PubMed

Int J Mol Sci. 2025 Feb 28;26(5):2220. doi: 10.3390/ijms26052220.ABSTRACTColorectal cancer (CRC) is the second deadliest cancer in the Western world. Increased body weight, a diet rich in red meat and alcohol, as well as a sedentary lifestyle, are all involved in sporadic CRC pathogenesis. Since current CRC therapies show several side effects, there is a need to find new and more effective therapeutic approaches, allowing conventional drug dosages and toxicity to be reduced. Gratiola officinalis alcoholic extract was characterized by LC-MS and its effect investigated on a healthy colon mucosa cell line and on different colorectal cancer cell lines. Cell viability, apoptosis and cell cycle progression were evaluated through flow cytometry; energy production and glycolysis were investigated using Seahorse technology, while cancer markers were analyzed through Western blotting. The untargeted metabolomics analysis of G. officinalis alcoholic extract revealed glycosides of different polyphenols and glycosides of cucurbitane-type triterpenes. This extract showed a stronger impact on CRC cell line viability compared to healthy colon cells. In the E705 CRC cell line, it induced cell apoptosis and caused the downregulation of glycolysis, inhibiting cell proliferation. On the other hand, SW480 CRC cells treated with G. officinalis extract showed G2/M cell cycle arrest. This work shows that G. officinalis extract can reduce glycolysis and promote cell cycle arrest in CRC cells, suggesting that G. officinalis could represent a novel player in the prevention and treatment of CRC.PMID:40076837 | DOI:10.3390/ijms26052220

Int J Mol Sci. 2025 Feb 28;26(5):2201. doi: 10.3390/ijms26052201.ABSTRACTCyanobacteria isolated from extreme habitats are promising in biotechnology due to their high adaptability to unfavorable environments and their specific natural products. Therefore, these organisms are stored under a reduced light supply in multiple collections worldwide. However, it remains unclear whether these strains maintain constitutively expressed primary metabolome features associated with their unique adaptations. To address this question, a comparative analysis of primary metabolomes of twelve cyanobacterial strains from diverse extreme habitats was performed by a combined GC-MS/LC-MS approach. The results revealed that all these cyanobacterial strains exhibited clear differences in their patterns of primary metabolites. These metabolic differences were more pronounced for the strains originating from ecologically different extreme environments. Extremotolerant terrestrial and freshwater strains contained lower strain-specifically accumulated primary metabolites than extremophilic species from habitats with high salinity and alkalinity. The latter group of strains was highly diverse in amounts of specific primary metabolites. This might indicate essentially different molecular mechanisms and metabolic pathways behind the survival of the microorganisms in saline and alkaline environments. The identified strain-specific metabolites are discussed with respect to the metabolic processes that might impact maintaining the viability of cyanobacteria during their storage and indicate unique adaptations formed in their original extreme habitats.PMID:40076823 | DOI:10.3390/ijms26052201

Int J Mol Sci. 2025 Feb 27;26(5):2151. doi: 10.3390/ijms26052151.ABSTRACTThis study investigates the interplay between volatile and non-volatile flavor metabolites and endophytic microbial communities during three developmental stages of Passiflora ligularis fruit juice. Using bioinformatics and metabolomics, we characterize microbial diversity and metabolic variations to understand flavor development. A total of 1490 bacterial and 1158 fungal operational taxonomic units (OTUs) were identified. Young fruits had higher microbial diversity, dominated by Proteobacteria and Firmicutes (bacteria) and Ascomycota and Basidiomycota (fungi). As the fruit matured, Proteobacteria increased while Firmicutes decreased, indicating that microbial succession is tied to development. Metabolomic profiling identified 87 volatile and 1002 non-volatile metabolites, with distinct chemical classes varying across stages. Saturated hydrocarbons and fatty alcohols were the main volatile metabolites, while organic acids and lipids among non-volatile metabolites showed stage-dependent changes, influencing flavor complexity. Correlation analysis showed microbial-flavor interactions: Proteobacteria negatively correlated with metabolites, while Firmicutes positively correlated with metabolites. Ascomycota positively correlated with volatile metabolites, whereas Basidiomycota showed an inverse relationship, highlighting their differential contributions to flavor biosynthesis. This study enhances understanding of microbial and metabolic factors shaping P. ligularis fruit flavor, highlighting the importance of microbial influence on fruit metabolomics. The findings suggest the potential for microbiome engineering to improve flavor quality, aiding postharvest management and industrial processing in the food and beverage industry.PMID:40076773 | DOI:10.3390/ijms26052151

