Stress-related Diseases Research Articles

Antioxidant Carbon Dots Nanozymes Alleviate Stress-induced Depression by Modulating Gut Microbiota.

Depression is a debilitating mental illness that severely threatens millions of individuals and public health. Because of the multifactorial etiologies, there is currently no cure for depression; thus, it is urgently imperative to find alternative antidepressants and strategies. Growing evidence underscores the prominent role of oxidative stress as key pathological hallmarks of depression, making oxidative stress a potential therapeutic target. In this study, we report a N-doped carbon dot nanozyme (CDzyme) with excellent antioxidant capacity for treating depression by remodeling redox homeostasis and gut microbiota. The CDzymes prepared via microwave-assisted fast polymerization of histidine and glucose exhibit superior biocompatibility. Benefiting from the unique structure, CDzymes can provide abundant electrons, hydrogen atoms, and protons for reducing reactions, as well as catalytic sites to mimic redox enzymes. These mechanisms collaborating endow CDzymes with broad-spectrum antioxidant capacity to scavenge reactive oxygen and nitrogen species (•OH, O2-•, H2O2, ONOO-), and oxygen/nitrogen centered free radicals. A depression animal model was established by chronic unpredictable mild stress (CUMS) to evaluate the therapeutic efficacy of CDzymes from the behavioral, physiological, and biochemical index and intestinal flora assessments. CDzymes can remarkably improve depression-like behaviors and key neurotransmitters produced in hippocampus tissues and restore the gut microbiota compositions and the amino acid metabolic functions, proving the potential in treating depression through the intestinal-brain axis system. This study will facilitate the development of intestinal flora dysbiosis nanomedicines and treatment strategies for depression and other oxidative stress related multifactorial diseases.

Transcriptome analysis of rats with chronic unpredictable mild stress treated with electroacupuncture.

Depression remains one of the most prevalent psychiatric disorders, with many patients not responding adequately to available treatments. Electroacupuncture (EA), a nonpharmacologic therapy, holds great promise for alleviating depressive symptoms. In this study, RNA sequencing (RNA-Seq) was used to identify genome-wide alterations in the hippocampus of rats after chronic unpredictable mild stress (CUMS) and EA treatments to further elucidate the mechanism by which EA ameliorates depression to provide a basis for the clinical application of EA in stress-related diseases. The sucrose preference test (SPT), open field test (OFT), and forced swimming test (FST) were used to investigate the ability of EA at Baihui (GV20) and Taichong acupoints (LR3) to improve depression-like behavior in rats subjected to CUMS. Subsequently, RNA-Seq analysis revealed transcriptomic profiles of the hippocampus of rats subjected to CUMS in which EA ameliorated depressive behavior. Finally, the expression profiles of major differentially expressed genes were tested by real-time quantitative polymerase chain reaction (qRT-PCR) to determine the accuracy of the RNA-Seq results. Rats subjected to CUMS exhibited depressive-like behaviors, such as decreased sucrose consumption in the SPT (p<.001), decreased time in the central area of the OFT (p<.001), and increased immobility in the FST (p<.01). Importantly, rats subjected to CUMS and treated with EA showed increased sucrose consumption (p<.001), increased time spent in the central area of the OFT (p<.001) and decreased immobility in the FST (p<.01). Sixty-three genes that were differentially expressed following CUMS were altered by EA; most of these were associated with immune pathways. Compared with those in the control group, the expression levels of Colla2 (p<.001), Col3a1 (p<.001), Psmb9 (p<.01), and Tap1 (p<.01) in the hippocampus of rats subjected to CUMS were lower. The changes in the expression of these genes were reversed by EA treatment. EA at GV20 and LR3 attenuated CUMS-induced depression-like behaviors by regulating the expression of specific genes such as Colla2, Col3a1, Psmb9, and Tap1.

