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Search Results (1,333)

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Keywords = RAW264.7 macrophage cells

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16 pages, 2365 KiB  
Article
Surface Charge Affects the Intracellular Fate and Clearance Dynamics of CdSe/ZnS Quantum Dots in Macrophages
by Yuan-Yuan Liu, Yong-Yue Sun, Yuan Guo, Lu-Lu Chen, Jun-Hao Guo and Haifang Wang
Nanomaterials 2025, 15(15), 1189; https://doi.org/10.3390/nano15151189 - 3 Aug 2025
Viewed by 162
Abstract
The biological effects of nanoparticles are closely related to their intracellular content and location, both of which are influenced by various factors. This study investigates the effects of surface charge on the uptake, intracellular distribution, and exocytosis of CdSe/ZnS quantum dots (QDs) in [...] Read more.
The biological effects of nanoparticles are closely related to their intracellular content and location, both of which are influenced by various factors. This study investigates the effects of surface charge on the uptake, intracellular distribution, and exocytosis of CdSe/ZnS quantum dots (QDs) in Raw264.7 macrophages. Negatively charged 3-mercaptopropanoic acid functionalized QDs (QDs-MPA) show higher cellular uptake than positively charged 2-mercaptoethylamine functionalized QDs (QDs-MEA), and serum enhances the uptake of both types of QDs via protein corona-mediated receptor endocytosis. QDs-MEA primarily enter the cells through clathrin/caveolae-mediated pathways and predominantly accumulate in lysosomes, while QDs-MPA are mainly internalized through clathrin-mediated endocytosis and localize to both lysosomes and mitochondria. Exocytosis of QDs-MPA is faster and more efficient than that of QDs-MEA, though both exhibit limited excretion. In addition to endocytosis and exocytosis, cell division influences intracellular QD content over time. These results reveal the charge-dependent interactions between QDs and macrophages, providing a basis for designing biocompatible nanomaterials. Full article
(This article belongs to the Section Biology and Medicines)
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24 pages, 3243 KiB  
Article
Design of Experiments Leads to Scalable Analgesic Near-Infrared Fluorescent Coconut Nanoemulsions
by Amit Chandra Das, Gayathri Aparnasai Reddy, Shekh Md. Newaj, Smith Patel, Riddhi Vichare, Lu Liu and Jelena M. Janjic
Pharmaceutics 2025, 17(8), 1010; https://doi.org/10.3390/pharmaceutics17081010 - 1 Aug 2025
Viewed by 196
Abstract
Background: Pain is a complex phenomenon characterized by unpleasant experiences with profound heterogeneity influenced by biological, psychological, and social factors. According to the National Health Interview Survey, 50.2 million U.S. adults (20.5%) experience pain on most days, with the annual cost of prescription [...] Read more.
Background: Pain is a complex phenomenon characterized by unpleasant experiences with profound heterogeneity influenced by biological, psychological, and social factors. According to the National Health Interview Survey, 50.2 million U.S. adults (20.5%) experience pain on most days, with the annual cost of prescription medication for pain reaching approximately USD 17.8 billion. Theranostic pain nanomedicine therefore emerges as an attractive analgesic strategy with the potential for increased efficacy, reduced side-effects, and treatment personalization. Theranostic nanomedicine combines drug delivery and diagnostic features, allowing for real-time monitoring of analgesic efficacy in vivo using molecular imaging. However, clinical translation of these nanomedicines are challenging due to complex manufacturing methodologies, lack of standardized quality control, and potentially high costs. Quality by Design (QbD) can navigate these challenges and lead to the development of an optimal pain nanomedicine. Our lab previously reported a macrophage-targeted perfluorocarbon nanoemulsion (PFC NE) that demonstrated analgesic efficacy across multiple rodent pain models in both sexes. Here, we report PFC-free, biphasic nanoemulsions formulated with a biocompatible and non-immunogenic plant-based coconut oil loaded with a COX-2 inhibitor and a clinical-grade, indocyanine green (ICG) near-infrared fluorescent (NIRF) dye for parenteral theranostic analgesic nanomedicine. Methods: Critical process parameters and material attributes were identified through