Search Results (46)

Acrolein, a highly reactive environmental toxicant widely present in urban air and tobacco smoke, has been implicated in the development of multiple malignancies. In oral tissues, chronic acrolein exposure induces oxidative stress, inflammation, and genetic mutations, all of which are closely linked to the development of oral squamous cell carcinoma (OSCC). Although accumulating evidence indicates a strong association between acrolein exposure and OSCC, its prognostic significance remains poorly understood. In this study, we analyzed transcriptome data to identify differentially expressed genes (DEGs) between tumor and adjacent normal tissues, and screened acrolein-related candidates by intersecting DEGs with previously identified acrolein-associated gene sets. Functional alterations of these genes were assessed using Gene Set Variation Analysis (GSVA), and a protein–protein interaction (PPI) network was constructed to identify key regulatory genes. A prognostic model was developed using Support Vector Machine–Recursive Feature Elimination (SVM-RFE) combined with LASSO-Cox regression and validated in an independent external cohort. Among the acrolein-related DEGs, four key genes (PLK1, AURKA, CTLA4, and PPARG) were ultimately selected for model construction. Kaplan–Meier analysis showed significantly worse overall survival in the high-risk group (p < 0.0001). Receiver operating characteristic (ROC) curve analysis further confirmed the strong predictive performance of the model, with area under the curve (AUC) values of 0.72 at 1 year, 0.72 at 3 years, and 0.75 at 5 years. Furthermore, the high risk score was significantly correlated with a ‘cold’ immune microenviroment, suggesting that acrolein-related genes may modulate the tumor immune microenvironment. Collectively, these findings highlight the role of acrolein in OSCC progression, suggesting the importance of reducing acrolein exposure for cancer prevention and public health, and call for increased attention to the relationship between environmental toxicants and disease initiation, providing a scientific basis for public health interventions and cancer prevention strategies. Full article

Opophytum forskahlii has a well-established ethnopharmacological significance. This study aimed to assess the skin anti-aging and hair growth-promoting activities of O. forskahlii seed oil (OFSO) and the underlying mechanism. GC-MS profiling revealed high levels of unsaturated fatty acids, linoleic acid (55.46%), and oleic acid (38.54%). The skin anti-aging activity of OFSO (3.125–100 µg/mL) was evaluated in normal human dermal fibroblasts (NHDFs) using MTT and enzyme inhibition assays. OFSO was non-cytotoxic and enhanced fibroblast proliferation in a dose-dependent manner, reaching 145.5% of control at 100 µg/mL (p < 0.05). OFSO significantly (p < 0.05) inhibited collagenase (48%), hyaluronidase (53%), elastase (57%), and tyrosinase (55%). The oil showed anti-inflammatory activity by inhibiting COX-1 and COX-2 (0.01–100 µg/mL) with IC₅₀ = 0.125 and 0.014 µg/mL, respectively. The hair growth promoting efficacy was assessed using adult male Wistar rats, randomly divided into control, OFSO-treated, and 2% minoxidil-treated groups (5 rats/group). Hair growth was assessed through visual scoring over 14 days of topical application and confirmed by histological examination and hair follicle counting. On day 14, the OFSO-treated group displayed almost complete hair coverage (score about 5.0), exceeding minoxidil (about 4.0), and significantly increased hair follicle number (14.0 ± 1 vs. 9.2 ± 0.8, p < 0.05). Histology confirmed that OFSO promoted hair follicle growth, differentiation, and transition from the telogen to the anagen phase. Network pharmacology analysis, integrating targets predicted via SwissTargetPrediction and disease-associated genes from GeneCards, identified PPARG, ESR1, and IL6 as key hub genes underlying OFSO’s effects. PPARG enhances antioxidant defenses, anti-inflammatory responses, and sebaceous gland function; ESR1 supports collagen production, skin elasticity, and follicle vascularization; and IL6 modulates inflammation and triggers the anagen phase of hair growth. Functional enrichment revealed modulation of PPAR, estrogen, prolactin, and arachidonic acid metabolism pathways, suggesting that OFSO may regulate lipid metabolism, inflammation, hormonal signaling, and tissue regeneration. OFSO demonstrated promising anti-aging and hair growth activities, supporting further development and testing of cosmetic formulations. Full article