Effects and medical application of plant-origin polyphenols: A narrative review

The impact of oxidative stress in the pathogenesis of various diseases is well known. Oxidative stress occurs when there is an imbalance between the production of reactive oxygen species (ROS) and the ability of a biological system to detoxify these reactive intermediates or repair the resulting damage. Polyphenols, a diverse group of compounds with antioxidant properties, help reduce damage by ROS. They are abundant in fruits, vegetables, tea, coffee, wine, and other plant-based foods. The mechanisms of their antioxidant activity are related to their ability to regulate cellular signaling pathways, metal chelation, and mitochondrial protection, while modulating antioxidant enzyme activity and exhibiting anti-inflammatory effects. Polyphenols can also reduce oxidative stress through ROS scavenging, direct neutralization, or enhancing antioxidant defenses within cells. It has been established that polyphenols derived from plant compounds do not harm the metabolism of normal cells, but are involved in modulating the metabolic pathways of diseased cells, which is related to their high redox sensitivity. Incorporating polyphenol-rich foods into the diet is beneficial for maintaining overall health and reducing the risk of oxidative stress-related diseases. Researchers are exploring the therapeutic potential of polyphenols as dietary supplements or functional foods in medical applications. This review discusses the origin, structure, benefits, and application of plant polyphenols in medicine and the food industry. Keywords: biologically active compounds, polyphenols, oxidative stress, antioxidant activity, functional food.

Unraveling the Relationship Between Vitamin D and Oxidative Stress: A Cross-Sectional Study.

Vitamin D, beyond bone metabolism, has played a significant role in various physiological processes, including modulation of oxidative stress and maintenance of vascular architecture. Oxidative stress, a state of altered balance between reactive oxygen species (ROS) and antioxidants, is a critical factor in the pathogenesis of various chronic diseases. Our study aims to explore the intricate relationship between serum vitamin D levels and markers of oxidative stress in normotensive and hypertensive individuals. A total of 108 age-matched participants (35 to 50 years) of both genders (54 males and 54 females) were included in this cross-sectional study according to the study design and assessed for their serum vitamin D level by using enzyme-linked immunosorbent assay (ELISA) method and serum malondialdehyde (MDA) level by using a spectrophotometer at 540 nm after measurement of the blood pressure. The data were entered in a Microsoft Excel sheet and analyzed using Statistical Package for Social Science (SPSS) software version 20. Our findings demonstrate a significant inverse correlation between serum vitamin D levels and MDA (r = -0.71, p < 0.001), indicating lower lipid peroxidation with higher vitamin D levels. Our study concludes by evident higher serum vitamin D levels associated with reduced oxidative stress, reflected by lower MDA. These findings suggest a potential protective role of vitamin D against oxidative damage, which could have implications for the prevention of oxidative stress-related diseases.

Prophylactic supplementation with selenium nanoparticles protects against foodborne toxin zearalenone-induced intestinal barrier dysfunction

Selenium nanoparticles (SeNPs) have been used as a potential alternative to other forms of selenium in nutritional supplements for the treatment and prevention of inflammatory and oxidative stress-related diseases. Zearalenone (ZEA) is a foodborne mycotoxin present in grains that poses a health threat. Here, we investigated the adverse impacts of ZEA on intestinal homeostasis and explored the protective effects of probiotic-synthesized SeNPs against its damage. Results showed that ZEA reduced mucin and tight junction proteins expression in jejunum, induced inflammatory process and oxidative stress which in turn increased intestinal permeability in mice. ZEA-induced intestinal toxicity was further verified in vitro. Intracellular redox imbalance triggered endoplasmic reticulum (ER) stress in intestinal epithelial cells, which caused structural damage to the ER. Remarkably, SeNPs exhibited a counteractive effect by inducing a decrease in intracellular levels of Inositol 1,4,5-trisphosphate (IP3) and Ca2+, along with a reduction in the expression level of IP3 receptor. SeNPs effectively mitigated ZEA-induced ER stress was related to the increased activity of selenium-dependent antioxidant enzymes and the expression of ER-resident selenoproteins. Furthermore, SeNPs significantly inhibited the activation of PERK/eIF2α/ATF4/CHOP pathway in vitro and in vivo. In addition, SeNPs effectively reversed ZEA-induced gut microbiota dysbiosis and increased the abundance of short-chain fatty acid-producing beneficial bacteria (Alloprevotella and Muribaculaceae). The Spearman correlation analysis suggested that the structure of gut microbiota was closely related to the SeNPs attenuation of ZEA-induced intestinal toxicity. This study provides new insights into ZEA-induced intestinal toxicity and identifies a novel potential nutrient SeNPs to overcome adverse effects.

