The presented study investigated possible antioxidant and anti-inflammatory properties of Vaccinium myrtillus (VM) extract in murine BV-2 microglial cells, including both wild-type (Wt) and Acyl-CoA oxidase 1-deficient (Acox1−/−) cell lines. The radical scavenging activity was assessed by DPPH assay. The MTT test was used assess the cell viability. Nitric oxide production by cells was quantified by Griess reagent. Catalase activity was evaluated by photometric measurement of the H2O2 decomposition. The measurement of ACOX1 activity was performed using a fluorometry-based assay. Immunoblotting and RT-qPCR techniques were employed to measure protein expression and gene transcription in treated cells. Statistical analysis was conducted using GraphPad Prism, with significance determined at p < 0.05. Radical scavenging activity test assessed the yielded an IC50 value 0.03613 mg/mL, prompting further functional investigations. Lipopolysaccharide (LPS) stimulation reduced ACOX1 enzymatic activity by approximately 40

Sepsis is characterized by an imbalance between excessive oxidative stress and endogenous antioxidant responses, leading to multi-organ dysfunction. The aim of this study was to investigate the protective effect of argan oil (AO) against lipopolysaccharide (LPS)-induced oxidative stress, with particular focus on peroxisomal-related antioxidant implications in liver, brain, kidney and heart. Phenolic and pigment contents (chlorophylls and carotenoids) of AO and olive oil (OO) were quantified, and antioxidant capacities determined in vitro using DPPH, ABTS, and FRAP assays. Mice were supplemented daily with AO or OO for 28 days prior to challenge with intraperitoneal injection of LPS (5 mg/kg) to induce acute oxidative stress. Although OO exhibited a higher phenolic content and more potent in vitro antioxidant activity across all assays, in vivo outcomes noted tissue-specific antioxidant efficacy. Antioxidant enzyme activities (superoxide dismutase, catalase, glutathione peroxidase) and glutathione levels as well as lipid peroxidation (malondialdehyde) were measured in the four target organs. LPS challenge initiated marked alterations in antioxidant defenses and increased oxidative damage in a tissue-dependent manner, with liver exhibiting the greatest response. AO supplementation efficiently mitigated LPS-induced redox imbalance, restoring antioxidant enzyme activities and limiting lipid peroxidation across organs, whereas OO displayed more variable and organ-dependent effects. These findings demonstrate that AO exerts significant in vivo antioxidant protection against LPS-induced oxidative stress despite lower in vitro antioxidant capacity than OO. Data show importance of tissue-specific and peroxisome-associated mechanisms in modulating oxidative stress responses and support AO as a promising nutritional strategy for attenuating sepsis-related organ dysfunction.

Oxidative stress plays a key role in tissue damage during inflammation, highlighting the need for effective antioxidant interventions. This study investigates the antioxidant potential of argan oil (AO)—obtained from Argania spinosa (L.) Skeels almonds—in comparison with olive oil (OO), cactus seed oil (CSO), and colza oil (CO). Quantitative analyses of total polyphenols and pigments—including chlorophylls, carotenoids, and xanthophylls—were conducted alongside antioxidant capacity assessments via DPPH, ABTS, and FRAP assays. The methanolic fraction consistently demonstrated the highest phenolic concentration and antioxidant efficacy across all oils. To establish in vivo relevance, a male C57BL/6J mouse model of acute oxidative stress was induced by lipopolysaccharide (LPS) administration. Pretreatment with oils significantly modulated key oxidative stress biomarkers—SOD, CAT, GPx activities, GSH levels, and lipid peroxidation (MDA)—in both heart and kidney. LPS challenge induced marked oxidative imbalance, notably increasing enzymatic activity and MDA levels, while depleting GSH in the heart and elevating it in the kidney. However, pretreatment with oils effectively restored redox homeostasis, with AO showing particularly potent effects and a stronger regulatory effect observed in the kidney. Hierarchical clustering of z-score-normalized heatmaps revealed distinct oxidative stress signatures, clearly separating LPS-treated heart and kidney tissues from other groups due to heightened oxidative markers. In contrast, oil-treated and oil-combined-with-LPS groups clustered closer to the control, underscoring the protective effect of oils against LPS-induced oxidative stress, with efficiency varying by oil type. Pearson correlation analysis, complemented by multivariate principal component analysis (PCA), further emphasized strong positive associations between antioxidant enzymes (SOD, CAT, GPx) and MDA levels, while GSH exhibited tissue-specific behavior—negatively correlated in the heart but positively in the kidney—highlighting divergent redox regulation between organs. Collectively, AO demonstrated robust cardioprotective and nephroprotective properties, supporting its potential as a natural dietary strategy against inflammation-induced oxidative stress.