Int J Mol Sci. 2025 Feb 27;26(5):2150. doi: 10.3390/ijms26052150.ABSTRACTInvertase (INV, EC3.2.1.26) is widely recognized as an indispensable enzyme for catalyzing sucrose degradation and plays a central role in plant growth as well as fruit quality improvement. However, no systematic study has been performed in kiwifruit. Here, we identified 102 AaINV genes in the Actinidia arguta "M1" genome. Their physical and chemical properties, subcellular localizations, phylogenetic relationships and expression profiles were characterized. Phylogenetic analysis showed that the INV members were clustered into three groups (vacuole invertases (VINVs) and cell wall invertases (CWINVs) in Group I, alkaline/neutral invertase (NINVs) in Group II and Group III), demonstrating evolutionary conservation in the INV family across Arabidopsis and Actinidia species. Gene replication analysis revealed that many AaINV genes were derived from gene duplication events. Molecular evolution analysis based on Ka/Ks ratios indicated that the INV members have experienced extensive purifying selection during evolution. To explore the potential gene functions, we integrated RNA-seq and metabolomics to analyze AaINV gene expression patterns and sugar accumulation in three A. arguta varieties ("Kukuwa", "Qinhuang", "Xianziguang"), respectively. The expression analysis of the 102 genes showed that the expression patterns varied among the three kiwifruit varieties at fruit maturity stage. The expression levels of AaINVs were also investigated via qRT-PCR in these varieties. Specifically, we constructed a complex regulatory network that regulates sugar metabolism in kiwifruit based on the correlation between 42 AaINV genes and 14 sugar metabolites. These findings provide insights into physiological functions of AaINVs in kiwifruit, especially roles in governing sugars accumulation in fruits.PMID:40076770 | DOI:10.3390/ijms26052150

Int J Mol Sci. 2025 Feb 27;26(5):2111. doi: 10.3390/ijms26052111.ABSTRACTInflammatory bowel disease is a risk factor for brain dysfunction; however, the underlying mechanisms remain largely unknown. In this study, we aimed to explore the potential molecular mechanisms through which intestinal inflammation affects brain function and to verify these mechanisms. Mice were treated with multiple cycles of 1% w/v dextran sulfate sodium (DSS) in drinking water to establish a chronic colitis model. Behavioral tests were conducted using the open field test (OFT), tail suspension test (TST), forced swimming test (FST), and Morris water maze test (MWM). Brain metabolomics, transcriptomics, and proteomics analyses were performed, and key target proteins were verified using qPCR and immunofluorescence. Four cycles of DSS administration induced colitis, anxiety, depression, and spatial memory impairment. The integrated multi-omics characterization of colitis revealed decreased brain chenodeoxycholic acid (CDCA) levels as well as reduced stearoyl-CoA desaturase (Scd1) gene and protein expression. Transplantation of the colitis microbiome resulted in anxiety, depression, impaired spatial memory, reduced CDCA content, decreased Scd1 gene and protein expression, and lower concentrations of monounsaturated fatty acids (MUFAs), palmitoleate (C16:1), and oleate (C18:1) in the brain. In addition, CDCA supplementation improved DSS-induced colitis, alleviated depression and spatial memory impairment, and increased Scd1 gene and protein expression as well as MUFA levels in the brain. The gut microbiome induced by colitis contributes to neurological dysfunction, possibly through the CDCA-Scd1 signaling axis. CDCA supplementation alleviates colitis and depressive behavior, likely by increasing Scd1 expression in the brain.PMID:40076732 | DOI:10.3390/ijms26052111