Phytochemical composition, antioxidant activity, and cytotoxicity of the aqueous extracts of Dracaena arborea and Bridelia ferruginea: In vitro and in silico studies

Dracaena arborea (DA) and Bridelia ferruginea (BF) are medicinal plants used in the treatment of various ailments such as diabetes, infertility, and sexual dysfunctions. The aim of this work was to characterize these plants chemically and investigate their antioxidant and cytotoxicity in vitro and in silico. The cytotoxicity was determined in PC3, NIH3T3 and BT474 cells, and through hemolysis using erythrocytes. Furthermore, selected compounds from DA and BF were docked against some oxidative stress (Keap1: Kelch-like ECH-associated protein 1 and GST: glutathione S-transferase) and cytotoxicity (PARP10: poly(ADP-ribose) polymerase family member 10 and p90 RSK: p90 ribosomal S6 kinases) proteins to predict the ligand-protein interaction. We found that the total phenolic and flavonoid content in BF was significantly (p < 0.001) higher than that of DA. 16 and 32 phytocompounds were identified in DA and BF, respectively. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS+) free radical scavenging activity, and cupric and ferric reducing power of BF were significantly (p < 0.05–0.001) higher than those of DA. Moreover, the ability of BF to inhibit lipid peroxidation was higher than that of DA. DA dose-dependently decreased the viability of PC3, NIH3T3, and BT474 cells, while BF tended to feed the cells. Drug-Likeness and toxicity prediction of selected compounds found in DA and BF were within the acceptable standards, according to Lipinski's rule. The majority of compounds found in DA and BF exhibited a strong binding affinity with Keap1, GST, PARP10 and p90 RSK, which supports the in vitro results. For instance, Cis-cyclohexane-1,3-diamine from DA showed a binding affinity of -6.73 kcal/mol and interacted with Keap1 through five conventional hydrogen bonds, while Nrf2 (a Keap1 inhibitor) exhibited a binding affinity of -11.82 kcal/mol and interacted with Keap1 via two conventional hydrogen bonds. 1,3-propanediamine, n-methyl identified in BF exhibited a high stability with Keap1 (-5.95 kcal/mol) due to the presence of 6 conventional hydrogen bonds. Among the compounds identified in DA, the best stable ligand interacting with PARP10 was 2-deoxy-alpha-d-ribopyranose (-7.62 kcal/mol), as it was well-matched in the PARP10 pocket through five conventional hydrogen bonds. In parallel, among the compounds present in BF, 2-[(methylamino)methyl]cyclohexanol showed the best binding affinity with PARP10 (-9.80 kcal/mol), which was higher than that of veliparib (-8.26 kcal/mol), used as a reference inhibitor. In conclusion, BF has the possibility to be exploited in the prevention/treatment of oxidative stress-related diseases, while DA could be a potential anticancer agent. This could justify their ethnomedicinal uses.

Effects of Fermentation with Kombucha Symbiotic Culture of Bacteria and Yeasts on Antioxidant Activities, Bioactive Compounds and Sensory Indicators of Rhodiola rosea and Salvia miltiorrhiza Beverages.

Kombucha is a well-known fermented beverage traditionally made from black tea infusion. Recent studies have focused on finding alternative materials to create novel kombucha beverages with various health benefits. In this study, we prepared and evaluated two novel kombucha beverages using Rhodiola rosea and Salvia miltiorrhiza as materials. The effects of fermentation with the residue of these plants on the kombucha were also investigated. The antioxidant activities, total phenolic contents, and concentrations of the bioactive compounds of the kombucha beverages were determined by the Trolox equivalent antioxidant capacity test, ferric-reducing antioxidant power test, Folin-Ciocalteu method, and high-performance liquid chromatography, respectively. The results revealed that the kombucha beverages made with Rhodiola rosea and Salvia miltiorrhiza had strong antioxidant capacities and abundant phenolic contents. Additionally, the kombucha fermented with Rhodiola rosea residue had higher FRAP, TEAC and TPC values than that fermented without residue. On the other hand, the Salvia miltiorrhiza kombucha fermented with residue had similar FRAP and TEAC values but lower TPC values compared to that fermented without residue. The correlation analysis showed that gallic acid, salidroside, and tyrosol were responsible for the antioxidant abilities and total phenolic contents of the Rhodiola rosea kombucha, and salvianolic acid A and salvianolic acid B contributed to the antioxidant abilities of the Salvia miltiorrhiza kombucha. Furthermore, the kombucha fermented with Rhodiola rosea residue had the highest sensory scores among the kombucha beverages studied. These findings suggest that Rhodiola rosea and Salvia miltiorrhiza are suitable for making novel kombucha beverages with strong antioxidant abilities and abundant phenolic contents, which can be used in preventing and managing oxidative stress-related diseases.