Background: Non-alcoholic steatohepatitis (NASH) lacks approved pharmacotherapies despite affecting approximately 25% of the global population. Agrimonia pilosa, a traditional herb with anti-inflammatory and antioxidant properties, remains unexplored for NASH treatment. Objective: This study investigated the hepatoprotective effects and mechanisms of Agrimonia pilosa extract (APE) in NASH models. Methods: HepG2 cells were treated with free fatty acids (0.125 mM) and APE (+12.5–50 μg/mL). C57BL/6J mice received a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) for 12 weeks with APE (25–100 mg/kg/day), silymarin (100 mg/kg/day), or luteolin (20 mg/kg/day). Lipid accumulation, liver enzymes, histopathology, and molecular markers were assessed. Results: APE dose-dependently reduced lipid accumulation in FFA-treated cells, suppressed lipogenic factors (SREBF1, CEBPA, and PPARG), and upregulated fatty acid oxidation enzymes (CPT1A and PPARA) via AMPK/SIRT1 activation. In NASH mice, APE (100 mg/kg) significantly decreased serum ALT (160.0 ± 49.1 vs. 311.2 ± 66.7 U/L) and AST (96.0 ± 18.7 vs. 219.0 ± 55.7 U/L, p < 0.001), reduced hepatic macrophage infiltration by 68%, and substantially attenuated inflammatory markers (Ccl2, Tnf, and IL6), oxidative stress indicators (NRF2, HMOX1, and CYBB), and fibrogenic markers (ACTA2, COL1A1, and TGFB1) by 83–85% (p < 0.001). Collagen deposition decreased from 5.63 ± 0.39% to 1.54 ± 0.03% (p < 0.001). Conclusions: APE exerts potent hepatoprotective effects through multi-targeted modulation of lipid metabolism, inflammation, oxidative stress, and fibrosis via AMPK/SIRT1 pathway activation, supporting its potential as a natural therapeutic intervention for NASH. Full article

Biebersteinia heterostemon is a traditional Tibetan medicine known for its antioxidant, hypoglycemic, and anti-atherosclerotic properties. However, its therapeutic effects and mechanisms in the treatment of hyperlipidemia remain unclear. In this study, the ethyl acetate extract of B. heterostemon (BHEE) was first identified as the most effective lipid-lowering fraction through its inhibitory activity on pancreatic lipase and cholesterol esterase. Chemical characterization of BHEE by UHPLC-MS/MS revealed 108 compounds. Network pharmacology and molecular docking analyses were then employed to predict key active components and signaling pathways involved in BHEE’s lipid-lowering effects. A total of 50 active components and 623 targets were selected from the PubChem, SwissADME, and Swiss Target Prediction databases. These targets were intersected with 1606 hyperlipidemia-related targets from GeneCards, OMIM, and DrugBank, resulting in 144 common targets. The “drug-active component-intersecting target-pathway-HLP” and protein–protein interaction (PPI) networks suggested key active components such as 6-methoxytricin, vulgarin, flazin, ganhuangenin, and eupatorin, and core targets including TNF, IL6, AKT1, PPARG, and EGFR. GO and KEGG pathway enrichment analysis highlighted potential signaling pathways, such as AGE-RAGE, PPAR, insulin resistance, TNF, and lipid and atherosclerosis pathways. Molecular docking further predicted the strong binding affinity between key active components and core targets. At the cellular level, BHEE dose-dependently reduced lipid accumulation in FFA-induced HepG2 cells and improved oxidative stress (CAT, GSH, SOD, MDA) and inflammation (TNF-α, IL-6) markers. In conclusion, BHEE may exert its anti-hyperlipidemic effects through modulation of key targets like TNF, IL6, AKT1, PPARG, and EGFR. These findings suggest a multi-target mechanism, though further experimental validation is necessary to confirm these effects. This study provides valuable insights into the potential application of B. heterostemon as a natural therapeutic agent for hyperlipidemia. Full article