the FMECA (Failure, Modes, Effects, and Criticality Analysis) method and optimized using a 3 × 2 full-factorial design of experiments. We investigated the impact of the oil-to-surfactant ratio (w/w) with three different surfactant systems on the colloidal properties of NE. Small-scale (100 mL) batches were manufactured using sonication and microfluidization, and the final formulation was scaled up to 500 mL with microfluidization. The colloidal stability of NE was assessed using dynamic light scattering (DLS) and drug quantification was conducted through reverse-phase HPLC. An in vitro drug release study was conducted using the dialysis bag method, accompanied by HPLC quantification. The formulation was further evaluated for cell viability, cellular uptake, and COX-2 inhibition in the RAW 264.7 macrophage cell line. Results: Nanoemulsion droplet size increased with a higher oil-to-surfactant ratio (w/w) but was no significant impact by the type of surfactant system used. Thermal cycling and serum stability studies confirmed NE colloidal stability upon exposure to high and low temperatures and biological fluids. We also demonstrated the necessity of a solubilizer for long-term fluorescence stability of ICG. The nanoemulsion showed no cellular toxicity and effectively inhibited PGE2 in activated macrophages. Conclusions: To our knowledge, this is the first instance of a celecoxib-loaded theranostic platform developed using a plant-derived hydrocarbon oil, applying the QbD approach that demonstrated COX-2 inhibition. Full article
(This article belongs to the Special Issue Quality by Design in Pharmaceutical Manufacturing)
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15 pages, 1487 KiB  
Article
Protective Effects of a Bifidobacterium-Based Probiotic Mixture on Gut Inflammation and Barrier Function
by Yeji You, Tae-Rahk Kim, Minn Sohn, Dongmin Yoo and Jeseong Park
Microbiol. Res. 2025, 16(8), 168; https://doi.org/10.3390/microbiolres16080168 - 1 Aug 2025
Viewed by 329
Abstract
Disruption of the intestinal epithelial barrier is a key driver of gut-derived inflammation in various disorders, yet strategies to preserve or restore barrier integrity remain limited. To address this, we evaluated a four-strain Bifidobacterium mixture—selected for complementary anti-inflammatory potency and industrial scalability—in lipopolysaccharide [...] Read more.
Disruption of the intestinal epithelial barrier is a key driver of gut-derived inflammation in various disorders, yet strategies to preserve or restore barrier integrity remain limited. To address this, we evaluated a four-strain Bifidobacterium mixture—selected for complementary anti-inflammatory potency and industrial scalability—in lipopolysaccharide (LPS)-challenged RAW 264.7 macrophages and a Caco-2/THP-1 transwell co-culture model. Pretreatment with the probiotic blend reduced nitric oxide (NO) release in a dose-dependent manner by 25.9–48.3% and significantly down-regulated the pro-inflammatory markers in macrophages. In the co-culture system, the formulation decreased these markers, increased transepithelial electrical resistance (TEER) by up to 31% at 105 colony-forming unit (CFU)/mL after 48 h, and preserved the membrane localization of tight junction (TJ) proteins. Adhesion to Caco-2 cells (≈ 6%) matched that of the benchmark probiotic Lacticaseibacillus rhamnosus GG, suggesting direct epithelial engagement. These in vitro findings demonstrate that this probiotic mixture can attenuate LPS-driven inflammation and reinforce epithelial architecture, providing a mechanistic basis for its further evaluation in animal models and clinical studies of intestinal inflammatory disorders. Full article
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19 pages, 10625 KiB  
Article
SZC-6 Promotes Diabetic Wound Healing in Mice by Modulating the M1/M2 Macrophage Ratio and Inhibiting the MyD88/NF-χB Pathway
by Ang Xuan, Meng Liu, Lingli Zhang, Guoqing Lu, Hao Liu, Lishan Zheng, Juan Shen, Yong Zou and Shengyao Zhi
Pharmaceuticals 2025, 18(8), 1143; https://doi.org/10.3390/ph18081143 - 31 Jul 2025
Viewed by 292
Abstract
Background/Objectives: The prolonged M1-like pro-inflammatory polarization of macrophages is a key factor in the delayed healing of diabetic ulcers (DU). SIRT3, a primary mitochondrial deacetylase, has been identified as a regulator of inflammation and represents a promising new therapeutic target for DU [...] Read more.