Sustainable Solution to Antibiotic Resistance: Pavetta indica-Based Nanomedicine

The escalating global health crisis, characterized by the emergence of antimicrobial-resistant pathogens, necessitates innovative strategies. This study explores the potential of Pavetta indica, a previously underutilized plant, as a multifaceted resource for addressing this critical challenge. A comprehensive phytochemical investigation unveiled a rich repertoire of bioactive compounds within P. indica, including essential metabolites Moisture (9.14%), Crude Protein (10.93%), and Crude Fiber (15.46%). Additionally, significant levels of Calcium, Phosphorus, and Ether Extract were identified, suggesting its potential contribution to a balanced diet and a diverse array of secondary metabolites identified through GC-MS analysis identified diverse bioactive compounds including Dodecanoic acid, Lupeol, and β-D-Glucopyranose among others, highlighting its potential health benefits and paving the way for further research on specific bioactivities. P. indica extract exhibited concentration-dependent ABTS and DPPH scavenging activities, comparable to ascorbic acid. This underscores its potential as a natural antioxidant source to combat oxidative stress-related diseases. Leveraging the bio-reducing capabilities of P. indica extract, we embarked on the green synthesis of silver nanoparticles. P. indica extract successfully synthesized silver nanoparticles, confirmed by UV-Vis spectroscopy (SPR band at 420 nm) and TEM (spherical particles, 25-50 nm). These nanoparticles showed potent antimicrobial activity against Bacillus subtilis, E. coli, and Pseudomonas aeruginosa, comparable to Gentamicin. The synthesized silver nanoparticles demonstrated concentration-dependent antifungal activity against Candida albicans, Aspergillus fumigatus, and Sporothrix schenckii, suggesting their potential as effective antifungal agents. Our findings underscore the significance of exploring underutilized plant resources for developing innovative solutions to pressing global health challenges. By integrating phytochemistry, nanotechnology, and microbiology, this research offers a promising approach to combating antimicrobial resistance. The study's outcomes lay the groundwork for future investigations into the underlying mechanisms of antimicrobial action, optimization of nanoparticle properties, and preclinical evaluation of their therapeutic efficacy.

Acute rimonabant treatment prevents anhedonia and memory loss in rats submitted to mild restraint stress

Stress-related disorders are becoming increasingly common and are often associated with cognitive impairments. Within this context, the endocannabinoid (ECB) system, particularly the type 1 cannabinoid (CB1) receptor, seems to play a decisive role in restoring body homeostasis. There is consistent evidence in the literature that disrupted CB1-mediated neurotransmission can ultimately contribute to stress-related diseases. Therefore, the present study aimed to evaluate the participation of CB1 receptors in the integrity of stress-induced peripheral and behavioral responses. For this purpose, male adult Wistar rats underwent physical restraint (1 h/day, for 7 days), followed by a single administration of rimonabant (CB1 receptor antagonist, 3 mg/Kg, intraperitonial) at the end of stress protocol. Animals were then subjected to evaluation of neuroendocrine responses, behavioral tests and quantification of Iba-1 (microglial) immunoreactivity in the parvocellular subdivisions of the paraventricular nucleus of the hypothalamus (PVN). No effects of restraint stress or rimonabant administration were detected on body mass variation. However, stress significantly increased adrenal relative mass and corticosterone secretion, and reduced thymus relative size. The stress effects on adrenal size and corticosterone plasma levels were absent in rimonabant-treated rats, but the thymus size was further reduced in the restraint-rimonabant group. Restraint stress also induced anhedonia, a depression-like behavior, and reduced object recognition index, indicating memory recovery impairment. Treatment with the CB1 antagonist significantly reversed stress-induced anhedonia and memory deficit. In the PVN, restraint stress reduced the number of Iba-1 positive cells in the medial parvocellular region of vehicle- but not rimonabant-treated animals. Taken together, these results indicate that the acute inhibition of the CB1-mediated endogenous pathway restores stress-induced depression-like behaviors and memory loss, suggesting a role for endocannabinoids in the neuro-immune-endocrine interplay at both peripheral and hypothalamic levels.

