PubMed

Cell Mol Life Sci. 2025 Apr 17;82(1):163. doi: 10.1007/s00018-025-05680-2.ABSTRACTOBJECTIVE: Central precocious puberty (CPP) is a common pediatric endocrine disorder and a significant global public health concern. Emerging evidence suggests an association between bile acids (BAs) and CPP, although their regulatory roles and underlying mechanisms remain poorly understood.METHODS: We conducted untargeted metabolomics and targeted BA analysis on serum samples from female rats with high-fat diet-induced CPP to identify metabolites potentially involved in regulating puberty through modulation of Sirt1 and Kiss1 expression in the hypothalamus. Identified BAs were then administered via gavage to female rats with CPP to assess their effects. To explore the mechanisms by which these BAs affect the development of CPP, gut microbiota and their metabolites were analyzed using 16S rRNA sequencing and untargeted metabolomics.RESULTS: Our findings revealed significant reductions in glycodeoxycholic acid (GDCA) and glycoursodeoxycholic acid (GUDCA) levels in female rats with CPP. GDCA treatment delayed the onset of puberty, accompanied by alterations in the gut microbiota functions and metabolic pathways related to oxidative stress (OS) and fatty acid metabolism. Mediation analysis suggested that OS-related metabolites, including gamma-glutamylcysteine and malonic acid, which increased with the abundance of Lachnospiraceae UCG-001, facilitated the reduction of Sirt1 expression. Additionally, pregnenolone appeared to suppress the beneficial effect of Parasutterella in enhancing Sirt1 expression.CONCLUSION: This study demonstrates that GDCA exhibits a potential therapeutic effect on CPP through a unique mechanism that involves gut microbiota modulation, alterations in serum metabolites, and changes in the expression of key regulatory factors Sirt1.PMID:40244411 | DOI:10.1007/s00018-025-05680-2

Cell Mol Life Sci. 2025 Apr 17;82(1):160. doi: 10.1007/s00018-025-05689-7.ABSTRACTINTRODUCTION: Brain injury is a common sequela following cardiac arrest (CA), with up to 70% of hospitalized patients dying from it. Brain microvascular endothelial cells (BMVECs) play a crucial role in post-cardiac arrest brain injury (PCABI). However, the effects and mechanisms of targeting BMVEC energy metabolism to mitigate brain injury remain unclear.METHODS: We established a mouse model of cardiac arrest by injecting potassium chloride into the right internal jugular vein. Mass spectrometry detected targeted changes in short-chain fatty acids and energy metabolism metabolites in the CA/CPR group compared to the sham group. Mice with overexpressed ACSS2 in BMVECs were created using an AAV-BR1 vector, and ACSS2 knockout mice were generated using the CRE-LOXP system. The oxygen glucose deprivation/re-oxygenation (OGD/R) model was established to investigate the role and mechanisms of ACSS2 in endothelial cells in vitro.RESULTS: Metabolomics analysis revealed disrupted cerebral energy metabolism post-CA/CPR, with decreased acetyl-CoA and amino acids. Overexpression of ACSS2 in BMVECs increased acetyl-CoA levels and improved neurological function. Vascular endothelial cell-specific ACSS2 knockout mice exhibited reduced aortic sprouting in vitro. Overexpression of ACSS2 improved endothelial dysfunction following oxygen glucose deprivation/re-oxygenation (OGD/R) and influenced autophagy by interacting with transcription factor EB (TFEB) and modulating the AMP-activated protein kinase α (AMPKα) pathway.CONCLUSION: Our study shows that ACSS2 modulates the biological functions of BMVECs by promoting autophagy. Enhancing energy metabolism via ACSS2 may target PCABI treatment development.PMID:40244361 | DOI:10.1007/s00018-025-05689-7