Background/Objectives: The prolonged M1-like pro-inflammatory polarization of macrophages is a key factor in the delayed healing of diabetic ulcers (DU). SIRT3, a primary mitochondrial deacetylase, has been identified as a regulator of inflammation and represents a promising new therapeutic target for DU treatment. Nonetheless, the efficacy of existing SIRT3 agonists remains suboptimal. Methods: Here, we introduce a novel compound, SZC-6, demonstrating promising activity levels. Results: SZC-6 treatment down-regulated the expression of inflammatory factors in LPS-treated RAW264.7 cells and reduced the proportion of M1 macrophages. Mitosox, IF, and JC-1 staining revealed that SZC-6 preserved cellular mitochondrial homeostasis and reduced the accumulation of reactive oxygen species. In vivo experiments demonstrated that SZC-6 treatment accelerated wound healing in diabetic mice. Furthermore, HE and Masson staining revealed increased neovascularization at the wound site with SZC-6 treatment. Tissue immunofluorescence results indicated that SZC-6 effectively decreased the proportion of M1-like cells and increased the proportion of M2-like cells at the wound site. We also found that SZC-6 significantly reduced MyD88, p-IκBα, and NF-χB p65 protein levels and inhibited the nuclear translocation of P65 in LPS-treated cells. Conclusions: The study concluded that SZC-6 inhibited the activation of the NF-χB pathway, thereby reducing the inflammatory response and promoting skin healing in diabetic ulcers. SZC-6 shows promise as a small-molecule compound for promoting diabetic wound healing. Full article
(This article belongs to the Section Pharmacology)
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22 pages, 1531 KiB  
Article
Evaluation of the Biological Properties and Antibacterial Activities of the Natural Food Supplement “Epavin” for Liver Detoxification and Protection
by Alexia Barbarossa, Maria Pia Argentieri, Maria Valeria Diella, Anita Caforio, Antonio Carrieri, Filomena Corbo, Antonio Rosato and Alessia Carocci
Foods 2025, 14(15), 2600; https://doi.org/10.3390/foods14152600 - 24 Jul 2025
Viewed by 401
Abstract
Background/Objectives: The liver, the body’s primary detoxifying organ, is often affected by various inflammatory diseases, including hepatitis, cirrhosis, and non-alcoholic fatty liver disease (NAFLD), many of which can be exacerbated by secondary infections such as spontaneous bacterial peritonitis, bacteremia, and sepsis—particularly in patients [...] Read more.
Background/Objectives: The liver, the body’s primary detoxifying organ, is often affected by various inflammatory diseases, including hepatitis, cirrhosis, and non-alcoholic fatty liver disease (NAFLD), many of which can be exacerbated by secondary infections such as spontaneous bacterial peritonitis, bacteremia, and sepsis—particularly in patients with advanced liver dysfunction. The global rise in these conditions underscores the need for effective interventions. Natural products have attracted attention for their potential to support liver health, particularly through synergistic combinations of plant extracts. Epavin, a dietary supplement from Erbenobili S.r.l., formulated with plant extracts like Taraxacum officinale (L.), Silybum marianum (L.) Gaertn., and Cynara scolymus (L.), known for their liver-supporting properties, has been proposed as adjuvant for liver functions. The aim of this work was to evaluate of Epavin’s antioxidant, anti-inflammatory, and protective effects against heavy metal-induced toxicity. In addition, the antibacterial effect of Epavin against a panel of bacterial strains responsible for infections associated with liver injuries has been evaluated. Methods: The protection against oxidative stress induced by H2O2 was evaluated in HepG2 and BALB/3T3 cells using the dichlorofluorescein diacetate (DCFH-DA) assay. Its anti-inflammatory activity was investigated by measuring the reduction in nitric oxide (NO) production in LPS-stimulated RAW 264.7 macrophages using the Griess assay. Additionally, the cytoprotecting of Epavin against heavy metal-induced toxicity and oxidative stress were evaluated in HepG2 cells using the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide] (MTT) and DCFH-DA assays. The antibacterial activity of Epavin was assessed by determining the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) against Gram-positive (Enterococcus faecalis ATCC 29212, and BS, Staphylococcus aureus 25923, 29213, 43300, and BS) and Gram-negative (Escherichia coli 25922, and BS, Klebsiella pneumoniae 13883, 70063, and BS) bacterial strains using the microdilution method in broth, following the Clinical and Laboratory Standards Institute’s (CLSI) guidelines. Results: Epavin effectively reduced oxidative stress in HepG2 and BALB/3T3 cells and decreased NO production in LPS-stimulated RAW 264.7 macrophages. Moreover, Epavin demonstrated a protective effect against heavy metal-induced toxicity and oxidative damage in HepG2 cells. Finally, it exhibited significant antibacterial activity against both Gram-positive and Gram-negative bacterial strains, with MIC values ranging from 1.5 to 6.0 mg/mL. Conclusions: The interesting results obtained suggest that Epavin may serve as a valuable natural adjuvant for liver health by enhancing detoxification processes, reducing inflammation, and exerting antibacterial effects that could be beneficial in the context of liver-associated infections. Full article
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20 pages, 2015 KiB  
Article
Origanum majorana Extracts: A Preliminary Comparative Study on Phytochemical Profiles and Bioactive Properties of Valuable Fraction and By-Product
by Simone Bianchi, Rosaria Acquaviva, Claudia Di Giacomo, Laura Siracusa, Leeyah Issop-Merlen, Roberto Motterlini, Roberta Foresti, Donata Condorelli and Giuseppe Antonio Malfa
Plants 2025, 14(15), 2264; https://doi.org/10.3390/plants14152264 - 23 Jul 2025
Viewed by 310
Abstract
Origanum majorana L. (O. majorana) (Lamiaceae) is an aromatic Mediterranean plant widely used in food, cosmetics, and traditional medicine due to its aroma and rich content of bioactive compounds. While its leaves and flowers are commonly utilized, lignified stems are often [...] Read more.