Microglia, the immune cells of the central nervous system, activate neuroinflammatory pathways in response to homeostatic disturbances, a process implicated in the pathogenesis of various neurodegenerative diseases. Emerging evidence identifies abnormal microglial activation as a causal factor at the onset of peroxisomal leukodystrophies, including X-linked adrenoleukodystrophy (X-ALD). This study investigates how primary peroxisomal deficiencies influence oxidative properties of microglia and examines the subsequent impact on neurons and oligodendrocytes. Using BV-2 microglial cells lacking ABCD1, ABCD2, or ACOX1, peroxisomal proteins that play key roles in the very-long-chain fatty acid beta-oxidation, we analyzed their response under basal condition and after stimulation by lipopolysaccharide (LPS). Transcriptomic analysis of the mutant microglial cells revealed numerous differentially expressed genes, particularly in redox-related pathways following LPS exposure. These changes are consistent with the increased production of reactive oxygen species (ROS) and nitric oxide (NO). Conditioned media (CM) from the mutant cells were then applied to cultures of neuron and oligodendrocyte cell lines. Exposure to CM from LPS-stimulated mutant microglial cells significantly increased apoptosis in both cell types. Furthermore, treated neurons exhibited a reduction in cell complexity and an increased ability to secrete neuropeptides. These findings demonstrate that peroxisomal impairments in microglia exacerbate inflammatory response and ROS/NO production, affecting the survival of neurons and oligodendrocytes, as well as neuronal morphology and function. This dysfunction might contribute to the early neurodegenerative events in X-ALD by triggering and sustaining neuroinflammatory cascades. Therapeutic strategies that target microglial activation and secretion profiles could hold promise in managing peroxisomal disorders such as X-ALD.

This study focuses on the investigation of the antioxidant and anti-inflammatory activities of alcohol extracts from Ribes nigrum leaves on murine BV-2 microglial Wt and Acyl-CoA oxidase 1 deficient (Acox1−/−) cell line models, useful for the investigation of some neurodegenerative disorders. The extract chemical composition was analyzed via LC-Q-Orbitrap HRMS. Various assays, including DPPH, MTT, and H2DCFDA, were used to assess the extract’s antioxidant capacity, cell viability, and reactive oxygen species (ROS) production. Immunoblotting and RT-qPCR techniques were employed to measure protein expression and gene transcription in treated cells. Statistical analysis was conducted using GraphPad Prism, with significance determined at p < 0.05. Investigations showed the presence of phenolic compounds in this extract, among which flavan-3-ols, flavonols, furanocoumarins, hydroxycinnamates were major components, which are known for their biological activity in various test systems. The MTT test revealed a concentration of 0.125 mg/mL of R. nigrum extract as the highest non-toxic. The investigated extract showed high antioxidant activity in chemical-based tests. The antioxidant potential of the R. nigrum leaf extract was furtherly explored using the BV-2 microglial cell line models. Moreover, the extract was found to alter the activity of the main antioxidant enzyme, catalase and fatty acid oxidation enzyme, Acyl-CoA oxidase 1 (ACOX1) as well as the expression of appropriate genes in Wt and Acox1−/− BV-2 microglial cells such as Cat, iNos, Il-1β, Tnf-α, and Abcd1. In Wt cells, after the 24-hour treatment with R. nigrum leaf extract, ACOX1 activity was downregulated, meanwhile the catalase activity remains unchanged. Further treatment led to the downregulation of catalase and the upregulation of ACOX1 activity. However, in Acox1−/− cells, which represent a model of oxidative stress, an increase in catalase activity was observed only after 48 h of treatment. It was also observed the reduced ROS and NO formation in cells, showing the pronounced antioxidant capacity of R. nigrum extract in the investigated cell-models. Our study demonstrated the protective effects of R. nigrum leaf extracts on BV-2 microglial cells by reducing oxidative and nitrosative stress, decreasing pro-inflammatory gene expression, and normalizing peroxisomal function, highlighting the potential of these extracts as therapeutic agents for managing oxidative stress and inflammation.

