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1 pages, 143 KB  
Correction
Correction: Wróbel et al. The GPR39 Receptor Plays an Important Role in the Pathogenesis of Overactive Bladder and Corticosterone-Induced Depression. Int. J. Mol. Sci. 2024, 25, 12630
by Jan Wróbel, Paulina Iwaniak, Piotr Dobrowolski, Mirosława Chwil, Ilona Sadok, Tomasz Kluz, Artur Wdowiak, Iwona Bojar, Ewa Poleszak, Marcin Misiek, Łukasz Zapała, Ewa M. Urbańska and Andrzej Wróbel
Int. J. Mol. Sci. 2025, 26(17), 8267; https://doi.org/10.3390/ijms26178267 - 26 Aug 2025
Abstract
In the published manuscript [...] Full article
25 pages, 9525 KB  
Article
The Functional Ingredients of the Combined Extract of Mulberry Leaves and Butterfly Pea Flowers Improve Insomnia, Anxiolytic, Memory-Enhancing, and Antidepressant-like Activities in Stress-Exposed Rats
by Orraya Suna, Jintanaporn Wattanathorn, Supaporn Muchimapura, Wipawee Thukham-mee, Sitthichai Iamsaard and Nongnut Uabundit
Life 2025, 15(8), 1308; https://doi.org/10.3390/life15081308 - 18 Aug 2025
Viewed by 415
Abstract
At present, a novel herbal regimen targeting anti-insomnia, anti-anxiety, cognitive performance, and anti-depression effects is required due to the limitations of the current therapy. Based on the crucial role of oxidative stress in the pathophysiology of stress-related brain disorders, it was hypothesized that [...] Read more.
At present, a novel herbal regimen targeting anti-insomnia, anti-anxiety, cognitive performance, and anti-depression effects is required due to the limitations of the current therapy. Based on the crucial role of oxidative stress in the pathophysiology of stress-related brain disorders, it was hypothesized that the functional ingredient derived from mulberry leaves and butterfly pea flowers, which exhibits potent antioxidant activity, should protect against the disorders just mentioned. Male Wistar rats (180–200 g) were orally administered at doses of 125, 250, and 500 mg/kg BW once daily, 45 min before exposure to a 6-h immobilization stress for 14 days. Behavioral assessments, including sleep, anxiety, spatial memory, and depression, were assessed every 7 days. At the end of the study, corticosterone levels, oxidative stress markers, neurotransmitters, IL-6, BDNF, and neuron density in the prefrontal cortex and hippocampus were measured. The functional ingredients demonstrated anti-insomnia, anxiolytic, memory-enhancing, and antidepressant properties. It also increased neuron density and BDNF and activity of SOD and CAT enzymes, whereas corticosterone, GABA-T, AChE, MAO, IL-6, and MDA levels were reduced. A potential regimen targeting showed the benefits of anti-insomnia, anxiolytic, memory-enhancing, and antidepressant properties. However, further studies regarding the precise underlying mechanism and a clinical trial are essentially required. Full article
(This article belongs to the Section Physiology and Pathology)
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17 pages, 1728 KB  
Article
Effects of Light Wavelength on Broiler Performance, Blood Cell Profiles, Stress Levels, and Tibiotarsi Morphology
by Angela Perretti, Victor J. Oyeniran, Jaelen M. Cherry, Rosemary H. Whittle, Zachary Grider, Alexander H. Nelson, Seong W. Kang, Gisela F. Erf and Shawna L. Weimer
Animals 2025, 15(16), 2372; https://doi.org/10.3390/ani15162372 - 13 Aug 2025
Viewed by 422
Abstract
Lighting influences broiler production, health, and behavior. The objective of this study was to examine the effects of three light wavelengths (White [350–780 nm], Blue [450 nm], and Green [560 nm]) on broiler production, activity, fear, stress, blood cell profiles, and tibiotarsi (tibia) [...] Read more.