Int J Mol Sci. 2025 Feb 27;26(5):2102. doi: 10.3390/ijms26052102.ABSTRACTThe diagnosis of heart failure with preserved ejection fraction (HFpEF) remains challenging. The use of metabolomics approaches seems promising in speeding up and simplifying the diagnostic process in HFpEF patients, which can lead to earlier treatment initiation and better improvement of patient condition. The aim of this study was to develop a diagnostic panel of metabolites (metabolomic biomarkers) for the detection and diagnosis of HF with preserved ejection fraction. The study included 76 participants with hypertension, 36 of whom were diagnosed with HFpEF. The blood plasma metabolomic profile, including 72 metabolites, was detected using high-performance liquid chromatography combined with mass spectrometry. There were 18 statistically significant differences in concentrations of metabolites and 3 differences in their ratios between HFpEF and hypertension groups. The prognostic model for detecting the possibility of HFpEF included seven metabolites and two ratios: hexadecenoylcarnitine, arginine, trimethylamine-N-oxide, asymmetric dimethylarginine (ADMA), arginine/ADMA ratio, kynurenine, kynurenine/tryptophan, neopterin, and anthranilic acid. The area under the ROC curve was 0.981 ± 0.017. The resulting model was statistically significant (p < 0.001). The metabolomic panel could be considered as an addition to the present HFpEF laboratory diagnostic criteria for blood plasma analysis in clinical practice.PMID:40076723 | DOI:10.3390/ijms26052102

Int J Mol Sci. 2025 Feb 27;26(5):2095. doi: 10.3390/ijms26052095.ABSTRACTThe target of rapamycin (TOR) kinase is an evolutionarily conserved atypical Ser/Thr protein kinase present in yeasts, plants, and mammals. In plants, TOR acts as a central signaling hub, playing a pivotal role in the precise orchestration of growth and development. Extensive studies have underscored its significant role in these processes. Recent research has further elucidated TOR's multifaceted roles in plant stress adaptation. Furthermore, mounting evidence indicates TOR's role in mediating the plant metabolome. In this review, we will discuss recent findings on the involvement of TOR signaling in plant adaptation to various abiotic and biotic stresses, with a specific focus on TOR-regulated metabolome reprogramming in response to different stresses.PMID:40076716 | DOI:10.3390/ijms26052095

Int J Mol Sci. 2025 Feb 26;26(5):2059. doi: 10.3390/ijms26052059.ABSTRACTAlzheimer's disease (AD) is characterized by progressive cognition and behavior impairments. Diagnosing AD early is important for clinicians to slow down AD progression and preserve brain function. Biomarkers such as tau protein and amyloid-β peptide (Aβ) are used to aid diagnosis as clinical diagnosis often lags. Additionally, biomarkers can be used to monitor AD status and evaluate AD treatment. Clinicians detect these AD biomarkers in the brain using positron emission tomography/computed tomography or in the cerebrospinal fluid using a lumbar puncture. However, these methods are expensive and invasive. In contrast, saliva collection is simple, inexpensive, non-invasive, stress-free, and repeatable. Moreover, damage to the brain parenchyma can impact the oral cavity and some pathogenic molecules could travel back and forth from the brain to the mouth. This has prompted researchers to explore biomarkers in the saliva. Therefore, this study provides an overview of the main finding of salivary biomarkers for AD diagnosis. Based on these available studies, Aβ, tau, cholinesterase enzyme activity, lactoferrin, melatonin, cortisol, proteomics, metabolomics, exosomes, and the microbiome were changed in AD patients' saliva when compared to controls. However, well-designed studies are essential to confirm the reliability and validity of these biomarkers in diagnosing and monitoring AD.PMID:40076682 | DOI:10.3390/ijms26052059