Peroxisomes have gained increasing attention and are now considered vital players in normal physiological functions. To gain further insight into how peroxisomal defects influence cellular functions, we developed BV-2 microglial models featuring CRISPR/Cas9 gene-edited mutations in peroxisomal Acox1 or Abcd1 and Abcd2 genes. The Acox1−/− BV-2 cell line we generated lacks acyl-CoA oxidase 1, the key enzyme that initiates peroxisomal β-oxidation. In contrast, the double mutant Abcd1/d2−/− BV-2 cell line carries mutations in the genes encoding the membranous ABC transporters ABCD1 and ABCD2, which are responsible for transporting fatty acyl-thioesters inside peroxisome. Here, for the first time, we used analytical fractionation to compare these three genotypes. Through flow cytometry, we observed an increase in cell granularity in these mutant cells, which could be associated with alterations in peroxisome distribution and mitochondrial dynamics. Additionally, the analysis of organelle markers in microglial cells, employing differential centrifugation, exhibited an enrichment of peroxisomes particularly in both L and P fractions of these BV-2 cell line models. The use of an isopycnic Nycodenz density gradient showed that peroxisomes sedimented with a median density of 1.18 g/ml. Notably, our results revealed no significant differences in the distribution profiles of organelles when comparing microglial BV-2 Wt cells with deficient Acox1‒/‒ or Abcd1/d2−/‒ BV-2 cells, which lack peroxisomal fatty acid beta-oxidation. Our study is the first to report on the fractionation of brain-derived microglial cells, laying valuable groundwork for future proteomic and/or metabolomic analyses of peroxisome fractions.

Nutrition is a key determinant in modulating disease risk, with numerous studies highlighting the role of antioxidants and lipids, particularly the micronutrient and fatty acid composition of natural oils and their bioactive metabolites. In this context, argan oil—a vegetable oil extracted from the kernels of Argania spinosa—has gained significant attention due to its well-balanced fatty acid profile, rich in oleic and linoleic acids, and its high levels of antioxidant compounds, including tocopherols, polyphenols, and phytosterols, particularly schottenol and spinasterol. Thanks to its unique composition, argan oil exhibits protective properties against harmful biological processes, such as oxidative stress and inflammation, both of which play a significant role in various diseases. Preclinical studies, both in vitro and in vivo, have demonstrated that argan oil reduces oxidative stress by preventing DNA damage, protein carbonylation, and lipid peroxidation, while simultaneously increasing antioxidant defenses. Furthermore, it modulates inflammatory responses by decreasing pro-inflammatory biomarkers, increasing anti-inflammatory markers, and limiting immune cell infiltration across different tissues. These antioxidant and anti-inflammatory effects are thought to be linked to argan oil’s ability to regulate key signaling pathways, such as Nrf-2 and NF-κB. Although direct evidence remains limited, studies suggest that its main bioactive components—fatty acid, γ-tocopherol, ferulic acid, and campesterol—can influence these pathways, either by activating Nrf2 to boost antioxidant defenses or by inhibiting NF-κB to suppress inflammation. This review explores the antioxidant and anti-inflammatory properties of argan oil, drawing insights from a range of scientific studies to better understand its therapeutic potential.