Lighting influences broiler production, health, and behavior. The objective of this study was to examine the effects of three light wavelengths (White [350–780 nm], Blue [450 nm], and Green [560 nm]) on broiler production, activity, fear, stress, blood cell profiles, and tibiotarsi (tibia) morphology. Day-of-hatch male broiler chicks (N = 600) were housed in pens (N = 12) with one lighting treatment for 42 days. Body weight and feed consumption were recorded on day (D) 0, 14, 28, and 42, and the feed conversion ratio was calculated. The Tonic Immobility test was used to assess the latency (seconds) to right from the testing cradle (D12 and D33). Blood was drawn for leukocyte and plasma corticosterone concentrations (D21 and D41). Accelerometers were attached at 2 and 5 weeks of age to measure activity. On D41, thermal images of the head were taken to measure surface temperatures (eye and beak), the bursa of Fabricius (bursa) was extracted for relative bursa weight, and the right and left tibias were extracted for tibia morphology. After sampling, the remaining broilers were processed. Activity was greatest in Green light at Week 2 (261.17 ± 8.52 m/s2, p < 0.0001), and activity was lowest in White light at Week 5 (98.99 ± 8.52 m/s2, p < 0.0001). Broilers under Blue light had lower concentrations of lymphocytes (8.62 ± 0.40 × 103 cells/µL, p = 0.01) and T cells (7.16 ± 0.33 × 103 cells/µL, p = 0.008) compared to White light. Breast yields were greatest (26.89 ± 0.13%, p = 0.01) in the White treatments compared to Green and Blue treatments. These results suggest that blue light may negatively impact immune health, while green light increases activity, without decreasing production performance, and white light can improve carcass traits. Therefore, lighting color can be strategically used to target welfare or production goals. Full article
(This article belongs to the Collection Current Advances in Poultry Research)
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17 pages, 1107 KB  
Article
Light Color Influences Incubation Characteristics, Postnatal Growth, and Stress Physiology with a Lack of Expression Changes of Myf5 and Myf6 Genes in Gerze Native Chicken
by Godswill Arinzechukwu Iwuchukwu, Uğur Şen, Hasan Önder, Elif Cilavdaroğlu and Umut Sami Yamak
Animals 2025, 15(16), 2347; https://doi.org/10.3390/ani15162347 - 11 Aug 2025
Viewed by 302
Abstract
Light exposure during incubation can influence hatching characteristics, post-hatch growth, and physiological responses in poultry. This study aimed to evaluate the impact of pre-development exposure to different cold-colored light emitting diode (LED) lights on incubation characteristics, growth performance, stress physiology, and myogenic regulatory [...] Read more.
Light exposure during incubation can influence hatching characteristics, post-hatch growth, and physiological responses in poultry. This study aimed to evaluate the impact of pre-development exposure to different cold-colored light emitting diode (LED) lights on incubation characteristics, growth performance, stress physiology, and myogenic regulatory factors (MRFs) expression level in the slow-growing native Gerze chicken breed. Fertilized eggs were incubated under red, green, white, or dark conditions. The shortest hatch window was observed under red light (42 h), while the dark condition resulted in the longest (84 h) (p < 0.05). White light exposure reduced hatchability compared to the other groups (p < 0.05), whereas green and red lights enhanced both chick weight at hatch and egg-to-chick conversion efficiency (p < 0.001). Chicks incubated under green light exhibited superior body weight during the first four weeks (p < 0.05), but those from the red light group maintained consistently higher weights thereafter (p < 0.05). The highest serotonin levels were detected in chicks from the dark group, while the lowest were associated with green light exposure. Red light exposure was associated with the lowest corticosterone concentrations (p < 0.05). Gene expression analysis revealed no significant differences in MRFs across groups. In conclusion, the spectral level of light during incubation exerts measurable effects on hatch dynamics, post-hatch growth, and hormonal regulation in Gerze chicken. Full article
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9 pages, 588 KB  
Communication
Differential Neuroendocrine Responses and Dysregulation of the Hypothalamic–Pituitary–Adrenal Axis Following Repeated Mild Concussive Impacts and Blast Exposures in a Rat Model
by Rex Jeya Rajkumar Samdavid Thanapaul, Jishnu K. S. Krishnan, Manoj Y. Govindarajulu, Chetan Y. Pundkar, Gaurav Phuyal, Joseph B. Long and Peethambaran Arun
Brain Sci. 2025, 15(8), 847; https://doi.org/10.3390/brainsci15080847 - 8 Aug 2025
Viewed by 353
Abstract
Traumatic brain injury (TBI) remains a significant public health concern, particularly among military personnel and contact sport athletes who are frequently exposed to repeated blast overpressure waves and mild concussive impacts, respectively. While moderate and severe TBIs have been extensively studied, the long-term [...] Read more.
