysms. Some agents that can cross the blood-brain barrier and reach neurons show neuroprotective effects in the brain due to their anti-apoptotic, anti-inflammatory and antioxidant properties. In particular, some agents act by reducing or modulating the accumulation of protein aggregates in neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, Huntington's disease, Amyotrophic lateral sclerosis, and prion disease) caused by protein accumulation. Substrate accumulation causes increased oxidative stress and stimulates the brain's immune cells, microglia, and astrocytes, to secrete proinflammatory cytokines. Long-term or chronic neuroinflammatory response triggers apoptosis. Brain damage is observed with neuronal apoptosis and brain functions are impaired. This situation negatively affects processes such as motor movements, memory, perception, and learning. Neuroprotective agents prevent apoptosis by modulating molecules that play a role in apoptosis. In addition, they can improve impaired brain functions by supporting neuroplasticity and neurogenesis. Due to the important roles that these agents play in central nervous system damage or neurodegenerative diseases, it is important to elucidate many mechanisms. This review provides an overview of the mechanisms of flavonoids, which constitute a large part of the agents with neuroprotective effects, as well as vitamins, neurotransmitters, hormones, amino acids, and their derivatives. It is thought that understanding these mechanisms will enable the development of new therapeutic agents and different treatment strategies.

Keywords:  anti-inflammatory; antioxidant; neurodegenerative; neuroplasticity; neuroprotection

DOI:  https://doi.org/10.3390/nu16244368
Medicina (Kaunas). 2024 Dec 23. pii: 2110. [Epub ahead of print]60(12):

Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells.

Ali Aslan, Mücahit Seçme.

  Background and Objectives: Neuroblastoma is the most common extracranial solid tumor in children, often presenting challenges in treatment due to its clinical and genetic heterogeneity. This study investigated the anticancer potential of Pelargonium sidoides root extract on the human neuroblastoma cell line (SH-SY5Y). Using XTT assays, ELISA-based oxidative stress markers, and RT-PCR analysis of apoptotic genes, the study explored the extract's effects on cell proliferation, oxidative stress, and apoptosis. Materials and Methods: For the cell culture, SH-SY5Y human neuroblastoma cells were thawed, cultured, and maintained under appropriate conditions for experiments. The dose- and time-dependent activity of Pelorgonium sidoides extract on SH-SY5Y neuroblastoma cells was investigated by XTT assay. The change in the oxidative stress marker 8-Hydroxy-2'-deoxyguanosine (8-OhDG) level was determined by ELISA for the doses applied to the control group root extract at a concentration of 25 μg/mL. Total antioxidant status (TAS) and total oxidant status (TOS) were measured from the cells in the study group with the help of a commercial kit. The oxidative stress index (OSI) was calculated by dividing the TAS by the TOS and multiplying by 100. In order to evaluate the expression levels of apoptosis-related Bax, Bcl-2, Caspase-3, Caspase-8, and Caspase-9 genes at the mRNA level in control and dose group cells, RNA isolation was performed from the SH-SY5Y control and dose group cells (IC50 value). Results: It is observed that the P. sidoides substance inhibits proliferation in cells at 24 h (p < 0.05). As the dose increases, cell proliferation decreases (p < 0.05). The IC50 value was calculated to be 113.83 μg/mL at 24 h. The concentration of 8-OhDG increased in neuroblastoma cells as a result of P. sidoides extract treatment (p < 0.05). TOS levels increased in neuroblastoma cells treated with P. sidoides extract (p < 0.01). OSI levels increased in cells treated with P. sidoides extract (p < 0.001). BAX and Caspase-8 expression increased are statistically significant in the P. sidoides dose group (p < 0.05). Conclusions: P. sidoides extract induces apoptosis in neuroblastoma cells through oxidative stress and mitochondrial- and death receptor-mediated pathways. This study highlights the potential of P. sidoides as a complementary therapeutic agent for neuroblastoma, warranting further in vivo and clinical investigations to assess its safety and efficacy.