Atopic dermatitis (AD) is a multifactorial skin disorder characterized by immune and barrier dysfunction. The gut–skin axis is a bidirectional pathway through which gut and skin influence each other via microbial metabolites. Bioactive metabolites produced by microbial transformation of phytochemicals show potential for AD prevention. This study developed a computational systems biology pipeline that prioritized gut-derived metabolites from Philippine medicinal plants by integrating metabolite prediction, pharmacokinetics, network analysis, and molecular simulations. From 2231 predicted metabolites, 31 satisfied pharmacological criteria and were mapped to 199 AD-associated targets, with ALB, CASP3, and PPARG identified as hub genes. Two metabolites, THPOC and PM38, exhibited complementary target affinities and strong binding stability. THPOC stabilized ALB and CASP3, supporting barrier integrity and apoptosis regulation, while PM38 strongly engaged PPARG, modulating lipid metabolism and anti-inflammatory transcription. They exhibited comparable or superior docking scores, stable MD interactions, and favorable binding free energies, compared to abrocitinib, an approved AD treatment. DFT analysis confirmed electronic stability and donor–acceptor properties linked to target selectivity. These findings highlight THPOC and PM38 as promising immunometabolic modulators acting on key AD-related pathways. Collectively, this study introduces a reproducible systems-based computational discovery framework, offering a novel preventive strategy for AD. Full article

2,4-Dichlorophenoxyacetic acid (2,4-D) is a widely used herbicide, yet its potential to induce hepatorenal injury via oxidative stress and apoptosis raises significant health concerns. Lycium barbarum polysaccharides (LBP) possess recognized antioxidant and anti-apoptotic properties, but their protective mechanisms against 2,4-D toxicity, particularly through a multi-target network, remain inadequately explored. This study aimed to systematically investigate the mechanisms of 2,4-D-induced hepatorenal injury and the protective efficacy of LBP by integrating network toxicology, molecular docking, and experimental validation. An integrated approach was employed. Core targets and pathways were identified via network toxicology. Molecular docking predicted interactions between 2,4-D and these targets. In vivo validation was conducted on Sprague-Dawley rats treated with 2,4-D (75 mg/kg) and/or LBP (50 mg/kg) for 28 days, assessing histopathology, serum oxidative stress markers superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA) and cellular apoptosis (TUNEL staining). Network analysis identified PPARG, NFKB1, PPARA, NFE2L2, and SERPINE1 as core targets, with molecular docking confirming strong binding affinities (binding energies: −5.1 to −6.3 kcal·mol⁻¹) and KEGG enrichment implicating cAMP, Ca²⁺, and PPAR signaling pathways. Experimentally, 2,4-D exposure induced significant histopathological damage, suppressed SOD/GSH-Px activities (p < 0.001), elevated MDA levels (p < 0.001), and markedly increased renal apoptosis (p < 0.01). Crucially, LBP intervention substantially mitigated these alterations, ameliorating tissue injury, restoring antioxidant defenses, increasing SOD/GSH-Px (p < 0.01), reducing MDA (p < 0.001) and significantly decreasing renal apoptosis (p < 0.05). This study elucidates a multi-target mechanism for 2,4-D-induced hepatorenal injury centered on oxidative stress–apoptosis dysregulation and demonstrates that LBP confers significant protection likely via modulation of this network. These findings underscore the potential of LBP as a natural protective agent against pesticide-induced organ damage and highlight the utility of integrated network approaches in toxicological research. Full article

Athletic performance results from complex interactions between genetic and environmental factors. This review compiles and synthesizes available literature on polymorphic genes associated with endurance, power, and strength performance, as well as their links to injury susceptibility and chronic metabolic diseases. Endurance performance is modulated by ACE, PPARGC1A, HFE, UCP2, UCP3, CDKN1A, and PPARA, regulating mitochondrial biogenesis, oxygen utilization, and muscle fiber composition. Power performance involves ACTN3, MCT1, IGF1, AMPD1, AGT, and AGTR2, affecting anaerobic metabolism, lactate clearance, and fast-twitch fiber recruitment. Strength performance is influenced by AR, PPARG, ARK2N, MMS22L, LRPPRC, PHACTR1, and MTHFR, related to androgen signaling, muscle hypertrophy, and recovery. Injury-related genes (COL1A1, COL5A1, IL6, VEGFA, NOG) and metabolic risk genes (FTO, PPARG, ADRB3) further highlight the clinical relevance of genomics. Collectively, these insights support the application of genetic information to personalize training, enhance performance, prevent injuries, and guide exercise interventions to mitigate metabolic disease risk. Full article