Origanum majorana L. (O. majorana) (Lamiaceae) is an aromatic Mediterranean plant widely used in food, cosmetics, and traditional medicine due to its aroma and rich content of bioactive compounds. While its leaves and flowers are commonly utilized, lignified stems are often discarded. This study compared hydroalcoholic extracts from the leaves and flowers (valuable fraction, VF) and stems (by-product, BP). Phytochemical analysis revealed qualitatively similar profiles, identifying 20 phenolic compounds, with Rosmarinic acid and Salvianolic acid B as the most and second most abundant, respectively. Antioxidant activity was evaluated in vitro using DPPH (IC50 [µg/mL]: VF 30.11 ± 3.46; BP 31.72 ± 1.46), H2O2 (IC50 [µg/mL]: VF 103.09 ± 4.97; BP 119.55 ± 10.58), and O2•− (IC50 [µg/mL]: VF 0.71 ± 0.062; BP 0.79 ± 0.070). Both extracts (20 µg/mL) fully restored oxidative balance in hemin-stressed AC16 cardiomyocytes, without altering the expression of catalase, heme-oxygenase 1, superoxide dismutase 2, or ferritin. Anti-inflammatory activity in LPS-stimulated RAW 264.7 macrophages showed that VF (IC50 400 µg/mL) reduced NO release to control levels, while BP achieved a ~60% reduction. Cytotoxicity was assessed on cancer cell lines: CaCo-2 (IC50 [µg/mL]: VF 154.1 ± 6.22; BP 305.2 ± 15.94), MCF-7 (IC50 [µg/mL]: VF 624.6 ± 10.27; BP 917.9 ± 9.87), and A549 (IC50 [µg/mL]: VF 720.8 ± 13.66; BP 920.2 ± 16.79), with no cytotoxicity on normal fibroblasts HFF-1 (IC50 > 1000 µg/mL for both extracts). Finally, both extracts slightly inhibited only CYP1A2 (IC50 [µg/mL]: VF 497.45 ± 9.64; BP 719.72 ± 11.37) and CYP2D6 (IC50 [µg/mL]: VF 637.15 ± 14.78, BP 588.70 ± 11.01). These results support the potential reuse of O. majorana stems as a sustainable source of bioactive compounds for nutraceutical and health-related applications. Full article
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29 pages, 15117 KiB  
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 436
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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27 pages, 21524 KiB  
Article
Synergistic Combinations of Native Australian Plants For Skin Inflammation and Wound Healing
by Rotina Kapini, Dennis Chang, Gerald Münch, Lisa Carroll and Xian Zhou
Biomedicines 2025, 13(7), 1754; https://doi.org/10.3390/biomedicines13071754 - 17 Jul 2025
Viewed by 468
Abstract
Background: Inflammation and oxidative stress are key mechanisms in underlying skin conditions like psoriasis and eczema. While many plants, including Australian native plants, are proposed to target these pathways due to their phytochemical content, studies on whole extracts and their synergistic effects remain [...] Read more.