Keywords:  P. sidoides; SH-SY5Y; apoptosis; cell line; neuroblastoma; oxidative stress

DOI:  https://doi.org/10.3390/medicina60122110
Sci Rep. 2025 Jan 09. 15(1): 1542

Pterostilbene protects against lipopolysaccharide-induced inflammation and blood-brain barrier disruption in immortalized brain endothelial cell lines in vitro.

Yan Zhou, Yifan Yang, Rui Tian, Wai San Cheang.

  Brain microvascular endothelial cells are connected by tight junction (TJ) proteins and interacted by adhesion molecules, which participate in the selective permeability of the blood-brain barrier (BBB). The disruption of BBB is associated with the progression of cerebral diseases. Pterostilbene is a natural compound found in blueberries and grapes with a wide range of biological activities, including anti-inflammatory, antioxidant, and anti-diabetic effects. In this study, we investigated the protective effects of pterostilbene on LPS-stimulated mouse brain endothelial (bEnd.3) cells and underlying mechanisms. The results showed that pterostilbene effectively upregulated the expressions of tight junction (TJ) proteins such as zonula occludens (ZO)-1 and claudin-5 and downregulated the expression of adhesion molecules such as intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1, preventing BBB damage under LPS stimulation. Pterostilbene decreased the LPS-triggered expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 as well as the levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α and nitric oxide (NO). Meanwhile, we found that pterostilbene exerted an inhibitory effect on nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways in bEnd.3 cells upon LPS stimulation. Additionally, pterostilbene exhibited antioxidant effects by activating heme oxygenase 1 (HO-1). These findings indicated that pterostilbene protected against lipopolysaccharide (LPS)-induced inflammation, oxidative stress and blood-brain barrier (BBB) disruption in bEnd.3 cells.

Keywords:  Adhesion molecules; Blood–brain barrier; Brain endothelial cells; Inflammation; Lipopolysaccharide; Oxidative stress; Pterostilbene; Tight junction proteins

DOI:  https://doi.org/10.1038/s41598-025-85144-6
Arch Virol. 2025 Jan 06. 170(2): 27

Undaria pinnatifida fucoidan extract inhibits activation of the NF-κB signaling pathway by herpes simplex virus type 1 and prevents amyloid-β peptide synthesis in retinal pigment epithelium cells.

Macarena Giuliani, Camila Uboldi, Fernando Gaspar Dellatorre, Ezequiel Latour, Nora Marta Andrea Ponce, Carlos A Stortz, Verónica Leticia Lassalle, Victoria Belen Ayala-Peña.

Neurodegenerative pathologies such as age-related macular degeneration currently have no cure or effective treatment. In this type of disease, the presence of amyloid-β peptides, oxidative stress, and inflammation trigger dysregulation of retinal pigment epithelial cells and progression toward the death of these cells, resulting in a loss of vision. The production of amyloid-β peptides, oxidative stress, and inflammation can be triggered in response to viral infections. Fucoidans are sulfated polysaccharides that are present in the cell walls of brown algae. There is a large body of literature reporting a wide range of biological properties of these compounds. In this study, we investigated whether Undaria pinnatifida fucoidan extract can prevent infection with herpes simplex virus type 1 and if the extract has antioxidant activity. We also evaluated whether, under viral infection conditions, the synthesis of amyloid-β peptide and NF-κB activation could be inhibited by the extract. The results showed for the first time that this extract can prevent viral infection in retinal pigment epithelial cells and that they can prevent the formation of amyloid-β peptide and the activation of the NF-κB pathway during viral infection. We also found that Undaria pinnatifida fucoidan extract has antioxidant activity and reduces the levels of reactive oxygen species. These data suggest that Undaria pinnatifida fucoidan extract might be effective for treating diseases triggered by viral infections, such as degenerative retinal diseases.

DOI: https://doi.org/10.1007/s00705-024-06212-2
Eur J Nutr. 2025 Jan 07. 64(1): 64

Ellagic acid alleviates DSS-induced ulcerative colitis by inhibiting ROS/NLRP3 pathway activation and modulating gut microbiota in mice.