Virgin Argan Oil (VAO) is extracted from the fruits of the Moroccan endemic species argan [Argania spinosa (L.) Skeels]. It is known for its richness in polyunsaturated fatty acids and its unique composition in tocopherols conferring a panoply of pharmacological properties, documented in several studies. The aim of this study was to investigate the potential protective effect of VAO against oxidative and nitrosative stress induced in cells of the model species Tetrahymena pyriformis. As a comparison, well-known Virgin Olive Oil (VOO) from Olea europaea L. was used instead. Both oils were subjected to a preliminary analysis of phytochemicals and properties of interest. Oxidative stress in T. pyriformis cells was induced by hydrogen peroxide (H2O2) at 350µM, whereas sodium nitroprusside (SNP) nitrosative stress was induced using a 1mM concentration. Neither of these concentrations caused relevant changes in cell viability. The level of reactive oxygen species (ROS) was evaluated in the cell cultures by using H2-DCFDA dye. The activity and cell localization of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPX) was evaluated as well as the levels of glutathione (GSH) and the malondialdehyde (MDA) generated after lipid peroxidation. Finally, the presence and localization of intracellular lipid droplets was assessed by using Nile red. The treatment of cultures with H2O2 produced significant increases in the activity of CAT, SOD and GPX and in the level of GSH, as also did the SNP treatment. MDA level was increased by both the treatments. VAO and VOO treatment were found to protect T. pyriformis from oxidative stress and increased cells defense in nitrosative stress. In another hand VAO and VOO decreased significantly MDA level increased by H2O2 treatment and failed after SNP treatment. The quantification of fluorescence signal obtained from immunolocalization of antioxidant enzymes confirmed the results obtained after the evaluation of their activities. Interestingly the level of ROS and the number of lipid droplets increased by H2O2 treatment was significantly decreased by VAO and VOO co-treatments. VAO and VOO represent strong antioxidants, playing an important role in protecting cells against oxidative stress.

Axis-driven random walks were introduced by P. Andreoletti and P. Debs [AD23] to provide a rough description of the behaviour of a particle trapped in a localized force field. In contrast to their work, we examine the scenario where a repulsive force (controlled by a parameter $\alpha$) is applied along the axes, with the hypothesis that the walk remains diffusive within the cones. This force gradually pushes the particle away from the origin whenever it encounters an axis. We prove that even with a minimal force (i.e., a small $\alpha$), the walk exhibits transient, superdiffusive behaviour, and we derive the left and right tails of its distribution.

Axis-driven random walks were introduced by P. Andreoletti and P. Debs [AD23] to provide a rough description of the behaviour of a particle trapped in a localized force field. In contrast to their work, we examine the scenario where a repulsive force (controlled by a parameter α) is applied along the axes, with the hypothesis that the walk remains diffusive within the cones. This force gradually pushes the particle away from the origin whenever it encounters an axis. We prove that even with a minimal force (i.e., a small α), the walk exhibits transient, superdiffusive behaviour, and we derive the left and right tails of its distribution.