Traumatic brain injury (TBI) remains a significant public health concern, particularly among military personnel and contact sport athletes who are frequently exposed to repeated blast overpressure waves and mild concussive impacts, respectively. While moderate and severe TBIs have been extensively studied, the long-term neuroendocrine consequences of mild, repetitive brain trauma are poorly understood. In this study, we investigated the temporal dynamics of hypothalamic–pituitary–adrenal (HPA) axis dysregulation following repeated mild concussive head impacts and blast exposures using two clinically relevant rodent models. Male Sprague-Dawley rats were subjected to repeated mild concussive impacts using a modified weight drop model or repeated blast exposures using an advanced blast simulator. Plasma levels of adrenocorticotropic hormone (ACTH) and corticosterone were measured on days 1 and 30 post-injuries. Our findings revealed that repeated blast exposures induced elevation of plasma ACTH and corticosterone on days 1 and 30 post-blasts. After the repeated mild concussive impacts, increased plasma levels of corticosterone were observed on days 1 and 30, but ACTH levels were increased only on day 30. This study is among the first to directly compare neuroendocrine outcomes of repeated mild concussive impacts and blast exposures within a unified experimental framework. Our findings demonstrate distinct temporal trajectories of HPA axis dysregulation depending on injury type and highlight plasma levels of ACTH and corticosterone as potential biomarkers of subclinical brain trauma. These insights may inform early diagnostic approaches and therapeutic strategies aimed at mitigating long-term stress-related complications following mild traumatic brain injuries. Full article
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10 pages, 769 KB  
Article
Effect of Exposing Layer Chicken Embryos to Continuous Green Light During Incubation and Vaccination Method on Early Life Basal Stress and Humoral Immune Response
by Jill R. Domel and Gregory S. Archer
Poultry 2025, 4(3), 36; https://doi.org/10.3390/poultry4030036 - 8 Aug 2025
Viewed by 268
Abstract
To determine if exposing embryos to light during incubation affects antibody titer and corticosterone immediately following hatch, we incubated layer eggs and exposed them to light or darkness and vaccinated a subset of each treatment against Newcastle Disease Virus (NDV) using in ovo [...] Read more.
To determine if exposing embryos to light during incubation affects antibody titer and corticosterone immediately following hatch, we incubated layer eggs and exposed them to light or darkness and vaccinated a subset of each treatment against Newcastle Disease Virus (NDV) using in ovo administration on ED 18, spray application at hatch (d 0), or not at all. There were six treatments: light incubated and non-vaccinated (LNV), light incubated and in ovo vaccinated (LIV), light incubated and post-hatch vaccinated (LPHV), dark incubated and non-vaccinated (DNV), dark incubated and in ovo-vaccinated (DIV), and dark incubated and post-hatch vaccinated (DPHV). Plasma corticosterone (CORT) and NDV antibody titers were measured on d 0, 7, and 14. Light-incubated chicks had lower (p < 0.05) plasma CORT on d 0. NDV titers did not differ (p > 0.05) between light- and dark-incubated chicks on d 0, 7, or 14. However, LIV chicks had higher antibody titers than LPHV on d 14. Exposing embryos to continuous green light during incubation may reduce stress during the early post-hatch period. Vaccination method, rather than exposure to continuous green light during incubation, may have a greater impact on humoral immune response post-hatch. Full article
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24 pages, 2128 KB  
Article
Central Insulin-Like Growth Factor-1-Induced Anxiolytic and Antidepressant Effects in a Rat Model of Sporadic Alzheimer’s Disease Are Associated with the Peripheral Suppression of Inflammation
by Joanna Dunacka, Beata Grembecka and Danuta Wrona
Cells 2025, 14(15), 1189; https://doi.org/10.3390/cells14151189 - 1 Aug 2025
Viewed by 641
Abstract
(1) Insulin-like growth factor-1 (IGF-1) is a neurotrophin with anti-inflammatory properties. Neuroinflammation and stress activate peripheral immune mechanisms, which may contribute to the development of depression and anxiety in sporadic Alzheimer’s disease (sAD). This study aims to evaluate whether intracerebroventricular (ICV) premedication with [...] Read more.