Int J Mol Sci. 2025 Apr 4;26(7):3385. doi: 10.3390/ijms26073385.ABSTRACTMicroRNAs (miRNAs) are small non-coding RNAs involved in gene regulation and are potential biomarkers for several diseases, including canine enteropathies. While metabolite profiling and microbiome in canine enteropathies have been previously explored, data on miRNA expression remain limited. This study aimed to profile miRNA expression in Yorkshire Terrier canine enteropathy using Illumina sequencing and quantitative PCR (qPCR) to compare miRNA levels between sick and healthy dogs from fecal samples. Despite the hypothesis that disease-related alterations in miRNA levels would differentiate sick dogs from controls, no significant differences were observed between the groups in either sequencing or qPCR analyses. These findings suggest that miRNA profiles may not vary significantly in the context of Yorkshire Terrier enteropathy and indicate that other molecular or metabolomic markers may be more indicative of disease state. This study also indicates that fecal samples may not be an ideal sample type for miRNA profiling. This study contributes to the understanding of molecular signatures in canine enteropathies and provides a basis for further research into alternative biomarkers for diagnosis and monitoring.PMID:40244288 | DOI:10.3390/ijms26073385

Int J Mol Sci. 2025 Apr 3;26(7):3332. doi: 10.3390/ijms26073332.ABSTRACTAntimony and copper can contaminate vegetables and enter the human body through the digestive tract, inducing severe and extensive biotoxicity. However, the role of bile acids (BAs) in the pathogenesis of liver inflammation by antimony or copper has not been elucidated. Our results indicated that antimony and/or copper induced liver inflammation, causing the disruption of gut microbiota, with the down-regulation of probiotics and up-regulation of harmful bacteria closely correlated to liver inflammation. Targeted metabolomics of BAs showed that antimony and/or copper significantly up-regulated the levels of taurine-β-muricholic acid (T-β-MCA) in serum and liver, which was due to the reduction of Lactobacillus spp. A farnesoid X receptor (FXR) antagonist, T-β-MCA inhibited the FXR-SHP pathway in liver and FXR-FGF15 pathway in ileum, thereby promoting the transcription of cholesterol 7-alpha hydroxylase (CYP7A1) and increasing total bile acid concentrations, ultimately leading to liver inflammation. These findings provide new insights into the underlying mechanisms of antimony- and/or copper-induced liver inflammation.PMID:40244173 | DOI:10.3390/ijms26073332

Int J Mol Sci. 2025 Apr 2;26(7):3300. doi: 10.3390/ijms26073300.ABSTRACTCistanche deserticola, a holoparasitic plant widely used in traditional Chinese medicine, relies on chemical signals from its host plant, Haloxylon ammodendron, to initiate seed germination and haustorium induction. This study employed UPLC-MS/MS to analyze the root metabolites of H. ammodendron. The results showed that 11 substances such as phenolic acids, flavonoids, and alkaloids were mainly contained in the roots of H. ammodendron, among which phenolic acids accounted for the largest proportion, accounting for 18.00% in winter samples and 16.11% in autumn samples. Based on the reported exogenous substances that promote haustorium induction in C. deserticola and the differential metabolites in H. ammodendron roots, we selected seven exogenous signaling substances: 2,6-dimethoxy-1,4-benzoquinone, resorcinol, ferulic acid, syringic acid, vanillic acid, vanillin, and pelargonidin. Through concentration-gradient experiments (0.1-100 μM), we assessed their effects on haustorium induction in C. deserticola seeds. The results showed that among the seven substances, syringic acid, vanillic acid, and vanillin had the best impact on promoting the haustorium induction of C. deserticola seeds. Vanillic acid had the best impact at the concentration of 10 μmol/L, and the highest haustorium induction rate was 50.2%. There was no significant difference in the concentrations of vanillin and syringic acid. The results showed that phenolic acids in the host root system stimulated haustoria induction in C. deserticola seeds, with different substances requiring different optimal concentrations. This study not only identifies specific phenolic acids that enhance C. deserticola productivity but also establishes a chemical ecology framework for investigating host-parasite interactions in other root parasitic species.PMID:40244150 | DOI:10.3390/ijms26073300