Yanling Xiong, Zhentao Cheng, Yangzi Zhang, Ting Liu, Zhiling Wan, Cuiyun Xia, Binlan Zhou, Chunlan Shan, Derong Song, Fujun Miao.

  Ulcerative colitis (UC) can cause severe oxidative stress in the colon, which can lead to tissue damage and an imbalance in the normal gut microbiota. Ellagic acid (EA) is one of the main types of plant polyphenols with improved pharmacological effects such as antioxidant, anti-inflammatory, and antibacterial properties. However, currently, the studies on the impact of EA on the gut microbiota and its potential to alleviate UC in mice through the ROS/NLRP3 pathway are limited. In this study, dextran sodium sulfate (DSS) was used to construct a UC mouse model, which was then treated with EA as an intervention for UC. The results revealed that EA alleviated the trend of liver, spleen, and weight changes in UC mice and improved colon oxidative stress, inflammation, and pathological damage. Mechanistically, DSS-induced UC indicated a significant increase in ROS/NLRP3 pathway-related factors, whereas EA intervention activated the Nrf2 pathway to reduce these factors. Furthermore, the DSS group had a reduced abundance of Firmicutes (59.02%) and an increased abundance of Bacteroides and Proteobacterium by 1.8 times and 10.16%; however, EA intervention reversed these changes, thus alleviating UC. The findings of this study revealed that EA could significantly enhance the composition of gut microbiota in UC and reduce the inflammatory response, colonic damage as well as oxidative stress caused by DSS by regulating the ROS/NLRP3 pathway. These results provide novel perspectives on the prevention and treatment strategies of UC and highlight the therapeutic benefits of EA in managing colitis.

Keywords:  Ellagic acid; Gut microbiota; Oxidative stress; ROS/NLRP3 pathway; Ulcerative colitis

DOI:  https://doi.org/10.1007/s00394-024-03577-7
ACS Chem Neurosci. 2025 Jan 10.

From Plant to Pathway: Molecular Mechanisms of Ruscogenin in Preventing Amyloid-Beta Aggregation through Computational and Experimental Approaches.

Aastha Tiwari, Ravinder Singh, Shubham Kumar, Aditya Sunkaria, Alok Jain.

  Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, extracellular amyloid-β (Aβ) plaque accumulation, and intracellular neurofibrillary tangles. Recent efforts to find effective therapies have increased interest in natural compounds with multifaceted effects on AD pathology. This study explores natural compounds for their potential to mitigate AD pathology using molecular docking, ADME screening, and in vitro assays, with ruscogenin─a steroidal sapogenin from Ruscus aculeatus─emerging as a promising candidate. Ruscogenin, known for its antioxidant and anti-inflammatory properties, was investigated for its effects on Aβ aggregation, a critical process in AD progression. In vitro assays demonstrated that ruscogenin inhibits Aβ oligomerization at equimolar and higher molar ratios. Molecular dynamics (MD) simulations further revealed that ruscogenin targets aggregation-prone regions, reducing noncovalent interactions and the solvent-accessible surface area of Aβ aggregates. These effects were concentration-dependent, with higher concentrations yielding optimal inhibition, pointing to a multiphasic behavior in ruscogenin's modulation of Aβ aggregation. This study highlights ruscogenin's potential as a natural therapeutic agent for AD, capable of addressing both oxidative stress and inflammation. The findings lay the groundwork for further exploration of ruscogenin-based interventions and underscore the broader potential of natural compounds in AD treatment strategies.

Keywords:  Alzheimer’s; amyloid-β inhibitors; in vitro; molecular dynamics and simulations; ruscogenin

DOI:  https://doi.org/10.1021/acschemneuro.4c00745
Antioxidants (Basel). 2024 Nov 23. pii: 1444. [Epub ahead of print]13(12):

MnSOD Mimetics in Therapy: Exploring Their Role in Combating Oxidative Stress-Related Diseases.