(1) Insulin-like growth factor-1 (IGF-1) is a neurotrophin with anti-inflammatory properties. Neuroinflammation and stress activate peripheral immune mechanisms, which may contribute to the development of depression and anxiety in sporadic Alzheimer’s disease (sAD). This study aims to evaluate whether intracerebroventricular (ICV) premedication with IGF-1 in a rat model of streptozotocin (STZ)-induced neuroinflammation can prevent the emergence of anhedonia and anxiety-like behavior by impacting the peripheral inflammatory responses. (2) Male Wistar rats were subjected to double ICVSTZ (total dose: 3 mg/kg) and ICVIGF-1 injections (total dose: 2 µg). We analyzed the level of anhedonia (sucrose preference), anxiety (elevated plus maze), peripheral inflammation (hematological and cytometric measurement of leukocyte populations, interleukin (IL)-6), and corticosterone concentration at 7 (very early stage, VES), 45 (early stage, ES), and 90 days after STZ injections (late stage, LS). (3) We found that ICVIGF-1 administration reduces behavioral symptoms: anhedonia (ES and LS) and anxiety (VES, ES), and peripheral inflammation: number of leukocytes, lymphocytes, T lymphocytes, monocytes, granulocytes, IL-6, and corticosterone concentration (LS) in the rat model of sAD. (4) The obtained results demonstrate beneficial effects of central IGF-1 administration on neuropsychiatric symptoms and peripheral immune system activation during disease progression in the rat model of sAD. Full article
(This article belongs to the Section Cells of the Nervous System)
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24 pages, 1438 KB  
Article
Neonatal Handling Positively Modulates Anxiety, Sensorimotor Gating, Working Memory, and Cortico-Hippocampal Neuroplastic Adaptations in Two Genetically Selected Rat Strains Differing in Emotional and Cognitive Traits
by Cristóbal Río-Álamos, Maria P. Serra, Francesco Sanna, Maria A. Piludu, Marianna Boi, Toni Cañete, Daniel Sampedro-Viana, Ignasi Oliveras, Adolf Tobeña, Maria G. Corda, Osvaldo Giorgi, Alberto Fernández-Teruel and Marina Quartu
Brain Sci. 2025, 15(8), 776; https://doi.org/10.3390/brainsci15080776 - 22 Jul 2025
Viewed by 440
Abstract
Background/Objectives: The bidirectional selection of the Roman low- (RLA) and Roman high-avoidance (RHA) rat strains for extremely slow vs. very rapid acquisition of the two-way (shuttle-box) avoidance response has generated two divergent phenotypic profiles: RHA rats exhibit a behavioural pattern and gene [...] Read more.
Background/Objectives: The bidirectional selection of the Roman low- (RLA) and Roman high-avoidance (RHA) rat strains for extremely slow vs. very rapid acquisition of the two-way (shuttle-box) avoidance response has generated two divergent phenotypic profiles: RHA rats exhibit a behavioural pattern and gene expression profile in the frontal cortex and hippocampus (HPC) that are relevant to social and attentional/cognitive schizophrenia-linked symptoms; on the other hand, RLA rats display phenotypic traits linked to increased anxiety and sensitivity to stress-induced depression-like behaviours. The present studies aimed to evaluate the enduring and potentially positive effects of neonatal handling-stimulation (NH) on the traits differentiating these two strains of rats. Methods: We evaluated the effects of NH on anxious behaviour, prepulse inhibition of startle (PPI), spatial working memory, and hormone responses to stress in adult rats of both strains. Furthermore, given the proposed involvement of neuronal/synaptic plasticity and neurotrophic factors in the development of anxiety, stress, depression, and schizophrenia-related symptoms, using Western blot (WB) we assessed the effects of NH on the content of brain-derived neurotrophic factor (BDNF), its trkB receptor and Polysialilated-Neural Cell Adhesion Molecule (PSA-NCAM), in the prefrontal cortex (PFC), anterior cingulate cortex (ACg), ventral (vHPC), and dorsal (dHPC) hippocampus of adult rats from both strains. Results: NH increased novelty-induced exploration and reduced anxiety, particularly in RLA rats, attenuated the stress-induced increment in corticosterone and prolactin plasma levels, and improved PPI and spatial working memory in RHA rats. These effects correlated to long-lasting increases of BDNF and PSA-NCAM content in PFC, ACg, and vHPC. Conclusions: Collectively, these findings show enduring and distinct NH effects on neuroendocrine and behavioural and cognitive processes in both rat strains, which may be linked to neuroplastic and synaptic changes in the frontal cortex and/or hippocampus. Full article
(This article belongs to the Section Behavioral Neuroscience)
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29 pages, 15117 KB  
Article
Reduction in SH-SY5Y Cell Stress Induced by Corticosterone and Attenuation of the Inflammatory Response in RAW 264.7 Cells Using Endomorphin Analogs
by Renata Perlikowska, Angelika Długosz-Pokorska, Małgorzata Domowicz, Sylwia Grabowicz, Mariusz Stasiołek and Małgorzata Zakłos-Szyda
Biomedicines 2025, 13(7), 1774; https://doi.org/10.3390/biomedicines13071774 - 20 Jul 2025
Viewed by 631
Abstract
Background: To identify drug candidates that reduce cellular stress, linear peptides known as endomorphin (EM) analogs containing proline surrogates in position 2 were tested in in vitro injury models induced by corticosterone (CORT). Methods: In this study, neuroblastoma (SH-SY5Y) cells were treated with [...] Read more.