This study aims to investigate the effect and mechanism of resveratrol (RES) on lipopolysaccharide (LPS)-induced injury in goat granulosa cells (GCs). First, the appropriate time and concentration were screened for LPS (4 μg/mL, 12 h), RES (1 μM, 6 h), and GW9662 (an antagonist of PPARG, 1 μM, 12 h) through CCK8 and RT-qPCR. Then, cells were treated with LPS, RES, or/and GW9662, to examine steroidogenesis, inflammation, oxidative stress, and pyroptosis by RIA, RT-qPCR, WB, flow cytometry, and IF, respectively. Results showed that RES inhibited LPS-induced increases in MDA content, ROS production, gene expressions of IL-1β, NLRP3, Caspase1, and GSDMD, as well as protein levels of IL-1β, and GSDMD, accompanied by decreases in SOD activity, T-AOC and E2 content, gene expressions of SOD, CYP19A1, and HSD3B, and protein levels of SOD and HSD3B. Furthermore, RES inhibited LPS-induced decreases in PPARG, NRF2, and HO-1 gene expressions and protein levels. However, GW9662 could block all the alleviating effects of RES on LPS. In conclusion, RES regulates the effects of LPS on hormone secretion, inflammation, oxidative stress, and pyroptosis by modulating the PPARG/NRF2/HO-1 pathway, providing a new theoretical basis for improving goat reproduction. Full article

Background: Cardiovascular diseases, driven significantly by dyslipidemia, remain a leading global mortality risk. Emerging evidence indicates that Lactobacillus plantarum (L. plantarum), which is a probiotic commonly used in a variety of food products, may contribute to the regulation of blood lipids, although prior studies report inconsistent efficacy and lack mechanistic clarity. This study aimed to evaluate the effects of L. plantarum supplementation on blood lipid profiles and explore its potential mechanisms through a systematic review, meta-analysis, and network pharmacology. Methods: We performed a comprehensive literature search across PubMed, Cochrane Library, EMBASE, and other databases. Meta-analysis was performed using random-effects models to assess changes in total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). Network pharmacology was employed to predict molecular targets and pathways. Results: Twenty-six randomized controlled trials (RCTS) involving 2104 participants were included. L. plantarum supplementation significantly reduced TC (SMD: −0.233; 95% CI: −0.458, −0.008; p = 0.042), TG (SMD: −0.227; 95% CI: −0.432, −0.021; p = 0.030), and LDL-C (SMD: −0.251; 95% CI: −0.477, −0.025; p = 0.029), but not HDL-C. Subgroup analyses revealed greater efficacy with interventions lasting >8 weeks and single-strain formulations. Network pharmacology analysis highlighted IL-17/TNF signaling pathway, bile secretion, and other pathways as key mechanisms and targets such as PPARG and MMP9 as key targets. Conclusions: L. plantarum demonstrates significant lipid-lowering effects, particularly for TC, TG, and LDL-C, with sustained use and single-strain formulations yielding optimal outcomes. Mechanistically, it may modulate inflammation, oxidative stress, and lipid metabolism. These findings can support the development of a functional food and dietary supplement using L. plantarum to assist in the treatment of hyperlipidemia, though heterogeneity and strain-specific effects warrant further investigation. Full article