Recent developments in the design of functional derivatives of edaravone and exploration of their antioxidant activities.

Edaravone, a pyrazalone derivative, is an antioxidant and free radical scavenger used to treat oxidative stress-related diseases. It is a proven drug to mitigate conditions prevailing to oxidative stress by inhibiting lipid peroxidation, reducing inflammation, and thereby preventing endothelial cell death. In recent years, considerable interest has been given by researchers in the derivatization of edaravone by adding varieties of substituents of versatile steric and functional properties to improve its antioxidant and pharmacological activity. This review accounts all the important methods developed for the derivatization of edaravone and the impacts of the structural modifications on the antioxidant activity of the motif.

Antioxidant activity and inhibitory effects on angiotensin I-converting enzyme and α-glucosidase of trans-p-coumaroyl-secologanoside (comselogoside) and its inclusion complex with β-cyclodextrin. Bioaccessibility during simulated in vitro gastrointestinal digestion.

This study explored the impact of complexing comselogoside (COM) with β-cyclodextrin (β-CD) on antioxidant capacity and investigated its in vitro inhibitory effects against α-glucosidase and angiotensin I-converting enzyme (ACE). The COM: β-CD complex in three molar ratios (1:2, 1:1, and 2:1) showed significantly higher antioxidant activity compared to free COM, assessed by DPPH and ferric reducing power assays. COM exhibited weak to moderate α-glucosidase inhibition (IC50 1221 μM) and notable ACE inhibition (IC50 119.4 μM). Encapsulation improved ACE inhibition notably for the 1:2 and 2:1 M ratios. The cleavage of secoiridoid moiety of COM by β-glucosidase further enhanced ACE inhibition from IC50 of 63.91 to 41.75 μg/mL in the hydrolysed mixture. In vitro gastrointestinal digestion revealed 34–40% bioaccessibility of COM and its β-CD complex. This study demonstrates the potential of encapsulated COM as a functional food or supplement for preventing and treating diabetes, hypertension, and oxidative stress-related diseases.

Nanomedicines Targeting Ferroptosis to Treat Stress-Related Diseases.

Ferroptosis, a unique form of regulated cell death driven by iron-dependent lethal lipid peroxidation, is implicated in various stress-related diseases like neurodegeneration, vasculopathy, and metabolic disturbance. Stress-related diseases encompass widespread medical disorders that are influenced or exacerbated by stress. These stressors can manifest in various organ or tissue systems and have significant implications for human overall health. Understanding ferroptosis in these diseases offers insights for therapeutic strategies targeting relevant pathways. This review explores ferroptosis mechanisms, its role in pathophysiology, its connection to stress-related diseases, and the potential of ferroptosis-targeted nanomedicines in treating conditions. This monograph also delves into the engineering of ferroptosis-targeted nanomedicines for tackling stress-related diseases, including cancer, cardia-cerebrovascular, neurodegenerative, metabolic and inflammatory diseases. Anyhow, nanotherapy targeting ferroptosis holds promise by both promoting and suppressing ferroptosis for managing stress-related diseases.

Adenosine protects cardiomyocytes against acrolein-induced cardiotoxicity by enhancing mitochondrial homeostasis, antioxidant defense, and autophagic flux via ERK-activated FoxO1 upregulation