Lett Appl Microbiol. 2025 Mar 12:ovaf037. doi: 10.1093/lambio/ovaf037. Online ahead of print.ABSTRACTBreast cancer has emerged as the leading cause of global cancer incidence, surpassing lung cancer. Accumulating evidence suggests that probiotics exhibit inhibitory effect on breast cancer progression, highlighting the need to identify gut flora-derived probiotics with potential anti-breast cancer properties. Here, we investigated the effect of the cell-free supernatant of C. leptum (ClCFS) on breast cancer cells by MTT assay. Untargeted metabolomics analysis was employed to characterize metabolite alterations in ClCFS. Furthermore, the core targets were predicted by the protein-protein interaction network and the signaling pathways were enriched by the Kyoto Encyclopedia of Genes and Genomes analysis. Our findings demonstrated that ClCFS inhibited the proliferation of breast cancer cells and that the main metabolite of ClCFS might be acetylcarnitine. Utilizing network pharmacological analysis, we identified apoptosis-related signaling pathways as the principal mechanisms underlying ClCFS activity. Furthermore, five core targets of STAT3, IL-1β, BCL2, CASP3, and ESR1 were identified. This study elucidates the main bioactive constituent and the potential targets of ClCFS against breast cancer. It provides a new understanding of the pharmacological activity of ClCFS in breast cancer treatment.PMID:40074544 | DOI:10.1093/lambio/ovaf037

Lupus Sci Med. 2025 Mar 12;12(1):e001197. doi: 10.1136/lupus-2024-001197.ABSTRACTOBJECTIVE: The objective of this research is to identify metabolic markers associated with successful treatment by evaluating the effect of mesenchymal stem cell transplantation (MSCT) on the metabolic profiles of patients with SLE.METHODS: Plasma samples were collected from 20 patients with SLE before and after MSCT. Principal component analysis (PCA) was used to distinguish pretreatment and post-treatment groups and pathway analysis for identifying involved metabolic pathways. Clinical variables were monitored with a median follow-up time of 180 days. Pearson correlation and receiver operating characteristics (ROC) analysis were employed to associate metabolite changes with clinical outcomes and to predict treatment success.RESULTS: We detected 18 121 metabolites, with 1152 showing significant changes post-treatment, which could be clearly distinguished between pretreatment and post-treatment groups through PCA. Pathway analysis indicated involvement in riboflavin and thiamine metabolism. Clinical improvements were observed at a median follow-up time of 180 days after MSCT, including decreased SLE Disease Activity Index scores, urine protein/creatinine ratios, and erythrocyte sedimentation rates, along with increased levels of complement C3 and C4, haemoglobin, and platelets. Pearson correlation indicated that specific metabolite changes were associated with clinical improvements, particularly increases in thiamine monophosphate (TMP) and asiaticoside levels. ROC analysis identified TMP level changes as the most predictive of treatment success, with a 35% increase indicating a good response to MSCT.CONCLUSION: This study concludes that TMP is a potential biomarker that can predict the efficacy of MSCT in treating SLE, providing valuable insights for clinical practice and further research.PMID:40074250 | DOI:10.1136/lupus-2024-001197

J Phycol. 2025 Mar 12. doi: 10.1111/jpy.70001. Online ahead of print.ABSTRACTThe interdependence between microalgae and bacteria has sparked scientific interest over years, primarily driven by the practical applications of microalgal-bacteria consortia in wastewater treatment and algal biofuel production. Although adequate studies have focused on the broad interactions and general behavior between the two entities, there remains a scarcity of study on the metabolic role of symbiotic bacteria in promoting microalgal growth. Here, we use the KEIO Knockout Collection, an Escherichia coli gene knockout mutant library, to systematically screen for genes involved in the interdependence of Chlorella sorokiniana and E. coli. By co-cultivating C. sorokiniana and E. coli knockout mutants in 96-well microplates (200 μL medium per well) under white light at 25°C, 31 potential algal growth-promoting and 56 growth-inhibiting genes out of 3985 genes were identified that enhanced (≥1.25-fold) and diminished (≤0.8-fold) the production of algal chlorophyll-a content, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) mapping of these growth-regulating genes suggested a metabolic symbiosis involving bacteria-derived cobalamin (cobU, cobC), biotin (bioB, bioF, bioC, bioD, fabF, fabH), riboflavin (fbp, guaB, gnd, guaA, zwf, purA), and 2,3-butanediol (fumB, adhE, mdh, frdB, pta, sdhC). The effects of these metabolites were further validated by supplementing the agents into the axenic algal cultures; Dose-dependent trends were observed for each metabolite, with a maximum four-fold increase in algal biomass productivity over the control. The specific growth rate of algae was increased by ≥1.27-fold and doubling time was shortened by ≥22.5%. The present results, obtained through genome-wide analyses of interdependence between microalgae and bacteria, reveals multiple interactions between organisms via metabolites.PMID:40074247 | DOI:10.1111/jpy.70001