Background: To identify drug candidates that reduce cellular stress, linear peptides known as endomorphin (EM) analogs containing proline surrogates in position 2 were tested in in vitro injury models induced by corticosterone (CORT). Methods: In this study, neuroblastoma (SH-SY5Y) cells were treated with CORT and synthesized peptides, and then the cell viability and morphology, reactive oxygen species production (ROS), mitochondrial membrane potential (ΔΨm), adenosine triphosphate (ATP), and intracellular calcium ion [Ca2+]i levels were evaluated. We also conducted an in-depth analysis of the apoptosis markers using quantitative real-time PCR (qPCR). Finally, we explore the brain-derived neurotrophic factor (BDNF) expression (qPCR) and protein levels (ELI-SA and Western blot). Results: The strongest neuroprotective effect in the CORT-induced stress model was shown by peptide 3 and peptide 7 (in the following sequence Tyr-Inp-Trp-Phe-NH2 and Tyr-Inp-Phe-Phe-NH2, respectively). These peptides significantly improved cell viability and reduced oxidative stress in CORT-treated cells. Conclusions: Their neuroprotective potential appears linked to anti-apoptotic effects, along with in-creased BDNF expression. Moreover, in the lipopolysaccharide (LPS)- and interferon-γ (IFN-γ)-induced damage model in macrophage RAW 264.7 cells, these two peptides reduced the secretion of inflammatory mediators nitric oxide (NO), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). Peptides exhibiting both neuroprotective and anti-inflammatory properties warrant further investigation as potential therapeutic agents. Full article
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17 pages, 5091 KB  
Article
Immunomodulatory Effects of Cucurbita pepo L. Extract in Chronic Stress-Induced Dysregulation of Lymphoid Organs in Rats
by Safa H. Qahl, Hailah M. Almohaimeed, Sami A. Algaidi, Ashwaq H. Batawi, Zuhair M. Mohammedsaleh, Tarek Hamdy Abd-Elhamid, Nawal H. Almohammadi, Nasra N. Ayuob and Amany Refaat Mahmoud
Pharmaceuticals 2025, 18(7), 1046; https://doi.org/10.3390/ph18071046 - 17 Jul 2025
Viewed by 519
Abstract
Objectives: Recently, increased attention has been given to pumpkin due to its proved nutritional components, which include antioxidant, antifatigue, and anti-inflammatory effects. The aim of the present work was to assess the impact of Cucurbita pepo L. (CP) on chronic [...] Read more.