In recent years, research on the discovery of natural compounds with potent antioxidant properties has resulted in growing interest in these compounds due to their potential therapeutic applications in oxidative-stress-related diseases. Argan oil, derived from the kernels of a native tree from Morocco, Argania spinosa, is renowned for its rich composition of bioactive compounds, prominently tocopherols, polyphenols, and fatty acids. Interestingly, a large body of data has shown that several components of argan oil activate the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, playing a crucial role in the cellular defense against oxidative stress. Activation of this Nrf2 pathway by argan oil components leads to the increased expression of downstream target proteins like NAD(P)H quinone oxidoreductase (NQO1), superoxide dismutase (SOD), heme oxygenase 1 (HO-1), and catalase (CAT). Such Nrf2 activation accounts for several health benefits related to antioxidant defense, anti-inflammatory effects, cardiovascular health, and neuroprotection in organisms. Furthermore, the synergistic action of the bioactive compounds in argan oil enhances the Nrf2 pathway. Accordingly, the modulation of the Kelch-like ECH associated protein 1 (Keap1)/Nrf2 signaling pathway by these components highlights the potential of argan oil in protecting cells from oxidative stress and underlines its relevance in dietetic prevention and therapeutic applications. This review aims to provide an overview of how major compounds in argan oil activate the Nrf2 pathway, updating our knowledge on their mechanisms of action and associated health benefits.

In this work, we are interested in the set of visited vertices of a tree $\mathbb{T}$ by a randomly biased random walk $\mathbb{X}:=(X_n,n \in \mathbb{N})$. The aim is to study a generalized range, that is to say the volume of the trace of $\mathbb{X}$ with both constraints on the trajectories of $\mathbb{X}$ and on the trajectories of the underlying branching random potential $\mathbb{V}:=(V(x), x \in \mathbb{T})$. Focusing on slow regime's random walks (see [HS16b], [AC18]), we prove a general result and detail examples. These examples exhibit many different behaviors for a wide variety of ranges, showing the interactions between the trajectories of $\mathbb{X}$ and the ones of $\mathbb{V}$.

This study focuses on the investigation of the antioxidant and anti-inflammatory activity of extracts from Ribes nigrum leaves on BV-2 microglial Wt and Acyl-CoA oxidase 1 deficient (Acox1−/−) cell line models, useful for the investigation of some neurodegenerative disorders. Investigations showed the presence of high quantity of phenolic compounds in this extract, among which flavan-3-ols, flavonols, furanocoumarins, hydroxycinnamates, quercetin, and quercetin derivatives were major components, which are known for their biological activity in various test systems. The MTT test revealed the 0.125 mg/mL concentration of R. nigrum extract as the highest non-toxic. The investigated extract showed high antioxidant activity in chemical-based tests. The antioxidant potential of the R. nigrum leaf extract was furtherly explored using the BV-2 microglial cell line models. Moreover, the extract was found to alter the activity of the main antioxidant enzyme, catalase and fatty acid oxidation enzyme, Acyl-CoA oxidase 1 (ACOX1) as well as the expression of appropriate genes in Wt and Acox1−/− BV-2 microglial cells such as Cat, iNos, Il-1β, Tnf-α, and Abcd1. In Wt cells, the treatment with R. nigrum leaf extract ACOX1 activity was downregulated after 24 hours of treatment, meanwhile the catalase activity remains unchanged. The further treatment leaded to the downregulation of catalase and the upregulation of ACOX1 activity. However, in Acox1−/− cells, which represent a model of oxidative stress, an increase in catalase activity was observed only after 48 hours of treatment, indicating an alternative mode of action of the extract. It was also observed the reduced ROS and NO formation in cells, indicating the pronounced antioxidant capacity of R. nigrum extract in the investigated cell-models.

Maintaining energy balance is essential for survival and health. This physiological function is controlled by the brain, which adapts food intake to energy needs. Indeed, the brain constantly receives a multitude of biological signals that are derived from digested foods or that originate from the gastrointestinal tract, energy stores (liver and adipose tissues) and other metabolically active organs (muscles). These signals, which include circulating nutrients, hormones and neuronal inputs from the periphery, collectively provide information on the overall energy status of the body. In the brain, several neuronal populations can specifically detect these signals. Nutrient‐sensing neurons are found in discrete brain areas and are highly enriched in the hypothalamus. In turn, specialized brain circuits coordinate homeostatic responses acting mainly on appetite, peripheral metabolism, activity and arousal. Accumulating evidence shows that hypothalamic microglial cells located at the vicinity of these circuits can influence the brain control of energy balance. However, microglial cells could have opposite effects on energy balance, that is homeostatic or detrimental, and the conditions for this shift are not totally understood yet. One hypothesis relies on the extent of microglial activation, and nutritional lipids can considerably change it.