Int J Mol Sci. 2025 Apr 2;26(7):3298. doi: 10.3390/ijms26073298.ABSTRACTInnovations in spinal cord injury (SCI) models are crucial for developing effective therapies. This study introduces a novel in vitro SCI model using cultures of primary mixed spinal cord cells from rat pups, featuring key spinal cord cell types. This model offers distinct advantages in terms of feasibility, reproducibility, and cost-effectiveness, requiring only basic cell culture equipment. Following hyperosmotic stress via sorbitol treatment, the model recapitulated SCI pathophysiological hallmarks, with a 65% reduction in cell viability and gradual cell death over 48 h, making it ideal for evaluating neuroprotective agents. Notably, the human adipose tissue stem cell (hASC) secretome provided significant protection: it preserved metabolic viability, reduced β amyloid precursor protein (β-APP) expression in surviving neurons, and modulated the shift in the astrocytic morphotype. A transcriptomic profile of the effect of the hASC secretome treatment showed significant functional enrichments related to cell proliferation and cycle progression pathways. In addition to supporting the use of the hASC secretome as a therapy for SCI, this study is the first to use sorbitol as a hyperosmolar stressor to recapitulate key aspects of SCI pathophysiology. Thereby, this model can be used as a promising platform for evaluating therapeutic agents targeting neuroprotection and neuroregeneration, offering outputs related to cell death, neuronal stress, and protection, as well as induction of glial reactivity.PMID:40244122 | DOI:10.3390/ijms26073298

Int J Mol Sci. 2025 Mar 31;26(7):3248. doi: 10.3390/ijms26073248.ABSTRACTAnorexia nervosa (AN) is a severe psychiatric disorder characterized by substantial heritability and a high mortality rate among psychiatric disorders. While cerebrospinal fluid (CSF) metabolomics has emerged as a novel approach to investigating central nervous system pathologies, its specific causal relationship with anorexia nervosa remains to be fully elucidated. Using genome-wide association study (GWAS) summary statistics for human CSF metabolites and AN information from publicly available datasets, we performed a two-sample Mendelian randomization (MR) analysis using the inverse-variance weighted (IVW) method as the primary approach, complemented by sensitivity analyses. Through a comprehensive analysis of 338 CSF metabolites, we identified six metabolites with significant causal relationships with AN risk. 1-stearoyl-2-linoleoyl-gpc (18:0/18:2) (OR = 1.09, 95% CI 1.00-1.18) and alpha-tocopherol (OR = 1.36, 95% CI 1.00-1.83) showed positive associations, increasing AN risk. Conversely, sphingomyelin (d18:1/20:0, d16:1/22:0) (OR = 0.86, 95% CI 0.77-0.95), 2,3-dihydroxy-2-methylbutyrate (OR = 0.92, 95% CI 0.86-0.98), N-acetylhistidine (OR = 0.92, 95% CI 0.86-0.98), and oxalate (ethanedioate) (OR = 0.83, 95% CI 0.73-0.94) had protective effects, reducing AN risk. Sensitivity analyses showed no evidence of horizontal pleiotropy or heterogeneity in the MR results. An MR directionality test and a Steiger filtering test confirmed the absence of reverse causality, thereby substantiating the robustness of our findings. These findings suggest that these CSF metabolites could serve as potential biomarkers for early AN detection and highlight novel therapeutic targets, potentially improving diagnosis and intervention strategies for this challenging disorder.PMID:40244111 | DOI:10.3390/ijms26073248

Biol Reprod. 2025 Apr 17:ioaf085. doi: 10.1093/biolre/ioaf085. Online ahead of print.ABSTRACTPlacental dysfunction is implicated in the pathogenesis of spontaneous preterm birth (SPTB). We investigated race (self-identified maternal race) and fetal sex differences in the placental metabolome and transcriptome associated with early SPTB (< 32 weeks). Long-chain polyunsaturated fatty acids, acylcarnitines, acylglycerols, plasmalogens, and lysophospholipids were remarkably different between SPTB and Term placentas. These alterations were much more profound in Black than White SPTB placentas. Mode of delivery and BMI had no effect on these differences. The lipid metabolic pathways disrupted in early SPTB placentas also exhibited fetal sex differences, particularly between Black male and Black female placentas. Expression of genes involved in multiple lipid metabolism regulating pathways (e.g. PI3K/AKT signaling and phospholipase activity), especially eicosanoid synthesis and secretion, were significantly altered in early SPTB placentas. The race- and sex-specific changes in lipid metabolites and gene expression were consistent with inflammation in SPTB placentas, which was further supported by dysregulation of various inflammation and immune response pathways. These findings reveal race and fetal sex differences in lipid metabolism and inflammation in SPTB placentas and suggest greater dysfunction and inflammation in Black compared to White SPTB placentas, which may explain mechanisms underlying early SPTB and the risk of SPTB in different populations.PMID:40244074 | DOI:10.1093/biolre/ioaf085