Int J Biol Macromol. 2025 Mar 10:141933. doi: 10.1016/j.ijbiomac.2025.141933. Online ahead of print.ABSTRACTType 3 resistant starch (RS3) regulates diet-related metabolic diseases by promoting intestinal short-chain fatty acids (SCFAs) and lactate production, and facilitating microbial lactate-to-butyrate fermentation. However, its precise in vivo mechanism remains unclear. Therefore, we studied the effects of type 3 lotus seed resistant starch (LRS3) and sodium lactate (SL) on colonic microbiota composition, metabolism, and lipid parameters. This study aimed to elucidate the mechanism by which LRS3 and SL modulate colonic microbiota and metabolism to mitigate hyperlipidemia in rats induced by a high-fat diet. Results showed LRS3 increased colonic microbial diversity, shifting the composition towards that of healthy rats. LRS3 intake reduced lactic acid-producing bacteria such as Allobaculum, Collinsella, and Blautia in the colon while promoting SCFAs-producing Ruminococcaceae. SL alone stimulated Lachnospiraceae growth. When both were administered, there was a significant increase in Treponema and Ruminococcaceae. The co-intervention of LRS3 and SL significantly affected lipid metabolism-related metabolites, up-regulating palmitic acid while down-regulating androsterone and phosphatidylcholine (PC) substances PC (14:0/20:4(8Z,11Z,14Z,17Z)), influencing unsaturated fatty acid biosynthesis pathways and inhibiting steroid hormone biosynthesis. Finally, via the microbial-metabolism-lipid correlation network, we identified that LRS3 and SL increased SCFAs production through Treponema and Ruminococcaceae metabolism, influencing organic acid and lipid composition in the colon. This indirectly reduced blood lipid levels in hyperlipidemic rats by modulating intestinal microecology.PMID:40074132 | DOI:10.1016/j.ijbiomac.2025.141933

J Ethnopharmacol. 2025 Mar 10:119616. doi: 10.1016/j.jep.2025.119616. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: 5-Fluorouracil (5-FU) commonly induces severe mucositis, causing pain, inflammation, and gastrointestinal dysfunction, which significantly increases patient morbidity and reduces quality of life. In Ayurveda, Traditional Chinese Medicine, and other ethnopharmacological practices, dried ginger has been widely used to alleviate symptoms such as nausea, vomiting, diarrhea, and inflammation, highlighting its important role in traditional medicine.AIM OF THE STUDY: This study explored the potential of dried ginger essential oil (DGEO) in mitigating intestinal epithelial barrier damage in mice with mucositis induced by 5-FU.METHODS: The therapeutic effects of DGEO were evaluated by measurements of weight changes, diarrhea scores, ELISA, and H&E. Further investigations included 16S rRNA sequencing, untargeted metabolomics, molecular docking, and HPLC-MS/MS to explore its underlying mechanisms, with validation performed using western blotting and ELISA.RESULTS: The results demonstrated that DGEO was effective in alleviating mucositis symptoms.It also improved the gut microbiota, enhanced the biotransformation of tryptophan to indole-3-acetic acid (IAA), and elevated the protein expressions of the AHR, CYP1A1, and p-STAT3, as well as levels of IL-22. Moreover, DGEO improved the expression of tight junction(TJ) proteins and anti-apoptotic proteins, enhancing intestinal barrier integrity.CONCLUSION: These findings indicated that DGEO ameliorated 5-FU-induced mucositis by modulating gut microbiota and the tryptophan metabolite IAA-AHR/IL-22/STAT3 signaling axis, providing new insights into its therapeutic applications, particularly its ability to regulate gut microbiota and related signaling pathways.PMID:40074099 | DOI:10.1016/j.jep.2025.119616