Phytosterols, which are produced in plants, are structurally similar to cholesterol. Their basic structures consist of a cyclo pentano-perhydrophenanthrene nucleus composed of 3 hexane rings and of a pentane ring with an alkyl side chain. There are around more than 250 phytosterols and related compounds that have been identified in natural resources. Among them, spinasterol and schottenol, its dihydro analog, are often found in seeds, and consequently in seed oils, and in other botanical parts of some plant families such as Sapotaceae, Cactaceae, and Cucurbitaceae. Spinasterol and/or schottenol has been identified in dietary and cosmetic argan oil, milk thistle seed oil, nigella seed oil, and pumkin seed oil. These phytosterols that have several bioactive properties make them potentially attractive molecules in pharmacology. Their chemical and biochemical features are summarized and the analytical methods used to characterize and analyze these compounds are presented.

Microglia are crucial for brain homeostasis, and dysfunction of these cells is a key driver in most neurodegenerative diseases, including peroxisomal leukodystrophies. In X-linked adrenoleukodystrophy (X-ALD), a neuroinflammatory disorder, very long-chain fatty acid (VLCFA) accumulation due to impaired degradation within peroxisomes results in microglial defects, but the underlying mechanisms remain unclear. Using CRISPR/Cas9 gene editing of key genes in peroxisomal VLCFA breakdown (Abcd1, Abcd2, and Acox1), we recently established easily accessible microglial BV-2 cell models to study the impact of dysfunctional peroxisomal β-oxidation and revealed a disease-associated microglial-like signature in these cell lines. Transcriptomic analysis suggested consequences on the immune response. To clarify how impaired lipid degradation impacts the immune function of microglia, we here used RNA-sequencing and functional assays related to the immune response to compare wild-type and mutant BV-2 cell lines under basal conditions and upon pro-inflammatory lipopolysaccharide (LPS) activation. A majority of genes encoding proinflammatory cytokines, as well as genes involved in phagocytosis, antigen presentation, and co-stimulation of T lymphocytes, were found differentially overexpressed. The transcriptomic alterations were reflected by altered phagocytic capacity, inflammasome activation, increased release of inflammatory cytokines, including TNF, and upregulated response of T lymphocytes primed by mutant BV-2 cells presenting peptides. Together, the present study shows that peroxisomal β-oxidation defects resulting in lipid alterations, including VLCFA accumulation, directly reprogram the main cellular functions of microglia. The elucidation of this link between lipid metabolism and the immune response of microglia will help to better understand the pathogenesis of peroxisomal leukodystrophies.

Recently, the study of the protective powers of medicinal plants has become the focus of several studies. Attention has been focused on the identification of new molecules with antioxidant and chelating properties to counter reactive oxygen species (ROS) involved as key elements in several pathologies. Considerable attention is given to argan oil (AO) and olive oil (OO) due to their particular composition and preventive properties. Our study aimed to determine the content of AO and OO on phenolic compounds, chlorophylls, and carotenoid pigments and their antioxidant potential by FRAP and DPPH tests. Thus, several metallic elements can induce oxidative stress, as a consequence of the formation of ROS. Iron is one of these metal ions, which participates in the generation of free radicals, especially OH from H2O2 via the Fenton reaction, initiating oxidative stress. To study the antioxidant potential of AO and OO, we evaluated their preventives effects against oxidative stress induced by ferrous sulfate (FeSO4) in the protozoan Tetrahymena pyriformis and mice. Then, we evaluated the activities of the enzymatic (superoxide dismutase (SOD), glutathione peroxidase (GPx)) and metabolite markers (lipid peroxidation (MDA) and glutathione (GSH)) of the antioxidant balance. The results of the antioxidant compounds show that both oils contain phenolic compounds and pigments. Moreover, AO and OO exhibit antioxidant potential across FRAP and DPPH assays. On the other hand, the results in Tetrahymena pyriformis and mice show a variation in the level of iron-changed SOD and GPx activities and MDA and GSH levels. By contrast, treating Tetrahymena pyriformis and mice with argan and olive oils shows significant prevention in the SOD and GPx activities. These results reveal that the iron-changed ROS imbalance can be counteracted by AO and OO, which is probably related to their composition, especially their high content of polyphenols, sterols, and tocopherols, which is underlined by their antioxidant activities.