Objectives: Recently, increased attention has been given to pumpkin due to its proved nutritional components, which include antioxidant, antifatigue, and anti-inflammatory effects. The aim of the present work was to assess the impact of Cucurbita pepo L. (CP) on chronic unpredictable mild stress (CUMS)-induced changes in lymphoid organs through evaluating its effect on the histological structure of spleen, thymus gland, and lymph nodes compared to the antidepressant fluoxetine (FLU). Materials and Methods: Fifty male albino rats equally distributed into five groups that included control, control + CP, CUMS-exposed, FLU-treated, and CP-treated groups were used in this study. Rats were exposed to CUMS for 4 weeks, and treatment (either with FLU or CP) was started after 14 days of exposure. Behavior of the rats, serum corticosterone, oxidants/antioxidants profile, proinflammatory cytokines, and gene expression of glucocorticoid receptor (GR) and β-adrenergic receptor (β2-AR) were assessed after 28 days. Spleen, thymus gland, and lymph nodes were histopathologically assessed. Results: CP administration significantly reduced the CUMS-induced behavioural changes evident by the significant reduction in immobility time (p = 0.02) and corticosterone level (p < 0.001). Biochemically, CP reduced TNF-α and IL-6 (p < 0.001) and markedly alleviated the changes in oxidants/antioxidants in the serum and lymphoid organs compared to fluoxetine. CP significantly (p < 0.001) reduced CUMS-induced changes in GR and (β2-AR). Histopathologically, CP alleviated changes observed in the spleen, lymph nodes, and thymus gland. It significantly reduced the number of CD4, CD8, CD68, CD20, and caspase-3 immunopositive cells in the studied organs. Conclusions: This study proved the potential efficacy of CP in alleviating depression-associated immunodysregulation either alone or in combination with antidepressant therapy. Full article
(This article belongs to the Section Pharmacology)
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25 pages, 689 KB  
Article
Bioactive Properties and Phenolic Profile of Bioaccessible and Bioavailable Fractions of Red Radish Microgreens After In Vitro Digestion
by Dorota Sosnowska, Małgorzata Zakłos-Szyda, Dominika Kajszczak and Anna Podsędek
Molecules 2025, 30(14), 2976; https://doi.org/10.3390/molecules30142976 - 15 Jul 2025
Viewed by 322
Abstract
The health-promoting activity of radish microgreens after consumption depends on their bioaccessibility and bioavailability. In this study, we compared the composition of phenolic compounds, their cytoprotective and anti-inflammatory activities in cell lines, and antioxidant properties of the undigested radish microgreens with their fractions [...] Read more.
The health-promoting activity of radish microgreens after consumption depends on their bioaccessibility and bioavailability. In this study, we compared the composition of phenolic compounds, their cytoprotective and anti-inflammatory activities in cell lines, and antioxidant properties of the undigested radish microgreens with their fractions obtained after simulated in vitro digestion in the stomach, as well as in the small and large intestine. The results have demonstrated higher levels of total phenolics (by 70.35%) and total hydroxycinnamic acids (3.5 times increase), an increase in scavenging efficiency toward ABTS•+ and superoxide anion radicals, and an increase in the reduction potential (FRAP method) in the gastric bioaccessible fraction. In contrast, small intestinal digestion negatively affected phenolic content (a reduction of 53.30–75.63%), except for total hydroxycinnamic acids (3-fold increase). Incubation of the non-bioavailable fraction with bacterial enzymes led to further degradation. Undigested microgreens had no negative impact on Caco-2, HT-29, and SH-SY5Y cells’ metabolism at 0.05–2 mg/mL, while all digested samples at 1 mg/mL revealed their cytotoxic potential. All samples used at a non-cytotoxic concentration showed protective activity against H2O2 and corticosterone-induced oxidative stress generation as well as reduced proinflammatory cytokines production. Overall, radish microgreens may exhibit a broad spectrum of biological activities when consumed. Full article
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22 pages, 5061 KB  
Article
Urolithin A Exhibits Antidepressant-like Effects by Modulating the AMPK/CREB/BDNF Pathway
by Yaqian Di, Rui Xue, Xia Li, Zijia Jin, Hanying Li, Lanrui Wu, Youzhi Zhang and Lei An
Nutrients 2025, 17(14), 2294; https://doi.org/10.3390/nu17142294 - 11 Jul 2025
Viewed by 766
Abstract
Background/Objectives: Urolithin A (UA), a gut-derived metabolite of ellagitannins or ellagic acid, has recently gained attention for its potential benefits to brain health. The present research aimed to assess the antidepressant-like properties of UA in both in vitro and in vivo models and [...] Read more.