Periodontitis is a common inflammatory disease affecting the supporting structures of teeth. Epigallocatechin-3-gallate (EGCG), a polyphenol found in green tea, is known for its therapeutic properties in various diseases, including periodontitis. This study aims to identify the gene targets of EGCG and investigate its potential in modulating molecular pathways associated with periodontitis. The potential gene targets of EGCG were obtained from the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) and SwissTargetPrediction databases, while genes associated with periodontitis were sourced from GeneCards and Gene Expression Omnibus (GEO) datasets. By overlapping the two datasets, ten common target genes were identified. To explore their functional relevance, enrichment analyses such as Gene Ontology (GO) and REACTOME pathway mapping were conducted. Protein–protein interaction (PPI) networks were then generated, and further analyses involving molecular docking and molecular dynamics (MD) simulations were carried out to evaluate the binding affinity and structural stability of EGCG with the selected target proteins. Ten common genes (MMP2, MMP14, BCL2, STAT1, HIF1A, MMP9, MMP13, VEGFA, ESR1, and PPARG) were identified. PPI network and GO and pathway analyses identified the promising hub genes as ESR1, MMP2, MMP9, MMP13, and STAT1 and which highlighted roles in tissue development, extracellular matrix remodeling, and signaling pathways such as interleukin and matrix metalloproteinase activities. Molecular docking and MD simulations revealed strong binding interactions between EGCG and key proteins (ESR1, MMP2, MMP9, MMP13, and STAT1), with favorable binding energies and stable complexes. Among these, ESR1 and MMP13 exhibited the most favorable docking scores and stability in molecular dynamics simulations and MM–PBSA calculations. This study provides valuable insights into the molecular mechanisms of EGCG in periodontitis treatment. The findings suggest that ESR1 and MMP13 are the most promising targets for EGCG, supported by strong binding interactions and stable conformations in simulations. These results offer a foundation for further experimental studies and potential therapeutic applications of EGCG in managing periodontitis. Full article

Background: Sarcopenia is a syndrome associated with aging, characterized by a progressive decline in skeletal muscle mass and function. Its onset compromises the health and longevity of older adults by increasing susceptibility to falls, fractures, and various comorbid conditions, thereby diminishing quality of life and capacity for independent living. Accumulating evidence indicates that moderate-intensity aerobic exercise is an effective strategy for promoting overall health in older adults and exerts a beneficial effect that mitigates age-related sarcopenia. However, the underlying molecular mechanisms through which exercise confers these protective effects remain incompletely understood. Methods: In this study, we established a naturally aging mouse model to investigate the effects of a 16-week treadmill-based aerobic exercise regimen on skeletal muscle physiology. Results: Results showed that aerobic exercise mitigated age-related declines in muscle mass and function, enhanced markers associated with protein synthesis, reduced oxidative stress, and modulated the expression of genes and proteins implicated in mitochondrial quality control. Notably, a single session of aerobic exercise acutely elevated circulating levels of β-hydroxybutyrate (β-HB) and upregulated the expression of BDH1, HCAR2, and PPARG in the skeletal muscle, suggesting a possible role of β-HB–related signaling in exercise-induced muscle adaptations. However, although these findings support the beneficial effects of aerobic exercise on skeletal muscle aging, further investigation is warranted to elucidate the causal relationships and to characterize the chronic signaling mechanisms involved. Conclusions: This study offers preliminary insights into how aerobic exercise may modulate mitochondrial quality control and β-HB–associated signaling pathways during aging. Full article

Alzheimer’s disease (AD) is a complex neurodegenerative disorder characterized by multifactorial pathogenesis, including oxidative stress, cholinergic dysfunction, β-amyloid (Aβ) aggregation, and neuroinflammation. In this study, we investigated the neuroprotective potential of the Pheka capsule (PC) formula, a traditional Thai polyherbal medicine comprising Oroxylum indicum (OI), Zingiber officinale (ZO), and Boesenbergia rotunda (BR). Phytochemical analysis by HPLC confirmed the presence of key bioactive compounds including baicalein, baicalin, oroxylin A, 6-gingerol, 6-shogaol, pinocembrin, and pinostrobin. The PC formula exhibited strong antioxidant activity, highly selective butyrylcholinesterase (BChE) inhibition with a selectivity index (SI) of BChE > 20, suppression of Aβ aggregation, and protection against H₂O₂-induced neuronal damage in vitro. Network pharmacology analysis identified multiple AD-relevant targets and pathways, including APP, GSK3B, CASP3, GAPDH, PTGS2, and PPARG, implicating the PC formula in modulating oxidative stress, apoptosis, and inflammation. Notably, OI emerged as the primary contributor to the formula’s multitargeted actions. These findings support the therapeutic potential of the PC formula as a multitarget agent for AD, aligning with the growing interest in polypharmacological strategies for complex neurodegenerative diseases. Further in vivo and clinical studies are warranted to confirm its efficacy and safety. Full article