Microglial cells ensure essential roles in brain homeostasis. In pathological condition, microglia adopt a common signature, called disease-associated microglial (DAM) signature, characterized by the loss of homeostatic genes and the induction of disease-associated genes. In X-linked adrenoleukodystrophy (X-ALD), the most common peroxisomal disease, microglial defect has been shown to precede myelin degradation and may actively contribute to the neurodegenerative process. We previously established BV-2 microglial cell models bearing mutations in peroxisomal genes that recapitulate some of the hallmarks of the peroxisomal β-oxidation defects such as very long-chain fatty acid (VLCFA) accumulation. In these cell lines, we used RNA-sequencing and identified large-scale reprogramming for genes involved in lipid metabolism, immune response, cell signaling, lysosome and autophagy, as well as a DAM-like signature. We highlighted cholesterol accumulation in plasma membranes and observed autophagy patterns in the cell mutants. We confirmed the upregulation or downregulation at the protein level for a few selected genes that mostly corroborated our observations and clearly demonstrated increased expression and secretion of DAM proteins in the BV-2 mutant cells. In conclusion, the peroxisomal defects in microglial cells not only impact on VLCFA metabolism but also force microglial cells to adopt a pathological phenotype likely representing a key contributor to the pathogenesis of peroxisomal disorders.

We study a simple random walk on Z 2 with constraints on the axes. Motivation comes from physics when particles (a gas for example) are submitted to a local field. In our case we assume that a particle evolves freely in the cones but when touching the axes a force pushes it back progressively to the origin. The main result proves that this force can be parametrized in such a way that a renewal structure appears in the trajectory of the random walk. This implies the existence of an ergodic result for the parts of the trajectory restricted to the axes.

Oxidative stress and inflammation are the key players in neuroinflammation, in which microglia dysfunction plays a central role. Previous studies suggest that argan oil attenuates oxidative stress, inflammation, and peroxisome dysfunction in mouse brains. In this study, we explored the effects of two major argan oil (AO) phytosterols, Schottenol (Schot) and Spinasterol (Spina), on oxidative stress, inflammation, and peroxisomal dysfunction in two murine microglial BV-2 cell lines, wild-ype (Wt) and Acyl-CoA oxidase 1 (Acox1)-deficient cells challenged with LPS treatment. Herein, we used an MTT test to reveal no cytotoxicity for both phytosterols with concentrations up to 5 µM. In the LPS-activated microglial cells, cotreatment with each of these phytosterols caused a significant decrease in intracellular ROS production and the NO level released in the culture medium. Additionally, Schot and Spina were able to attenuate the LPS-dependent strong induction of Il-1β and Tnf-α mRNA levels, as well as the iNos gene and protein expression in both Wt and Acox1−/− microglial cells. On the other hand, LPS treatment impacted both the peroxisomal antioxidant capacity and the fatty acid oxidation pathway. However, both Schot and Spina treatments enhanced ACOX1 activity in the Wt BV-2 cells and normalized the catalase activity in both Wt and Acox1−/− microglial cells. These data suggest that Schot and Spina can protect cells from oxidative stress and inflammation and their harmful consequences for peroxisomal functions and the homeostasis of microglial cells. Collectively, our work provides a compelling argument for the protective mechanisms of two major argan oil phytosterols against LPS-induced brain neuroinflammation.