Background/Objectives: Urolithin A (UA), a gut-derived metabolite of ellagitannins or ellagic acid, has recently gained attention for its potential benefits to brain health. The present research aimed to assess the antidepressant-like properties of UA in both in vitro and in vivo models and explored the molecular mechanisms underlying these effects. Methods: We investigated the antidepressant effects and mechanisms of UA in a model of corticosterone-induced damage to PC12 cells and in a model of chronic socially frustrating stress. Results: Our results demonstrate that UA treatment (5 and 10 μM) significantly alleviated cellular damage and inflammation in corticosterone (CORT)-treated PC12 cells. Furthermore, UA administration (50 and 100 mg/kg) significantly reduced immobility time in the mouse tail suspension test (TST) and forced swim test (FST), indicating its antidepressant-like activity. Additionally, treatment with UA led to the activation of the cAMP response element-binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling cascade and triggered the activation of adenosine monophosphate-activated protein kinase (AMPK) during these processes. Importantly, pretreatment with AMPK-specific inhibitor Compound C abolished UA’s cytoprotective effects in PC12 cells, as well as its behavioral efficacy in the FST and TST, and its neurotrophic effects, highlighting the critical role of AMPK activation in mediating these effects. Furthermore, in the chronic social defeat stress (CSDS) mouse model, UA treatment (50 and 100 mg/kg) significantly alleviated depression-like behaviors, including reduced sucrose preference in the sucrose preference test, increased social avoidance behavior in the social interaction test, and anxiety-like behaviors, including diminished exploration, in the elevated plus maze test, suggesting the antidepressant-like and anxiolytic-like activities of UA. Moreover, UA treatment reversed elevated serum stress hormone levels, hippocampal inflammation, and the decreased AMPK/CREB/BDNF signaling pathway in the hippocampus of CSDS mice. Conclusions: Together, these results provide compelling evidence for UA as a viable dietary supplement or therapeutic option for managing depression. Full article
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14 pages, 1006 KB  
Article
Investigating Systemic Metabolic Effects of Betula alba Leaf Extract in Rats via Urinary Metabolomics
by Gregorio Peron, Alina Yerkassymova, Gokhan Zengin and Stefano Dall’Acqua
Metabolites 2025, 15(7), 471; https://doi.org/10.3390/metabo15070471 - 10 Jul 2025
Viewed by 435
Abstract
Background/Objectives: Herbal extracts from Betula alba (birch) are traditionally used for their purported diuretic effects, but scientific evidence supporting these claims remains limited. In this pilot study, we evaluated the short-term effects of a standardized B. alba leaf extract in healthy adult rats [...] Read more.
Background/Objectives: Herbal extracts from Betula alba (birch) are traditionally used for their purported diuretic effects, but scientific evidence supporting these claims remains limited. In this pilot study, we evaluated the short-term effects of a standardized B. alba leaf extract in healthy adult rats using an untargeted urinary metabolomics approach based on UPLC-QTOF. Methods: Two doses, 25 or 50 mg/kg, of a standardized B. alba extract were orally administered to rats. The extract contains hyperoside (0.53%), quercetin glucuronide (0.36%), myricetin glucoside (0.32%), and chlorogenic acid (0.28%) as its main constituents. After 3 days of treatment, the 24 h urine output was measured. Results: While no statistically significant changes were observed in the 24 h urine volume or the urinary Na+ and K+ excretion, multivariate metabolomic analysis revealed treatment-induced alterations in the urinary metabolic profile. Notably, the levels of two glucocorticoids, i.e., corticosterone and 11-dehydrocorticosterone, were increased in treated animals, suggesting that the extract may influence corticosteroid metabolism or excretion, potentially impacting antidiuretic hormone signaling. Elevated bile-related compounds, including bile acids and bilin, and glucuronidated metabolites were also observed, indicating changes in bile acid metabolism, hepatic detoxification, and possibly gut microbiota activity. Conclusions: Although this study did not confirm a diuretic effect of B. alba extract, the observed metabolic shifts suggest broader systemic bioactivities that warrant further investigation. Overall, the results indicate that the approach based on urinary metabolomics may be valuable in uncovering the mechanisms of action and evaluating the bioactivity of herbal extracts with purported diuretic properties. Full article
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12 pages, 216 KB  
Article
Effects of Dietary Additives on Nitrogen Balance, Odor Emissions, and Yolk Corticosterone in Laying Hens Fed Low-Protein Diets
by Ju-Yong Song, Yun-Ji Heo, Jina Park, Hyun-Kwan Lee, Yoo Bhin Kim, Byung-Yeon Kwon, Da-Hye Kim and Kyung-Woo Lee
Animals 2025, 15(14), 2021; https://doi.org/10.3390/ani15142021 - 9 Jul 2025
Viewed by 367
Abstract
The objective of this study was to evaluate the effects of various feed additives on odor emissions, gut health, and stress responses in laying hens fed low-protein diets. Four commercially available functional feed additives (Bacillus subtilis, protease, saponin, and thyme-based essential [...] Read more.