Acrolein is a ubiquitous gaseous air pollutant and endogenous toxicant, which poses strong risk for oxidative stress-related diseases such as cardiovascular disease. Adenosine has been identified as potential therapeutic agent for age-related cardiovascular disease, while the molecular mechanisms underlying its cardioprotection remain elusive. In the present study, we investigated the myocardial protective effects and the mechanism of adenosine on acrolein-induced toxicity in H9c2 cells and primary neonatal rat cardiomyocytes. We found that acrolein caused apoptosis of cardiomyocytes resulting from oxidative damage, autophagy defect, and mitochondrial dysfunction, as evidenced by loss of mitochondrial membrane potential, impairment of mitochondrial biogenesis, dynamics, and oxidative phosphorylation, decrease of mitochondrial deoxyribonucleic acid (mtDNA) copy number and adenosine 5’-triphosphate (ATP) production. Adenosine pretreatment protected against acrolein-induced cardiotoxicity by maintaining mitochondrial homeostasis, activating the phase II detoxifying enzyme system, promoting autophagic flux, and alleviating mitochondrial-dependent apoptosis. We further demonstrated that the up-regulation of forkhead box protein O1 (FoxO1) mediated by extracellular regulated protein kinases (ERK) activation contributes to the cardioprotection of adenosine. These results expand the application of adenosine in cardioprotection to preventing myocardial damages induced by environmental pollutant acrolein exposure, and uncover the adenosine-ERK-FoxO1 axis as the underlying mechanism mediating the protection of mitochondrial homeostasis, Nrf2-mediated antioxidant defense and autophagic flux, shedding light on the better understanding about the pathological mechanism of cardiovascular disease caused by environmental pollutants and applications of adenosine in cardioprotection.

Anti-oxidant, anti-inflammatory and antimicrobial activity of aqueous extract from acerola and amla.

Amla, scientifically known as emblica officinalis and Acerola (malphigian emarginata) both are Vitamin C fruits possess varied medicinal properties being used for preventive disease health management strategies. Therefore, it is of interest to explore the antioxidant, anti-inflammatory, antibacterial, and cytotoxic properties of aqueous extracts from Acerola and Amla. Hence, the anti-inflammatory activity of Acerola and amla was assessed using the bovine serum albumin denaturation assay (BSA Assay), antioxidant properties were compared using DPPH (2,2-diphenyl-1-picrylhydrazyl) assay. Both extracts antibacterial activities were evaluated through the agar well diffusion technique against oral pathogens and Brine shrimp lethality assay for cytotoxicity. The current research sheds light on natural remedies for oxidative stress-related diseases, inflammatory conditions and bacterial infections, offering promising avenues for disease management and preventive healthcare strategies especially in the treatment of oral health diseases like periodontitis.

Design, synthesis and anti-oxidant activities of novel 1,2,3,4-tetrazine, 1,2,3-triazoles and coumarin derivatives and their nanoparticular encapsulation

Nitrogen-containing heterocyclic compounds are currently used for a number of pharmaceutical and agricultural applications because they have biological activities such as antimicrobial, antiviral, antituberculosis, anticancer, analgesic, antioxidant, anti-inflammatory and antidepressant. 1,2,3,4-Tetrazines and 1,2,3-triazoles are examples of high-nitrogen heterocyclic compounds. Coumarins, on the other hand, are lactones that form a group of oxygenated heterocyclic compounds found in plants. In this article, two analogs of 1,2,3,4-tetrazine, two analogs of 1,2,3-triazole and five analogs of coumarin were designed and synthesized. Their chemical structures were characterized by detecting their FTIR, 1H-NMR, and 13C-NMR (APT) spectra. The antioxidant activities of all synthesized molecules were compared at a fixed concentration (0.25 mg ml−1) using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) method. Molecules 9c and 9e, which showed the highest antioxidant activity, were loaded into PLGA (poly(lactic-co-glycolic) acid) nanoparticles using the oil in water (o/w) single emulsion solvent evaporation method as a model study. Synthesized nanoparticles characterized for particle size, zeta potential, functional groups, morphology, and release properties. Particle size and zeta potential of 9c/NP were determined as 216.1 ± 8.944 nm and −14.1 ± 2.40 mV, respectively. The particle size and zeta potential for 9e/NP were measured as 222.0 ± 12.490 nm and −12.4 ± 1.42 mV respectively. The study results obtained on model nanoparticle systems with elucidated physicochemical properties may have the potential to provide a promising basis for oxidative stress-related diseases in the future.

Bioaffinity Ultrafiltration Combined with HPLC-ESI-qTOF-MS/MS for Screening Potential Bioactive Components from the Stems of Dendrobium fimbriatum and In Silico Analysis.