Background: Metabolic dysfunction-associated fatty liver disease (MASLD) is closely associated with immune dysregulation and macrophage-driven inflammation. The activation of PPARG plays a critical role in modulating macrophage polarization and lipid metabolism, suggesting its potential as a therapeutic target for MASLD. Methods: We used UPLC-Q/TOF-MS and network pharmacology to investigate the key components and targets of Swertia davidi Franch, focusing on Swertianin. In vitro experiments on macrophages were conducted to assess the modulation of M1 polarization, and a mouse model of MASLD was utilized to explore the therapeutic effects of Swertianin. Results: Swertianin activated PPARG, leading to significant inhibition of M1 macrophage polarization, a reduction in lipid accumulation, and decreased inflammatory marker levels both in vitro and in vivo. The treatment significantly improved liver pathology in mice, indicating its therapeutic potential for MASLD. Conclusions: Swertianin’s activation of PPARG provides a novel mechanism for treating MASLD, targeting both macrophage polarization and inflammation. Full article

Background/Objectives: Disruptions in adipose tissue dynamics contribute to obesity-related metabolic disorders, emphasizing the need for targeted therapies focusing on adipose tissue cells, including progenitor cells and adipocytes. Peroxisome proliferator-activated receptor gamma (PPARG) ligands are potent insulin sensitizers used in type 2 diabetes treatment. This study investigated the effects of rosiglitazone, a PPARG agonist, and betulinic acid, a PPARG antagonist, on adipogenesis and apoptosis in 3T3-L1 pre-adipocytes. Method: 3T3-L1 pre-adipocytes were treated with rosiglitazone or betulinic acid during adipogenic differentiation. Lipid droplet formation was used to evaluate adipogenesis. Cell growth and cell death were assessed using the resazurin-based cell viability assay, trypan blue exclusion assay, LDH assay, and Annexin V/PI staining. Quantitative PCR was conducted to examine the expression of genes associated with adipogenesis and apoptosis. Results: Betulinic acid reduced adipogenesis only when administered daily for eight days. Rosiglitazone did not alter the overall lipid quantity; however, it promoted a shift toward fewer but larger lipid droplets. Both compounds increased Adipoq and Cfd expression, and betulinic acid also elevated Fabp4. Rosiglitazone induced stronger cell aggregation. Despite increased cell death, overall viability was maintained. Apoptotic cell death was enhanced by both compounds and confirmed via Annexin V/PI staining and flow cytometry, accompanied by downregulation of Ccnd1 and Bcl2. Additionally, rosiglitazone markedly increased the expression of Cebpa, a key regulator that can modulate lipid droplet formation and the balance between cell growth and death. Conclusions: Rosiglitazone and betulinic acid differentially modulate adipogenesis and apoptosis in 3T3-L1 cells, revealing a complex interplay between lipid accumulation and programmed cell death. Together, the findings underscore the potential of dual PPARG-targeting approaches for metabolic disease interventions. Full article

MicroRNAs play a pivotal role in the regulation of adipose tissue function and have emerged as promising therapeutic candidates for the management of obesity and associated comorbidities. Among them, miR-1 could be a potential biomarker for metabolic diseases and contribute to metabolic homeostasis. However, thorough research is required to fully elucidate the impact of miR-1 on human adipocyte thermogenesis and metabolism. This study aimed to explore the effect of miR-1 on human adipocyte browning, a process whose activation has been linked to obesity protection and counteraction. Human multipotent adipose-derived stem cells, hMADS cells, were differentiated into white and brown-like adipocytes and transfected with miR-1 mimics for gene expression and western blotting analyses. miR-1 inhibited the expression of its previously validated target PTK9/TWF1 and modulated the expression profile of key genes involved in thermogenesis and adipocyte browning (increased UCP1 at mRNA and protein level, increased CPT1M, decreased HIF3A), adipocyte differentiation and metabolism (decreased PLIN1, FASN, RXRA, PPARG, FABP4, MAPKAPK2), as well as genes related to the cytoskeleton (decreased ACTB) and extracellular matrix (decreased COL1A1). These findings suggest that miR-1 can modulate the expression of adipocyte human genes associated with thermogenesis and metabolism, which could hold value for eventual therapeutic potential in obesity. Full article