Int J Mol Sci. 2025 Mar 28;26(7):3133. doi: 10.3390/ijms26073133.ABSTRACTLitopenaeus vannamei is a key economic species in aquaculture, yet the molecular mechanisms underlying its growth variability remain unclear. This study conducted transcriptomic and metabolomic analyses of fast-growing (NL) and slow-growing (NS) shrimp under identical conditions. A total of 1280 differentially expressed genes (DEGs) related to protein processing, ribosomes, and oxidative phosphorylation, along with 5297 differentially abundant metabolites (DMs) involved in arginine biosynthesis, amino acid metabolism, and pantothenate and CoA biosynthesis, were identified and analyzed. An integrative analysis revealed that the NL shrimp exhibited an enhanced retinol, glutathione, riboflavin, and purine metabolism, which implies a higher tolerance to environmental stress. In contrast, the NS shrimp showed increased fatty acid degradation and an accelerated TCA cycle. This suggests that NS shrimp might require a substantial amount of energy to cope with environmental changes, consequently resulting in increased energy expenditures. This study provides significant insights into the molecular mechanisms underlying the growth disparity in L. vannamei, offering valuable data for future research aimed at optimizing shrimp growth performance and enhancing aquaculture productivity.PMID:40243931 | DOI:10.3390/ijms26073133

Int J Mol Sci. 2025 Mar 28;26(7):3120. doi: 10.3390/ijms26073120.ABSTRACTAmong the emerging threats in global health, fungal pathogens stand out as some of the most important, causing over 1.6 million deaths annually and destroying a third of all food crops each year, exacerbating food insecurity and economic losses. Climate change further amplifies the threat by enabling pathogenic fungi to survive at mammalian temperatures, increasing risks of zoonotic transmission and antifungal resistance. In this context, interdisciplinary research, particularly the One Health approach, is crucial for understanding the evolution of fungal resistance and improving diagnostic and therapeutic tools. Drawing lessons from agriculture, where integrated pest management strategies successfully mitigate fungal threats, could offer new ways to tackle fungal infections in humans. Advanced metabolomics and diagnostics, including fungal metabolites as biomarkers, hold promise for early detection and personalized treatment. Collaborative efforts between medicine, veterinary science, and plant pathology are essential to develop new antifungal drugs and improve clinical management of fungal diseases, fostering a more resilient global health system.PMID:40243890 | DOI:10.3390/ijms26073120

Int J Mol Sci. 2025 Mar 27;26(7):3105. doi: 10.3390/ijms26073105.ABSTRACTSafflower (Carthamus tinctorius L.) is a versatile oilseed crop valued for its adaptability, high oil quality, and antioxidant properties. This study investigates the influence of flower color (FC) on the phenotypic diversity of 172 safflower accessions, analyzing agronomic traits, metabolite profiles, and antioxidant capacities. Frequency distribution, effect size, principal component analysis (PCA), and network analysis were employed to elucidate trait associations and interrelationships. FC significantly impacted traits such as oleic acid (OA), linoleic acid (LA), oleic desaturation ratio (ODR), and N-feruloylserotonin (FS), with large effect sizes (η2 > 0.16). Medium effects were observed for 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) scavenging capacity, palmitic acid (PA), and flowering date (FD). PCA and network analyses highlighted relationships between FC and other fatty acid and antioxidant traits. Qualitative traits such as seed coat color (SCC) and thorn of involucre (TI) also showed significant associations with FC, underscoring its role as a phenotypic marker. These findings provide a robust framework for trait-based breeding strategies in safflower and emphasize the need for further genetic validation of these associations.PMID:40243856 | DOI:10.3390/ijms26073105