Background: Inflammation and oxidative stress are key mechanisms in underlying skin conditions like psoriasis and eczema. While many plants, including Australian native plants, are proposed to target these pathways due to their phytochemical content, studies on whole extracts and their synergistic effects remain limited. Objectives: This study aimed to investigate individual and combined effects of whole plant extracts on skin protection and healing, focusing on their anti-inflammatory and antioxidant properties. Methods: The antioxidant potential of the individual and combined plant extracts were investigated on 2,2-diphenyl-1-picrylhydrazyl (DPPH) and reactive oxygen species (ROS) assay followed by luciferase assay in MCF-7 AREc32 cells for nuclear factor erythroid 2-related factor 2 (Nrf2) activation. The anti-inflammatory activities were investigated on lipopolysaccharide (LPS)-induced RAW 264.7 murine macrophages for the inhibition of nitric oxide (NO), tumour necrosis factor (TNF)-α, and interleukin (IL)-6. Synergistic interaction was determined by the combination index model (CI < 1). Combination(s) showing synergistic and optimal activity were further investigated on LPS-induced human dermal fibroblasts (HDF) cells for IL-6 inhibition and wound healing activity. Results: Three of the tested Australian native plant extracts demonstrated prominent antioxidant and anti-inflammatory activities including bitter orange, mountain pepper berry and native river mint. In particular, their three-way combination (1:1:1, w/w) showed prominent synergistic (CI < 1) in reducing NO and IL-6, along with enhanced Nrf2 activation. In LPS-inflamed HDF cells, the combination maintained synergistic inhibition of IL-6 levels and promoted wound healing response. Conclusions: These findings highlight the therapeutic potential of Australian native plant as a whole extract for skin protection and repair attributed to antioxidant and anti-inflammatory activities. The observed synergistic anti-inflammatory and antioxidant effects support their use in the development of new cosmetic formulations for skin. Full article
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16 pages, 3252 KiB  
Article
Chlorella pyrenoidosa Polysaccharide CPP-3a Promotes M1 Polarization of Macrophages via TLR4/2-MyD88-NF-κB/p38 MAPK Signaling Pathways
by Yihua Pi, Qingxia Yuan, Shaoting Qin, Chundie Lan, Qingdong Nong, Chenxia Yun, Haibo Tang, Jing Leng, Jian Xiao, Longyan Zhao and Lifeng Zhang
Mar. Drugs 2025, 23(7), 290; https://doi.org/10.3390/md23070290 - 16 Jul 2025
Viewed by 402
Abstract
The immunomodulatory polysaccharide CPP-3a, purified from Chlorella pyrenoidosa, was investigated for its effects on RAW264.7 macrophages and underlying mechanisms, revealing that CPP-3a significantly enhanced phagocytic capacity and nitric oxide production while upregulating pro-inflammatory cytokines TNF-α and IL-6 and elevating the co-stimulatory molecule [...] Read more.
The immunomodulatory polysaccharide CPP-3a, purified from Chlorella pyrenoidosa, was investigated for its effects on RAW264.7 macrophages and underlying mechanisms, revealing that CPP-3a significantly enhanced phagocytic capacity and nitric oxide production while upregulating pro-inflammatory cytokines TNF-α and IL-6 and elevating the co-stimulatory molecule CD86, collectively driving robust M1 polarization. Mechanistically, TLR4-, TLR2-specific inhibitors, and TLR4-knockout cells confirmed TLR4 as the primary receptor for CPP-3a, with TLR2 playing a secondary role in cytokine modulation. CPP-3a activated NF-κB and p38 MAPK signaling pathways via the MyD88-dependent pathway, evidenced by phosphorylation of NF-κB/p65 with its nuclear translocation and increased phosphorylation of p38 MAPK, with these signaling activations further validated by specific pathway inhibitors that abolished M1 polarization phenotypes. Collectively, CPP-3a emerges as a potent TLR4-targeted immunomodulator with adjuvant potential for inflammatory and infectious diseases. Full article
(This article belongs to the Special Issue Marine Natural Products as Regulators in Cell Signaling Pathway)
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15 pages, 1389 KiB  
Article
Suppression of LPS-Induced Inflammation by Phragmites communis Young Leaf Extract via Multi-Target Inhibition of IκB, AP-1, and STAT1/3 Pathways in RAW 264.7 Cells
by Kyung-Yun Kang and Kyung-Wuk Park
Plants 2025, 14(14), 2178; https://doi.org/10.3390/plants14142178 - 14 Jul 2025
Viewed by 329
Abstract
Young leaves of reed (Phragmites communis) have been reported to exhibit antioxidant effects; however, their anti-inflammatory properties have not yet been investigated. In this study, we evaluated the effects of young reed leaf extract (PCE) on LPS-induced inflammation in RAW 264.7 [...] Read more.