J Biol Chem. 2025 Mar 10:108398. doi: 10.1016/j.jbc.2025.108398. Online ahead of print.ABSTRACTPyruvate dehydrogenase kinase (PDK) 1 is one of four isozymes that inhibit the oxidative decarboxylation of pyruvate to acetyl-CoA via pyruvate dehydrogenase. PDK activity is elevated in fasting or starvation conditions to conserve carbohydrate reserves. PDK has also been shown to increase mitochondrial fatty acid utilization. In cardiomyocytes, metabolic flexibility is crucial for the fulfillment of high energy requirements. The PDK1 isoform is abundant in cardiomyocytes, but its specific contribution to cardiomyocyte metabolism is unclear. Here we show that PDK1 regulates cardiomyocyte fuel preference by mediating triacylglycerol turnover in differentiated H9c2 myoblasts using lentiviral shRNA to knockdown Pdk1. Somewhat surprisingly, PDK1 loss did not affect overall PDH activity, basal glycolysis, or glucose oxidation revealed by oxygen consumption rate experiments and 13C6 glucose labelling. On the other hand, we observed decreased triacylglycerol turnover in H9c2 cells with PDK1 knockdown, which was accompanied by decreased mitochondrial fatty acid utilization following nutrient deprivation. 13C16 palmitate tracing of uniformly labelled acyl chains revealed minimal acyl chain shuffling within triacylglycerol, indicating that the triacylglycerol hydrolysis, and not re-esterification, was dysfunctional in PDK1 suppressed cells. Importantly, PDK1 loss did not significantly impact the cellular lipidome or triacylglycerol accumulation following palmitic acid treatment, suggesting that effects of PDK1 on lipid metabolism were specific to the nutrient-deprived state. We validated that PDK1 loss decreased triacylglycerol turnover in Pdk1 knockout mice. Together, these findings implicate a novel role for PDK1 in lipid metabolism in cardiomyocytes, independent of its canonical roles in glucose metabolism.PMID:40074083 | DOI:10.1016/j.jbc.2025.108398

Metabolism. 2025 Mar 10:156189. doi: 10.1016/j.metabol.2025.156189. Online ahead of print.ABSTRACTBACKGROUND: Triacylglycerol (TAG) plasma excursions after a high-fat meal are blunted after Roux-en-Y gastric bypass (RYGB), but underlying mechanisms are poorly understood. We studied TAG absorption and metabolism in 12 RYGB-operated individuals and 12 unoperated controls (CON) matched on sex, age, and BMI.METHODS: Participants followed a 7-day controlled diet and on day 4 underwent 1H-MR Spectroscopy of liver TAG and a high-fat liquid meal with oral and intravenous labeled stable isotope metabolites, subcutaneous abdominal fat biopsies, and indirect calorimetry. Subsequently, participants collected stool for 96 h.RESULTS: Overall fat absorption from the controlled diet was moderately lower in RYGB than CON (88 % versus 93 %, P < 0.01), without indication of greater specific malabsorption of fat from the high-fat test meal (recovery of TAG and labeled TAG in 96-hour stool samples). After an overnight fast, plasma TAG concentrations and incorporation of plasma fatty acids (IV tracer) into TAG did not differ between groups. The postprandial 6-hour iAUC of plasma TAG plasma concentrations was markedly lower in RYGB than CON (15 versus 70 mmol/L × min, P = 0.03). The postprandial chylomicron (CM) particle response (plasma ApoB48) was initially higher in RYGB, but with lower CM-TAG plasma concentrations and appearance of labeled palmitate from the oral tripalmitin tracer over the 6 h.CONCLUSION: Fat absorption is only moderately lower after RYGB compared with unoperated matched controls. Nevertheless, postprandial TAG and CM plasma kinetics after a high-fat meal are markedly altered after RYGB with substantially lower TAG and CM-TAG concentrations despite a faster CM particle release.PMID:40074057 | DOI:10.1016/j.metabol.2025.156189