J Cell Biol. 2025 Jun 2;224(6):e202407198. doi: 10.1083/jcb.202407198. Epub 2025 Apr 17.ABSTRACTPeroxisomes are integral metabolic organelles involved in both catabolic and anabolic processes in humans, with defects linked to diseases. The functions of peroxisomes are regulated at transcriptional, translational, and posttranslational levels. In this study, we employed the CRISPR/Cas9-based screening of a ubiquitin ligase library to identify regulators of human peroxisomes. We discovered that ZBTB17 (MIZ1) plays a role in regulating the import of proteins into peroxisomes. Independent of its ubiquitin ligase activity, ZBTB17/MIZ1 operates as a transcription factor to modulate the expression of key importer PEX13, influencing the localization of peroxisomal enzymes. Furthermore, metabolomic profiling reveals that knockdown of ZBTB17 or PEX13 results in similar metabolic alterations, with downregulated purine synthesis. Collectively, we identify ZBTB17 as a key regulator of peroxisomal protein import, thereby affecting peroxisomal function and nucleotide metabolism. Our findings provide insights into the multifaceted regulation of peroxisomes in complex human cells and shed light on the molecular mechanisms underlying ZBTB17's role as a transcriptional regulator.PMID:40243840 | DOI:10.1083/jcb.202407198

Int J Mol Sci. 2025 Mar 27;26(7):3086. doi: 10.3390/ijms26073086.ABSTRACTDeoxynivalenol (DON), one of the most common mycotoxins, is frequently found in foods. This study investigated the effects of orally administered DON on the blood biochemical parameters, growth performance, histology, microbial composition, and metabolism of rats. After a 1-week adaptation period, 4-week-old rats were administered 0.9% saline (control), 1 mg/L DON (T1), 10 mg/L DON (T2), or 50 mg/L DON (T3) by gavage for 49 days. The DON-treated groups had significantly lower body weights than the control group (p < 0.05). Blood alkaline phosphatase, phosphate, cholesterol, amylase, and creatinine levels differed significantly between the DON-treated and control groups (p < 0.05). With increasing DON doses, fibrosis and apoptosis were observed in several tissues. In terms of metabolites, the bile acid biosynthesis pathway emerged as a potential biomarker, while the tryptophan metabolism pathway was found to be the most affected. The fecal microbiota showed significant differences in both alpha and beta diversity between the DON-treated and control groups (p < 0.05). In the cecal and fecal microbiota, the relative abundance of Firmicutes increased in the control and T1 groups, whereas Bacteroidota and Campylobacterota were more abundant in the T2 and T3 groups. In conclusion, our results showed that high DON exposure induces several dose-dependent adverse effects on rats.PMID:40243812 | DOI:10.3390/ijms26073086

Int J Mol Sci. 2025 Mar 27;26(7):3094. doi: 10.3390/ijms26073094.ABSTRACTSpace flight has many adverse effects on the physiological functions of astronauts. Certain similarities have been observed in some physiological processes of rodents and astronauts in space, although there are also differences. These similarities make rodents helpful models for initial investigations into space-induced physiological changes. This study uses a 3D-Clinostat to simulate microgravity and explores the role of microgravity in space flight-induced liver and brain abnormalities by comparing changes in the gut microbiota, serum metabolites, and the function and physiological biochemistry of liver and brain tissues between the simulated microgravity (SMG) group mice and the wild type (WT) group mice. The study, based on hematoxylin-eosin (HE) staining, 16S sequencing technology, and non-targeted metabolomics analysis, shows that the gut tissue morphology of the SMG group mice is abnormal, and the structure of the gut microbiota and the serum metabolite profile are imbalanced. Furthermore, using PICRUST 2 technology, we have predicted the functions of the gut microbiota and serum metabolites, and the results indicate that the liver metabolism and functions (including lipid metabolism, amino acid metabolism, and sugar metabolism, etc.) of the SMG group mice are disrupted, and the brain tissue metabolism and functions (including neurotransmitters and hormone secretion, etc.) are abnormal, suggesting a close relationship between microgravity and liver metabolic dysfunction and brain dysfunction. Additionally, the high similarity in the structure of the gut microbiota and serum metabolite profile between the fecal microbiota transplant (FMT) group mice and the SMG group mice, and the physiological and biochemical differences in liver and brain tissues compared to the WT group mice, suggest that microgravity induces imbalances in the gut microbiota, which in turn triggers abnormalities in liver and brain metabolism and function. Finally, through MetaMapp analysis and Pearson correlation analysis, we found that valeric acid, a metabolite of gut microbiota, is more likely to be the key metabolite that relates to microgravity-induced gut microbiota abnormalities, disorders of amino acid and lipid metabolism, and further induced metabolic or functional disorders in the liver and brain. This study has significant practical application value for deepening the understanding of the adaptability of living organisms in the space environment.PMID:40243802 | DOI:10.3390/ijms26073094