Young leaves of reed (Phragmites communis) have been reported to exhibit antioxidant effects; however, their anti-inflammatory properties have not yet been investigated. In this study, we evaluated the effects of young reed leaf extract (PCE) on LPS-induced inflammation in RAW 264.7 cells and elucidated the underlying molecular mechanisms. Our results demonstrate that PCE significantly inhibited the production of nitric oxide (NO) by approximately 45% at 100 μg/mL (p < 0.01) and pro-inflammatory cytokines such as IL-6, TNF-α, and GM-CSF by 40–60% (p < 0.01) in LPS-stimulated RAW 264.7 macrophages, without cytotoxicity up to 100 μg/mL. PCE also downregulated the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and upregulated heme oxygenase-1 (HO-1) expression by approximately 2-fold at 100 μg/mL (p < 0.05). Mechanistically, these effects were associated with the inhibition of IκBα phosphorylation/degradation, IKKα/β phosphorylation, and AP-1 activation via the suppression of JNK and ERK signaling pathways, as well as the inhibition of STAT1/3 phosphorylation. Collectively, our findings suggest that PCE exerts anti-inflammatory effects by modulating the IκB, AP-1, and STAT1/3 signaling pathways, thereby suppressing inflammatory mediator production and enhancing antioxidant defense mechanisms in LPS-treated macrophages. Full article
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16 pages, 4613 KiB  
Article
Perfluorononanoic Acid (PFNA) Exacerbates Atopic Dermatitis by Inducing Inflammation in Mice
by Jiali Xiao, Junchao Wang, Nuo Xu, Xulong Huang, Farid Khalilov, Xianfeng Huang, Xiangyong Zheng, Xiashun Xu, Shisheng Lin, Wengang Zhao and Elchin Khalilov
Toxics 2025, 13(7), 585; https://doi.org/10.3390/toxics13070585 - 13 Jul 2025
Viewed by 475
Abstract
Perfluorononanoic acid (PFNA) is a ubiquitous persistent environmental pollutant, and several studies have found significant links between atopic dermatitis (AD) and prenatal exposure to PFNA. However, the relationship between PFNA and AD remains unclear. In this study, 2,4-dinitrochlorobenzene (DNCB)-treated female BALB/c mice were [...] Read more.
Perfluorononanoic acid (PFNA) is a ubiquitous persistent environmental pollutant, and several studies have found significant links between atopic dermatitis (AD) and prenatal exposure to PFNA. However, the relationship between PFNA and AD remains unclear. In this study, 2,4-dinitrochlorobenzene (DNCB)-treated female BALB/c mice were used as AD models to investigate the effects of PFNA and its potential mechanisms. These mice were topically applied with 5 mg/kg PFNA per day for 15 days. The results demonstrated that PFNA significantly increased AD lesion severity and clinical symptoms, including dermatitis score, ear thickness, and epidermal thickness. In addition, PFNA also increased the serum IgE level, splenic atrophy, and upregulated the expression of TNF-α, IL-6, and IL-, genes that are associated with skin inflammatory factors. In addition, Western blot results showed that PFNA treatment upregulated the expression of p-JNK protein. Additionally, cellular experiments indicated that RAW264.7 macrophages and mouse brain microvascular endothelial (bEnd.3) cells treated with PFNA at concentrations of 0.01–100 μM for 72 h showed no changes in cell viability. However, 100 μM PFNA upregulated the mRNA expression levels of the pro-inflammatory cytokines IL-1β and IL-6, as well as the protein expression of p-JNK, in RAW264.7 cells induced with 1 mg/mL LPS for 2 h. Similarly, PFNA increased TNF-α and IL-6 mRNA expression and p-JNK protein expression in bEnd.3 cells stimulated with 20 ng/mL TNF-α for 0.5 h. Based on these findings, we can conclude that PFNA may aggravate atopic dermatitis by promoting inflammation. Full article
(This article belongs to the Section Emerging Contaminants)
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23 pages, 2078 KiB  
Article
Antioxidant and Anti-Inflammatory Activities of Thai Traditional Hand and Foot Soaking Formulary and Its Bioactive Compounds
by Jaenjira Angsusing, Weerasak Samee, Supachoke Mangmool, Usma Dortae, Pranot Keawthip, Surakameth Mahasirimongkol, Somsak Kreechai, Kulthanit Wanaratna, Chuda Chittasupho and Nopparut Toolmal
Pharmaceutics 2025, 17(7), 907; https://doi.org/10.3390/pharmaceutics17070907 - 13 Jul 2025
Viewed by 527
Abstract
Background/Objectives: This study aimed to investigate the antioxidant and anti-inflammatory properties of a Hand and Foot Soaking Formulary composed of ten medicinal plants, with curcumin as a major bioactive marker, to provide scientific validation for its traditional use. Methods: The formulation was [...] Read more.