Phytomedicine. 2025 Mar 6;140:156622. doi: 10.1016/j.phymed.2025.156622. Online ahead of print.ABSTRACTBACKGROUND: Hyperuricemia (HUA) is a metabolic disease disturbing human health caused by the overproduction or underexcretion of uric acid (UA). Astragalus is the root of Astragalus membranaceus (Fisch.) Bunge, has notable regulatory effect on chronic nephritis, proteinuria and spontaneous sweating, suggesting it could be a potential anti-HUA agent. However, limited research has been conducted on its anti-HUA effect and mechanism.METHODS: The present study performed untargeted and plasma metabolomics of Astragalus extract to identify the main constituents that can be absorbed and exert effect in mice, and further investigated the underlying mechanism by enzyme activity assay, Western Blotting and molecular docking.RESULTS: The results showed that Astragalus flavone extract inhibited UA synthesis by binding to XOD to hinder substrate binding and inhibiting xanthine oxidase (XOD) protein expression, inhibited JNK/AP-1/NLRP3/IL-1β signaling pathway to alleviate prolonged HUA-induced inflammation and abnormal UA metabolism, and protected the kidney by reducing serum renal function index and improving renal tissue atrophy, fibrosis and tubular dilatation both in vitro and in vivo. Besides, glycitein and isoformononet were identified as the main flavones in Astragalus extract absorbed into the bloodstream of mice, isoformononetin was found to inhibit UA synthesis by direct binding to XOD, and glycitein was found to interact with c-Jun to facilitate UA excretion and inhibit inflammation.CONCLUSION: This paper represents the pioneering investigation that firstly identifying two flavonoids of Astragalus extract that can be absorbed to fight against HUA, and elucidating their diverse molecular mechanism by targeting JNK/AP-1/NLRP3/IL-1β signaling pathway, UA metabolism and kidney protection.PMID:40073779 | DOI:10.1016/j.phymed.2025.156622

Phytomedicine. 2025 Mar 7;140:156526. doi: 10.1016/j.phymed.2025.156526. Online ahead of print.ABSTRACTBACKGROUND: The coastal wetland mangrove plant Acanthus ilicifolius l. (AI) is used as traditional medicine for liver protection and liver fibrosis treatment, but the pharmacodynamics of the hepatoprotective substance and the mechanisms of liver protection are not clear.PURPOSE: This work aimed to assess the liver-protective ability of AI and elucidate the pharmacodynamics of the hepatoprotective substance of AI responsible for its liver activity.STUDY DESIGN AND METHODS: This study first appraised the hepatoprotective activity of the alcohol extract of AI. To identify the hepatoprotective substance in AI, network topology and the contribution index were comprehensively analyzed and screened. The screened medicinal substances, acteoside (ACT) and isoacteoside (IACT), were tested for hepatoprotective activity using mouse liver damage model and l-02 hepatocyte injury model, and metabolomics was employed to explore the mechanism of liver protection.RESULTS: AI could restore the biochemical indicators of liver damage induced by CCl4 to normal conditions. The phenylethanoid glycoside compounds ACT and IACT, are the hepatoprotective substances of AI. ACT protects the liver tissue by regulating α-linolenic acid metabolism, glycerophospholipid metabolism, and amino acid-related pathway.CONCLUSION: This research provides basic information of the research and development of liver-protective effects of AI and ACT.PMID:40073778 | DOI:10.1016/j.phymed.2025.156526