The objective of this study was to evaluate the effects of various feed additives on odor emissions, gut health, and stress responses in laying hens fed low-protein diets. Four commercially available functional feed additives (Bacillus subtilis, protease, saponin, and thyme-based essential oil) were selected for this study. A total of 288 Hy-Line brown laying hens aged 49 weeks were randomly fed on one of six experiment diets: a 16% standard crude protein diet, a 12% low-crude-protein (LCP) diet, and LCP diets supplemented with Bacillus-based probiotic, protease, saponin, or thyme-based essential oils prepared for 8 weeks. Each treatment had eight replicates with six birds per replicate. Lowering crude protein levels affected the laying performance, nitrogen balance, odor production (i.e., ammonia), and nutrient digestibility but did not alter eggshell quality or fecal short-chain fatty acids. Dietary additives added into the LCP diet did not affect the laying performance, egg qualities, and nitrogen balance but increased crude ash digestibility compared with the LCP-diet-fed laying hens. Branched-chain fatty acids tended to be higher in all laying hens fed low-CP diets, irrespective of feed additives. Notably, low vs. standard protein diets tended to increase yolk corticosterone levels, which is an indicator of stress responses in chickens. This low-CP-mediated increase in yolk corticosterone was partially decreased by 20.8–48.6% on average, depending on the additives used. Our study suggests that low-protein diets could effectively lower nitrogen excretion and odor emissions. However, adding dietary additives into low-protein diets has minimal effects on low-CP-diet-fed laying hens, which needs further studies to clarify the role of low-crude-protein diets and dietary additives in modulating hindgut fermentation via shaping the gut microbiota and stress responses of laying hens. Full article
(This article belongs to the Section Poultry)
19 pages, 6101 KB  
Article
A High-Calorie Diet Aggravates Lipopolysaccharide-Induced Pulmonary Inflammation in Juvenile Rats via Hypothalamic-Pituitary-Adrenal Axis-Related Pathways
by Qianqian Li, Hui Liu, Chen Bai, Lin Jiang, Chen Su, Xueying Qin, Tiegang Liu and Xiaohong Gu
Int. J. Mol. Sci. 2025, 26(14), 6554; https://doi.org/10.3390/ijms26146554 - 8 Jul 2025
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Abstract
The hypothalamic-pituitary-adrenal (HPA) axis plays an important regulatory role in inflammatory responses to systemic or local infection in the host. A high-calorie diet, which can aggravate pediatric pneumonia and delay recovery, is intimately associated with HPA axis disorder; however, its underlying mechanisms remain [...] Read more.
The hypothalamic-pituitary-adrenal (HPA) axis plays an important regulatory role in inflammatory responses to systemic or local infection in the host. A high-calorie diet, which can aggravate pediatric pneumonia and delay recovery, is intimately associated with HPA axis disorder; however, its underlying mechanisms remain unknown. This study examined whether the mechanism by which a high-calorie diet aggravates pneumonia is related to HPA axis disorder. In this study, juvenile rats were fed a high-calorie diet and/or nebulized with lipopolysaccharide (LPS) for model construction. Our data shows that a high-calorie diet increases interleukin-1 beta(IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) levels in lung tissues and aggravates LPS-induced inflammatory injury in the lungs of juvenile rats. Additionally, we found that a high-calorie diet decreases the expression level of serum adrenocorticotropic hormone (ACTH) and corticosterone (CORT) in juvenile rats with pneumonia, resulting in HPA axis disorder. Hypothalamus proteomics and Western blot results proved that a high-calorie diet upregulated the expression level of hypothalamus hypoxia-inducible factor-1 alpha (HIF-1α) in juvenile rats with pneumonia, and this mechanism is associated with reduced HIF-1α ubiquitination. We further observed that HPA axis disorder was significantly abated and inflammatory damage in rat lung tissues was significantly alleviated after in vivo HIF-1α pathway inhibition. This shows that pneumonia aggravation by a high-calorie diet is associated with interference in the HIF-1α-mediated HPA axis. A high-calorie diet boosts HIF-1α signaling in the hypothalamus and exacerbates LPS-induced pneumonia by disrupting the HPA axis. This sheds light on lung inflammation and strengthens the lung-brain connection. Full article
(This article belongs to the Section Molecular Endocrinology and Metabolism)
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