Background/Objectives: This study aimed to investigate the antioxidant and anti-inflammatory properties of a Hand and Foot Soaking Formulary composed of ten medicinal plants, with curcumin as a major bioactive marker, to provide scientific validation for its traditional use. Methods: The formulation was evaluated for total phenolic and flavonoid contents, with curcumin quantified using HPLC. Antioxidant activity was assessed using DPPH, ABTS, and FRAP assays. Cytotoxicity was evaluated in RAW264.7 cells using the MTT assay. Anti-inflammatory activity was determined by measuring nitric oxide (NO), PGE2, TNF-α, IL-1β, and IL-6 levels in LPS-stimulated RAW264.7 macrophages using ELISA. Results: The Hand and Foot Soaking Formulary exhibited promising antioxidant and anti-inflammatory properties, consistent with its traditional use. Phytochemical analysis confirmed the presence of bioactive compounds, with measurable levels of total phenolics, flavonoids, and significant curcumin content. Antioxidant activity was demonstrated through free radical scavenging and ferric-reducing assays, while cytotoxicity testing in RAW264.7 macrophages indicated low toxicity (IC50 = 48.61 ± 3.80 µg/mL). The formulary significantly reduced LPS-induced nitric oxide, PGE2, TNF-α, IL-1β, and IL-6 production. These effects were comparable to turmeric extract and curcumin, though curcumin displayed higher potency. Conclusions: The Hand and Foot Soaking Formulary demonstrates antioxidant and anti-inflammatory properties in vitro, supporting its traditional use. Its polyherbal composition may offer synergistic effects and holds promise as a safe, natural topical remedy. Full article
(This article belongs to the Special Issue Natural Compounds in Drug Delivery Systems)
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17 pages, 2075 KiB  
Article
Chemical Profiles and Nitric Oxide Inhibitory Activities of the Copal Resin and Its Volatile Fraction of Bursera bipinnata
by Silvia Marquina, Mayra Antunez-Mojica, Judith González-Christen, Antonio Romero-Estrada, Fidel Ocampo-Bautista, Ninfa Yaret Nolasco-Quintana, Araceli Guerrero-Alonso and Laura Alvarez
Forests 2025, 16(7), 1144; https://doi.org/10.3390/f16071144 - 11 Jul 2025
Viewed by 387
Abstract
Bursera bipinnata (DC.) Engl. (B. bipinnata), commonly known as “copal chino,” is a widely distributed Mexican tree found in transitional zones between pine-oak and deciduous forests. It is valued for its high-quality copal resin, traditionally used in ceremonies and offerings. Additionally, B. bipinnata [...] Read more.
Bursera bipinnata (DC.) Engl. (B. bipinnata), commonly known as “copal chino,” is a widely distributed Mexican tree found in transitional zones between pine-oak and deciduous forests. It is valued for its high-quality copal resin, traditionally used in ceremonies and offerings. Additionally, B. bipinnata is recognized for its significant value in traditional medicine, particularly in treating ailments associated with inflammation. In this work, the inhibition of nitric oxide (NO) production of the volatile fraction and resin of B. bipinnata in LPS-stimulated RAW 264.7 macrophage cells were demonstrated. In contrast, the volatile fraction exhibited 37.43 ± 7.13% inhibition at a concentration of 40 µg/mL. Chromatographic analyses of the total resin enabled the chemical characterization of eleven pentacyclic triterpenes belonging to the ursane, oleanane, and lupane series, as well as eight monoterpenes. Notably, the structures of compounds 15, 17, and 2935 are reported for the first time from the resin of Bursera bipinnata. The anti-inflammatory activity observed for B. bipinnata resin in this study may be attributed to its high content of the triterpenes α-amyrin (15, 29.7%) and 3-epilupeol (17, 38.1%), both known for their anti-inflammatory properties. These findings support the traditional use of this copal resin. Full article
(This article belongs to the Special Issue Medicinal and Edible Uses of Non-Timber Forest Resources)
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29 pages, 15583 KiB  
Article
Neuroinflammation Based Neurodegenerative In Vitro Model of SH-SY5Y Cells—Differential Effects on Oxidative Stress and Insulin Resistance Relevant to Alzheimer’s Pathology
by Csenge Böröczky, Alexandra Paszternák, Rudolf Laufer, Katinka Tarnóczi, Noémi Sikur, Fruzsina Bagaméry, Éva Szökő, Kamilla Varga and Tamás Tábi
Int. J. Mol. Sci. 2025, 26(14), 6581; https://doi.org/10.3390/ijms26146581 - 9 Jul 2025
Viewed by 519
Abstract
Neuroinflammation is a key process in Alzheimer’s disease (AD). We aimed to examine the development and evaluation of a comprehensive in vitro model that captures the complex interplay between neurons and immune cell types. Retinoic acid-differentiated SH-SY5Y neuroblastoma cells exposed to LPS-conditioned media [...] Read more.