Redox Biol. 2025 Mar 5;81:103582. doi: 10.1016/j.redox.2025.103582. Online ahead of print.ABSTRACTAnaplastic Large Cell Lymphoma (ALCL) is an aggressive T-cell lymphoma affecting children and young adults. About 30% of patients develop therapy resistance therefore new precision medicine drugs are highly warranted. Multiple rounds of structure-activity optimization of Caffeic Acid Phenethyl Ester have resulted in CM14. CM14 causes upregulation of genes involved in oxidative stress response and downregulation of DNA replication genes leading to G2/M arrest and subsequent apoptosis induction. In accordance with this, an unbiased proteomics approach, confocal microscopy and molecular modeling showed that TUBGCP2, member of the centrosomal γ-TuRC complex, is a direct interaction partner of CM14. CM14 overcomes ALK inhibitor resistance in ALCL and is also active in T-cell Acute Lymphoblastic Leukemia and Acute Myeloid Leukemia. Interestingly, CM14 also induced cell death in docetaxel-resistant prostate cancer cells thus suggesting an unexpected role in solid cancers. Thus, we synthesized and thoroughly characterized a novel TUBGCP2 targeting drug that is active in ALCL but has also potential for other malignancies.PMID:40073758 | DOI:10.1016/j.redox.2025.103582

Plant Physiol Biochem. 2025 Mar 5;222:109755. doi: 10.1016/j.plaphy.2025.109755. Online ahead of print.ABSTRACTAlpinia oxyphylla Miq., a well-accepted medicinal and edible plant in south China. The primary ingredients of this medicine vary significantly depending on their origin, which profoundly impacts its quality. In this study, a principal component analysis was performed on 17 different planting areas of A. oxyphylla, with nootkatone and kaempferol identified as representative sesquiterpenoids and flavonoids, respectively. To investigate the genes involved in nootkatone and kaempferol biosynthesis, a combined transcriptome and metabolome profiling was carried out on materials sourced from geo-authentic and non-authentic areas. The transcriptome analysis of these two types of accessions identified 96,691 unigenes, with 13,589 genes showing differential expression in both regions. Metabolome analysis revealed 2859 differentially accumulated metabolites across the four pairwise comparisons. Correlation analysis uncovered a number of genes, that associated with the differential biosynthesis of nootkatone and kaempferol in A. oxyphylla fruits from geo-authentic and non-authentic areas. Further investigation highlighted the candidate gene AoFMO1's ability to heterologously biosynthesize nootkatone in Arabidopsis thaliana leaves. This research lays the groundwork for a deeper understanding of the molecular mechanisms behind the authentication of A. oxyphylla's quality synthesis, and presents a comprehensive list of candidate genes for future functional studies to enhance the development of high-quality A. oxyphylla varieties rich in medicinal ingredients.PMID:40073739 | DOI:10.1016/j.plaphy.2025.109755

Neurobiol Aging. 2025 Mar 8;150:69-79. doi: 10.1016/j.neurobiolaging.2025.03.004. Online ahead of print.ABSTRACTIncreasing age and elevated intraocular pressure (IOP) are the two major risk factors for glaucoma, the most common cause of irreversible blindness worldwide. Accumulating evidence is pointing to metabolic failure predisposing to neuronal loss with advancing age and IOP injury. Many neurotransmitters are synthesized from endogenous metabolites and are essential for correct cell to cell signaling along the visual pathways. We performed detailed, small molecule metabolomic profiling of the aging mouse retina and further explored the impact of IOP elevation at different ages. The resultant metabolomic profiles showed clear discrimination between young and middle-aged retinas and these changes are accentuated following eye pressure elevation. Alterations in glutamate and Gamma-aminobutyric acid (GABA) related metabolites were the most apparent changes with advancing age with further reductions in GABA and related pathways after IOP elevation. These changes were further confirmed using immunohistochemistry and patch-clamp electrophysiological recording experiments.PMID:40073716 | DOI:10.1016/j.neurobiolaging.2025.03.004