Dendrobium fimbriatum is a perennial herb, and its stems are high-grade tea and nourishing medicinal materials. Various solvent extracts of D. fimbriatum were evaluated for their anti-inflammatory, anti-acetylcholinesterase (AChE), antioxidant, and anti-α-glucosidase properties. Acetone and EtOAc extracts showed significant antioxidant effects. Acetone, n-hexane, and EtOAc extracts revealed potent inhibition against α-glucosidase. EtOAc, n-hexane, and dichloromethane extracts displayed significant anti-AChE activity. Among the isolated constituents, gigantol, moscatin, and dendrophenol showed potent antioxidant activities in FRAP, DPPH, and ABTS radical scavenging tests. Moscatin (IC50 = 161.86 ± 16.45 μM) and dendrophenol (IC50 = 165.19 ± 13.25 μM) displayed more potent anti-AChE activity than chlorogenic acid (IC50 = 236.24 ± 15.85 μM, positive control). Dendrophenol (IC50 = 14.31 ± 3.17 μM) revealed more efficient anti-NO activity than quercetin (positive control, IC50 = 23.09 ± 1.43 μM). Analysis of AChE and iNOS inhibitory components was performed using molecular docking and/or the bioaffinity ultrafiltration method. In bioaffinity ultrafiltration, the binding affinity of compounds to the enzyme (acetylcholinesterase and inducible nitric oxide synthase) was determined using the enrichment factor (EF). Among the main components of the EtOAc extract from D. fimbriatum stem, moscatin, dendrophenol, gigantol, and batatasin III with acetylcholinesterase exhibited the highest binding affinities, with affinity values of 66.31%, 59.48%, 54.60%, and 31.87%, respectively. Moreover, the affinity capacity of the identified compounds with inducible nitric oxide synthase can be ranked as moscatin (88.99%) > dendrophenol (65.11%) > gigantol (44.84%) > batatasin III (27.18%). This research suggests that the bioactive extracts and components of D. fimbriatum stem could be studied further as hopeful candidates for the prevention or treatment of hyperglycemia, oxidative stress-related diseases, and nervous disorders.

"Why (Zebra)fish May Get Ulcers": Cognitive and Social Modulation of Stress in Fish.

In the bestseller book "Why Zebras Don't Get Ulcers", Robert Sapolsky argues that animals do not suffer from stress-related diseases like humans because for them, stress is episodic, while humans in contrast suffer from chronic psychological stress. In particular, the idea that fish cannot experience psychological stress is still prevalent, partly due to the lack of a homologous brain area to the neocortex. However, emerging evidence suggests that teleosts can undergo psychological stress, defined as a subjective and perceptual experience of the stressor, and in recent years, the underlying mechanisms started to be unveiled. The occurrence of cognitive appraisal in the assessment of stressors has been demonstrated in fish, indicating that the subjective evaluation of stimulus valence and salience, rather than absolute intrinsic characteristics of the stimulus itself, play a key role in the activation of the stress response. Moreover, individual biases (i.e., cognitive bias) in the cognitive appraisal of stimuli have also been described in fish, with some individuals consistently evaluating ambiguous stimuli as positive (aka optimists) whereas other individuals (aka pessimists) appraise them as negative. As a result, optimists and pessimists show consistent differences in stress reactivity and susceptibility/resilience to disease. Finally, social context has also been shown to modulate the response to aversive stimuli with the behavior of conspecifics either buffering or enhancing the response (i.e., social buffering vs. social contagion). Cognitive appraisal of stressors occurs in fish, implying that the stress response is modulated by a subjective and perceptual experience of the stressor. Moreover, interindividual consistent cognitive biases in the appraisal of stressors are also present in fish making some individuals more susceptible to stress-related diseases. Therefore, psychological stress has a health toll in fish, and psychologically stressed fish can potentially have ulcers.

Exploring the antimicrobial and antioxidant properties of Lentzea flaviverrucosa strain E25-2 isolated from Moroccan forest soil.