Neuroinflammation is a key process in Alzheimer’s disease (AD). We aimed to examine the development and evaluation of a comprehensive in vitro model that captures the complex interplay between neurons and immune cell types. Retinoic acid-differentiated SH-SY5Y neuroblastoma cells exposed to LPS-conditioned media (CM) from RAW264.7 macrophages, BV2 microglia, and HL60 promyelocytic cells differentiated into neutrophil- or monocyte-like phenotypes were analyzed. The effects of CM containing inflammatory factors on neuronal viability and function were systematically evaluated. Neuronal oxidative stress, mitochondrial function, autophagy and protein aggregates were analyzed. The involvement of insulin resistance was studied by assaying glucose uptake and determining its IC50 values for cell viability improvement and GSK3β phosphorylation. After short-term exposure (3 h), most inflammatory CMs induced peroxide production in neurons, with the strongest effect observed in media from DMSO- or RA-differentiated HL60 cells. Mitochondrial membrane potential was markedly reduced by LPS-stimulated BV2 and HL60-derived CMs. Prolonged exposure (72 h) revealed partial normalization of oxidative stress and mitochondrial membrane potential. Glucose uptake was significantly impaired in cells treated with LPS-activated RAW264.7, BV2, and DMSO-differentiated HL60 cell media, while insulin partially rescued this effect, except for the CM of BV2 cells. Notably, insulin IC50 increased dramatically under LPS-treated BV2 cells induced inflammation (35 vs. 198 pM), confirming the development of insulin resistance. Immune cell-specific inflammation causes distinct effects on neuronal oxidative stress, mitochondrial function, protein aggregation, insulin signaling and viability. LPS-activated BV2-derived CM best recapitulates AD-related pathology, offering a relevant in vitro model for further studies. Full article
(This article belongs to the Section Molecular Neurobiology)
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23 pages, 3707 KiB  
Article
Structural and Functional Profiling of Water-Extracted Polypeptides from Periplaneta americana: A Multifunctional Cosmetic Bioactive Agent with Antioxidative and Anti-Inflammatory Properties
by Xinyu Sun, Zhengyang Zhang, Jingyao Qu, Deyun Yao, Zeyuan Sun, Jingyi Zhou, Jiayuan Xie, Mingyang Zhou, Xiaodeng Yang and Ling Wang
Molecules 2025, 30(14), 2901; https://doi.org/10.3390/molecules30142901 - 9 Jul 2025
Viewed by 459
Abstract
Low-molecular-weight polypeptides (<3 kDa) were prepared from Periplaneta americana via enzymatic hydrolysis and ultrafiltration, yielding 3.53 ± 0.01 mg/g of peptide-rich extract. The extract was primarily composed of peptides, proteins, polysaccharides, phenolics, and flavonoids. HPLC-MS analysis identified 1402 peptide sequences, 80.51% of which [...] Read more.
Low-molecular-weight polypeptides (<3 kDa) were prepared from Periplaneta americana via enzymatic hydrolysis and ultrafiltration, yielding 3.53 ± 0.01 mg/g of peptide-rich extract. The extract was primarily composed of peptides, proteins, polysaccharides, phenolics, and flavonoids. HPLC-MS analysis identified 1402 peptide sequences, 80.51% of which were below 1000 Da, predominantly consisting of tri-, tetra-, and octapeptides. Monosaccharide profiling detected D-(+)-galactose, and quantitative assays determined the contents of total phenolics (12.28 mg/g), flavonoids (15.50 mg/g), proteins (85.84 mg/g), and total sugars (17.62 mg/g). The biological activities of the extract were systematically evaluated. The peptide fraction inhibited hyaluronidase activity by 58% at 5 mg/mL, suggesting protection of extracellular matrix integrity. In HaCaT keratinocytes, it promoted cell proliferation by 62.6%, accelerated scratch wound closure by 54%, upregulated Wnt-10b and β-catenin expression, and reduced intracellular ROS levels under oxidative stress. In LPS-stimulated RAW 264.7 macrophages, the extract decreased TNF-α, IL-6, and IL-1β production by 30%, 25%, and 28%, respectively, reduced MDA levels by 35.2%, and enhanced CAT and SOD activities by 12.3% and 60.3%. In vivo, complete closure of full-thickness skin wounds in mice was achieved by day 14. Safety evaluations using the chick chorioallantoic membrane assay and human patch tests confirmed the extract to be non-irritating and non-toxic. These findings highlight Periplaneta americana extract as a promising multifunctional bioactive ingredient for cosmetic and dermatological applications. Further studies on its active components, mechanisms of action, and clinical efficacy are warranted to support its development in skin health and aesthetic medicine. Full article
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