Jovan Grujicic, Antiño R Allen.

  Reactive oxygen species (ROS) are double-edged swords in biological systems-they are essential for normal cellular functions but can cause damage when accumulated due to oxidative stress. Manganese superoxide dismutase (MnSOD), located in the mitochondrial matrix, is a key enzyme that neutralizes superoxide radicals (O2•-), maintaining cellular redox balance and integrity. This review examines the development and therapeutic potential of MnSOD mimetics-synthetic compounds designed to replicate MnSOD's antioxidant activity. We focus on five main types: Mn porphyrins, Mn salens, MitoQ10, nitroxides, and mangafodipir. These mimetics have shown promise in treating a range of oxidative stress-related conditions, including cardiovascular diseases, neurodegenerative disorders, cancer, and metabolic syndromes. By emulating natural antioxidant defenses, MnSOD mimetics offer innovative strategies to combat diseases linked to mitochondrial dysfunction and ROS accumulation. Future research should aim to optimize these compounds for better stability, bioavailability, and safety, paving the way for their translation into effective clinical therapies.

Keywords:  MitoQ10; Mn porphyrins; Mn salens; MnSOD mimetics; mangafodipir; manganese superoxide dismutase (MnSOD); mitochondria-targeted antioxidants; nitroxides; oxidative stress; reactive oxygen species (ROS)

DOI:  https://doi.org/10.3390/antiox13121444
Acta Neurol Belg. 2025 Jan 07.

Brain insulin resistance mediated cognitive impairment and neurodegeneration: Type-3 diabetes or Alzheimer's Disease.

Abhilasha Ahlawat, Vaibhav Walia, Munish Garg.

  Insulin resistance is a condition characterized by the attenuated biological response in the presence of normal or elevated insulin level and therefore is characterized by the impaired sensitivity to insulin and impaired glucose disposal and utilization. Insulin resistance in brain/Brain insulin resistance (BIR) is accompanied by the various manifestations including alteration in glucose sensing by hypothalamic neurons, impaired sympathetic outflow in response to hypoglycemia, increased ROS production, impaired mitochondrial oxygen consumption in the brain, cognitive deficits and neuronal cell damage. It has been reported that the disrupted insulin signaling is accompanied by the reduced expression of insulin receptor (IR)/insulin receptor substrate 1 (IRS1)/PI3K/AKT and IGF-1 receptor (IGF-1R)/IRS2/PI3K pathways. Insulin resistance and impaired insulin signaling interferes with the degradation and transportation of Aβ leading to Aβ deposition. Aβ promotes the hyperphosphorylation of tau, accumulation of neurofibrillary tangles and the later promotes the neuro-inflammation, apoptosis, oxidative stress, impairments of energy metabolism, synaptic disconnections, and hippocampus atrophy. Therefore, the impaired insulin signaling and the insulin promote cognitive deficits and neuronal cell death in the affected individuals. BIR is mainly responsible for the cognitive deficits and the neuronal damage in the patients of Alzheimer's disease (AD). In the present work, authors describe the BIR, and its role in the emergence of cognitive deficits and neurodegeneration. Further, the emphasis has been given on the pharmacological agents that may alleviate the BIR and its deleterious effects.

Keywords:  Amyloid Beta; Cognitive impairment; Inflammatory responses neuronal death; Insulin resistance; Tau protein etc

DOI:  https://doi.org/10.1007/s13760-024-02706-7
Medicina (Kaunas). 2024 Nov 26. pii: 1949. [Epub ahead of print]60(12):

Oxidative/Nitrosative Stress and Brain Involvement in Sepsis: A Relationship Supported by Immunohistochemistry.

Giuseppe Bertozzi, Michela Ferrara, Mariagrazia Calvano, Natascha Pascale, Aldo Di Fazio.