Int J Mol Sci. 2025 Mar 28;26(7):3109. doi: 10.3390/ijms26073109.ABSTRACTKaposi's sarcoma-associated herpesvirus (KSHV) is an oncogenic double-stranded DNA virus. There are no vaccines or antiviral therapies for KSHV. Identifying the cellular metabolic pathways that KSHV manipulates can broaden the knowledge of how these pathways contribute to sustaining lytic infection, which can be targeted in future therapies to prevent viral spread. In this study, we performed an untargeted metabolomic analysis of KSHV infected telomerase-immortalized gingival keratinocytes (TIGK) cells at 4 h post-infection compared to mock-infected cells. We found that the metabolomic landscape of KSHV-infected TIGK differed from that of the mock. Specifically, a total of 804 differential metabolic features were detected in the two groups, with 741 metabolites that were significantly upregulated, and 63 that were significantly downregulated in KSHV-infected TIGK cells. The differential metabolites included ornithine, arginine, putrescine, dimethylarginine, orotate, glutamate, and glutamine, and were associated with pathways, such as the urea cycle, polyamine synthesis, dimethylarginine synthesis, and de novo pyrimidine synthesis. Overall, our untargeted metabolomics analysis revealed that KSHV infection results in marked rapid alterations in the metabolic profile of the oral epithelial cells. We envision that a subset of these rapid metabolic changes might result in altered cellular functions that can promote viral lytic replication and transmission in the oral cavity.PMID:40243754 | DOI:10.3390/ijms26073109

Gut Microbes. 2025 Dec;17(1):2489768. doi: 10.1080/19490976.2025.2489768. Epub 2025 Apr 6.ABSTRACTSevere acute pancreatitis (SAP)-induced intestinal bacterial translocation and enterogenic infection are among the leading causes of mortality in patients. However, the mechanisms by which SAP disrupted the intestinal barrier and led to bacterial translocation remained unclear. Therefore, we employed multi-omics analysis including microbiome, metabolome, epigenome, transcriptome, and mass cytometry (CyTOF) to identify potential targets, followed by functional validation using transgenic mice. The integrated multi-omics analysis primarily indicated overgrowth of intestinal flagellated bacteria, upregulation of intestinal Toll-like receptor 5 (TLR5) and acute inflammatory response, and increased infiltration of intestinal high-expressing TLR5 lamina propria dendritic cells (TLR5hi LPDC) after SAP. Subsequently, intestinal flagellin-TLR5 signaling was activated after SAP. Intestinal barrier disruption, bacterial translocation, and helper T cells (Th) differentiation imbalance caused by SAP were alleviated in TLR5 knocked out (Tlr5-/-) or conditionally knocked out on LPDC (Tlr5ΔDC) mice. However, TLR5 conditional knockout on intestinal epithelial cells (Tlr5ΔIEC) failed to improve SAP-induced bacterial translocation. Moreover, depletion of LPDC and regulatory T cells (Treg) ameliorated bacterial translocation after SAP. Our findings identify TLR5 on LPDC as a potential novel target for preventing or treating intestinal bacterial translocation caused by SAP.PMID:40243695 | DOI:10.1080/19490976.2025.2489768

Int J Mol Sci. 2025 Mar 26;26(7):3043. doi: 10.3390/ijms26073043.ABSTRACTSpatial metabolomics, as a frontier technology, is capable of conducting the comprehensive characterization of metabolites within organisms in terms of qualitative, quantitative and positional dimensions, so as to facilitate the visual analysis of biological processes. This paper summarizes the birth and development of spatial metabolomics, explains its differences and advantages from traditional metabolomics and summarizes its application in plant research. In addition, the limitations of spatial metabolomics are summarized and discussed, along with the technological improvement and application innovation of spatial metabolomics, in order to provide reference for the development strategy of spatial metabolomics and its application in plant research.PMID:40243661 | DOI:10.3390/ijms26073043