The alarming rise in antimicrobial resistance (AMR) has created a significant public health challenge, necessitating the discovery of new therapeutic agents to combat infectious diseases and oxidative stress-related disorders. The Lentzea flaviverrucosa strain E25-2, isolated from Moroccan forest soil, represents a potential avenue for such research. This study aimed to identify the isolate E25-2, obtained from soil in a cold Moroccan ecosystem, and further investigate its antimicrobial and antioxidant activities. Phylogenetic analysis based on 16S rRNA gene sequences revealed the strain's classification within the Lentzea genus, with a sequence closely resembling that of Lentzea flaviverrucosa AS4.0578 (96.10% similarity). Antimicrobial activity in solid media showed moderate to strong activity against Staphylococcus aureus ATCC 25923, Bacillus cereus strain ATCC 14579, Escherichia coli strain ATCC 25922, Candida albicans strain ATCC 60193 and 4 phytopathogenic fungi. In addition, ethyl acetate extract of this isolate demonstrated potent antimicrobial activity against 7 clinically multi-drug resistant bacteria. Furthermore, it demonstrated antioxidant activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) free radicals, as well as a significant increase in ferric reducing antioxidant power. A significant positive correlation was observed between antioxidant activities and total content of phenolic compounds (p < 0.0001), along with flavonoids (p < 0.0001). Furthermore, gas chromatography-mass spectrometry (GC-MS) analysis revealed the presence of amines, hydroxyl groups, pyridopyrazinone rings, esters and pyrrolopyrazines. The Lentzea genus could offer promising prospects in the fight against antibiotic resistance and in the prevention against oxidative stress related diseases.

Deciphering the therapeutic actions of Brenania brieyi (Rubiaceae) fractions on oxidoinflammatory anomalies

A decline in the antioxidant network during the inflammatory response plays a critical role in the pathogenesis of numerous diseases. We designed this study to decipher the therapeutic efficacy of Brenania brieyi in reducing oxidative stress caused by the inflammatory response to cotton pellets. Graded doses of methanol and chloroform fractions of B. brieyi (MFBB and CFBB) and indomethacin were administered to Wistar rats for seven days after implanting sterilised cotton pellets (20 mg). Thereafter, biochemical indices of oxidative stress were determined using blood samples taken through cardiac puncture. Furthermore, molecular interactions, drug-likeness, and toxicity features of B. brieyi phytochemicals were also assessed. Compared with the untreated group, the groups treated with MFBB and CFBB had a significant (p &amp;lt; 0.05) decrease in granuloma tissue weight and MDA levels while increasing glutathione levels, SOD, and CAT activities. In addition, a substantial increase in inflammatory-induced changes in antioxidant nutrients, together with a decline in liver enzymes, was obtained in the treated groups. The docking tests revealed that the top-scoring phytoconstituents of B. brieyi, n-hexadecanoic acid, and 9-octadecanoic acid interacted well with catalase, having docking scores of -6.19 and -7.58 kcal/mol, respectively. Moreover, the hits had good oral drug-likeness features and a safe toxicity profile. The findings of the study provide evidence that B. brieyi has antioxidant and anti-inflammatory properties, suggesting that it could be used as an alternative therapy to regulate oxidative stress-related diseases.

Mitochondria-targeted drug delivery system based on tetrahedral framework nucleic acids for bone regeneration under oxidative stress

Oxidative stress is present in many diseases and severely affects tissue reconstruction and regeneration. Many traditional Chinese medicinal monomers have excellent antioxidant effects; however, most cannot target the mitochondria, where oxidative stress is produced. In this study, a mitochondria-targeted antioxidant delivery system based on tetrahedral framework nucleic acids (tFNAs) is developed to combat oxidative stress. Antioxidant quercetin cargoes can be effectively loaded into the tFNA “trucks”, and the trucks are modified with mitochondria-targeting molecules to act as “headlights” to efficiently transport the cargo to the mitochondria. These results confirm that the delivery system can be efficiently loaded with quercetin and target the mitochondria. Both in vitro and in vivo studies confirm that the delivery system resists oxidative stress and inflammatory responses in a diabetic periodontitis model, which suffers from severe oxidative stress. The constructed delivery system delays the destruction of periodontal tissues, and promotes periodontal tissue regeneration. This study provides a new strategy for the efficient and targeted delivery of antioxidants, which is of great significance for the therapy of oxidative stress-related diseases and tissue regeneration.