  Background and Objectives: A large amount of recent evidence suggests that cellular inability to consume oxygen could play a notable part in promoting sepsis as a consequence of mitochondrial dysfunction and oxidative stress. The latter could, in fact, represent a fundamental stage in the evolution of the "natural history" of sepsis. Following a study previously conducted by the same working group on heart samples, the present research project aims to evaluate, through an immunohistochemical study, the existence and/or extent of oxidative stress in the brains of subjects who died due to sepsis and define, after reviewing the literature, its contribution to the septic process to support the use of medications aimed at correcting redox anomalies in the management of septic patients. Materials and Methods: 10 cases of subjects who died in healthcare facilities with ante-mortem clinical-laboratory signs that allowed the diagnosis of septic shock were selected as case studies, and 1 case of a subject who died immediately following a road traffic accident was used as a negative control. Samples of the cerebral cortex were then taken, fixed in formalin, and subjected to sections on which an immunohistochemical study was performed using anti-NOX-2, NT, iNOS, and 8-OHdG antibodies. Results: The results emerging from the present study demonstrate that despite a variable expressivity for the NT, iNOS, and NOX2 markers, the brain samples demonstrated univocal and high positivity for the 8-OHdG marker. Conclusions: This would allow us to hypothesize how, regardless of the mechanism of production of ROS and NOS (iNOS or NOX2 mediated) and the pathophysiological mechanisms that are triggered during sepsis, oxidative damage to DNA represents the event to which this whole process leads and, in fact, in the literature, is directly correlated to sepsis-dependent mortality. Neurons, conversely, appear to be more sensitive to oxidative stress because of a low number of protective or scavenger molecules (catalase, glutathione peroxidase, GSH, or vitamin E). Therefore, despite reduced production, the manifestation of the damage remains high. This evidence, together with that of the previous study, can only support the introduction of substances with an antioxidant function in the guidelines for the treatment of sepsis.

Keywords:  8-OHdG; NOX-2; NT; brain; iNOS; immunohistochemistry; nitrosative stress; sepsis

DOI:  https://doi.org/10.3390/medicina60121949
Int J Mol Sci. 2024 Dec 19. pii: 13624. [Epub ahead of print]25(24):

Quercetin Alleviates All-Trans-Retinal-Induced Photoreceptor Apoptosis and Retinal Degeneration by Inhibiting the ER Stress-Related PERK Signaling.

Bo Yang, Kunhuan Yang, Ruitong Xi, Jingmeng Chen, Yalin Wu.

  All-trans-retinal (atRAL)-induced photoreceptor atrophy and retinal degeneration are hallmark features of dry age-related macular degeneration (AMD) and Stargardt disease type 1 (STGD1). The toxicity of atRAL is closely related to the generation of reactive oxygen species (ROS). Quercetin, a natural product, is known for its potent antioxidant properties; however, its effects in mitigating atRAL-mediated retinal damage remains unclear. This study investigated the protective effects of quercetin against atRAL-induced photoreceptor damage. Using atRAL-loaded 661W photoreceptor cells, we evaluated cell viability, ROS generation, and endoplasmic reticulum (ER) stress under quercetin treatment. Quercetin significantly restored the cell viability (to 70%) and reduced ROS generation in atRAL-treated 661W cells. Additionally, Western blot analysis demonstrated that quercetin mitigated protein kinase RNA-like ER kinase (PERK) signaling, preventing ER stress-induced apoptosis. Importantly, in Abca4-/-Rdh8-/- mice, an animal model of light-induced atRAL accumulation in the retina, quercetin treatment effectively alleviated light-exposed photoreceptor atrophy and retinal degeneration by attenuating PERK signaling. Thus, quercetin protected photoreceptor cells from atRAL-induced damage by inhibiting ROS generation and PERK signaling, which suggests its potential as a therapeutic agent for atRAL-related retinal degeneration.

Keywords:  ER stress; all-trans-retinal; apoptosis; photoreceptor; quercetin

DOI:  https://doi.org/10.3390/ijms252413624
Phytother Res. 2025 Jan 10.

Berberine Inhibits the Disruption of the Blood-Brain Barrier and Glial Cell Activation in a Rat Model of Acute Hepatic Encephalopathy.

Syed Afroz Ali, Ashok Kumar Datusalia.

   BACKGROUND AND AIM: Hepatic encephalopathy (HE) is a complex neurological disorder in individuals with liver diseases, necessitating effective neuroprotective interventions to alleviate its adverse outcomes. Berberine (BBR), a natural compound with well-established anti-fibrotic and neuroprotective properties, has not been extensively studied in the context of glial activation under hyperammonaemic conditions. This study evaluates the neuroprotective potential of BBR in a thioacetamide (TAA)-induced HE rat model, focusing on its effects on glial activation and NLRP3 inflammasome signalling.
METHODS: Neurological impairments were assessed using open field tests and sensory analysis. Western blotting was performed to evaluate the expression of glial and neuronal markers, tight junction proteins and NLRP3 inflammasome components in the cortex and hippocampus. Histopathological and molecular changes were further examined using H&E, immunohistochemistry and immunofluorescence staining.
KEY RESULTS: BBR treatment significantly improved behavioural abnormalities and reduced systemic ammonia levels in TAA-exposed rats. It restored blood-brain barrier integrity, as evidenced by reduced tight junction protein degradation. BBR inhibited the expression of NLRP3 inflammasome markers, including caspase-1, IL-1β, ASC, and NF-κB, while reducing glial cell activation (IBA-1 and GFAP). Notably, BBR diminished NLRP3 expression in glial cells, indicating its potent anti-inflammatory effects. Additionally, BBR preserved neuronal integrity, as demonstrated by the maintained expression of MAP-2 and NeuN and reduced cleaved Gasdermin D levels.
CONCLUSIONS: These findings suggest that BBR alleviates behavioural and molecular abnormalities in HE through NLRP3 inflammasome inhibition, highlighting its potential as a therapeutic agent for managing HE.

Keywords:  NLRP3 inflammasome; astrocyte swelling; berberine; inflammatory signalling; microglial activation; neuroinflammation

DOI:  https://doi.org/10.1002/ptr.8430
Sci Rep. 2025 Jan 08. 15(1): 1293

Investigation of the anti-aging effects of active components of Artemia franciscana loaded in hyalurosome.

Mona Sadat Mirtaleb, Mahvash Khodabandeh Shahraky, Abdolkhaleg Deezagi, Danial Shafiee.

  With the advancement of biotechnology in the marine industry, an increasing utilization of marine ingredients in skincare products has been observed in recent years. Encapsulating Artemia franciscana extract and its derivatives in a novel phospholipid vesicle called hyalurosome presents innovative strategies for drug delivery systems and anti-aging products. In this study, we developed nano hyalurosomes containing Artemia franciscana active components. Partially purification of proteins in the Artemia franciscana extract was performed using ion exchange chromatography, specifically targeting Hsp40 and Artemin. The physicochemical properties of the hyalurosomes were characterized, revealing nanoparticle sizes ranging from 100 to 130 nm, zeta potential between - 57 and - 41.2 mV. The biological compatibility of the fabricated hyalurosomes was tested in vitro on mice fibroblast cells. Results indicated that formulations containing hyalurosomes exhibited no cytotoxicity. In-vivo studies employing H&E and Mason's trichrome staining demonstrated an increase in the dermal layer of the skin on male mice and collagen production following treatment with different formulations containing hyalurosomes. Therefore, these formulations are considered promising candidates for anti-aging effects. Stability study at 4 °C for 60 days validated by FE-SEM imaging. In conclusion, hyalurosomes fabricated with Artemia franciscana extract and its diverse active molecules successfully achieved enhanced loading and penetration into the deeper layers of the skin, and it can be a suitable candidate for the treatment of skin aging and rejuvenation.

Keywords:  Artemia franciscana; Hyalurosome; Marine biotechnology; Nano drug delivery; Skin regeneration

DOI:  https://doi.org/10.1038/s41598-024-83731-7