Int J Mol Sci. 2025 Mar 25;26(7):2997. doi: 10.3390/ijms26072997.ABSTRACTLiver fibrosis is a pathological manifestation of chronic liver disease developing to the terminal stage, and there is a lack of effective therapeutic drugs in clinical practice. Scutellarin (SCU) is a flavonoid extracted from Erigeron breviscapus (Vaniot.) Hand.-Mazz., which has significant anti-liver-fibrosis efficacy, but its mode of action remains incompletely understood. A liver fibrosis model was built with male Sprague Dawley rats induced with the disease by CCl4 to evaluate the therapeutic effect of drugs. 16S rRNA sequencing and metabolomics were used to analyze the regulatory effects of SCU on intestinal flora and host metabolism; antibiotics were administered to eliminate gut microbiota and fecal microbiota transplantation (FMT) experiments were used to verify the mechanism. The mechanistic basis underlying SCU's hepatic anti-fibrotic effects was screened by network pharmacology combined with transcriptomics, combined with molecular docking, qPCR, and WB verification. The results showed that SCU may play an anti-liver-fibrosis role by correcting the imbalance of gut flora and regulating the linoleic acid and purine metabolic pathways. In addition, SCU can downregulate the levels of proteins and genes related to the PI3K/AKT axis. In summary, SCU alleviates liver fibrosis by reversing intestinal flora imbalance, regulating the metabolic profile, and inhibiting the PI3K/AKT axis.PMID:40243656 | DOI:10.3390/ijms26072997

Int J Mol Sci. 2025 Mar 25;26(7):2992. doi: 10.3390/ijms26072992.ABSTRACTLight is an important environmental regulator of plant secondary metabolism. Terpenoids, the most abundant secondary metabolites in plants, demonstrate a wide spectrum of biologically significant properties, encompassing antimicrobial, antioxidative, and analgesic activities. Litsea cubeba (Lour.) Pers., a core species within the Lauraceae family, exhibits notable pharmacological potential, including antimicrobial and antitumor effects. Here, we found that darkness treatment significantly suppressed terpenoid accumulation in L. cubeba fruits. To clarify the molecular mechanisms underlying the regulatory effect of light and darkness treatments on terpenoid biosynthesis, we conducted a comparative transcriptome profiling of L. cubeba fruits under light and darkness treatments. A total of 13,074 differentially expressed genes (DEGs) were identified among four sampling time points (L1-L2-L3-L4 vs. D1-D2-D3-D4). These genes were enriched in various pathways, with significant enrichment being observed in the terpenoid and other secondary metabolism pathways. Additionally, the enrichment of DEGs in L2 and D2 stages was further studied, and it was found that nine DEGs were significantly enriched in the monoterpene synthesis pathway. The weighted gene co-expression network analysis (WGCNA) showed that alcohol dehydrogenase (ADH), a key enzyme in terpenoid synthesis, had the same expression pattern as WRKY and NAC transcription factors, suggesting their involvement in the biosynthesis of terpenoids in L. cubeba. Expression profiling demonstrated that plastid-localized terpenoid pathway genes were markedly downregulated under darkness treatment. qRT-PCR validation of key genes (LcDXS3, LcHMGS1, LcMDS, and LcTPS19) confirmed the reliability of the transcriptome data, with LcDXS3 exhibiting pronounced declines in expression after 6 h (2.76-fold decrease) and 12 h (2.63-fold decrease) of darkness treatment. These findings provide novel insights into the photoregulatory mechanisms governing terpenoid metabolism in L. cubeba.PMID:40243633 | DOI:10.3390/ijms26072992

Food Funct. 2025 Apr 17. doi: 10.1039/d5fo00656b. Online ahead of print.ABSTRACTDrug-induced liver injury (DILI) is a common adverse drug reaction that can result in liver injury, particularly in cases of paracetamol (APAP) abuse. Schisandra sphenanthera Rehd. et Wils. has attracted attention due to its hepatoprotective properties, and the underlying mechanism is unclear. In this study, a mouse model of APAP-induced liver injury was employed to evaluate network pharmacology analysis, histopathological analysis, the gut microbiota, and fecal metabolome to investigate the mechanism by which S. sphenanthera fruit extract (SFE) alleviates DILI. Network pharmacology indicated that the SFE can attenuate APAP-induced liver injury via key targets, including MAPK3 and CASP3. Furthermore, SFE effectively alleviated APAP-induced oxidative stress (MDA, SOD, and GSH) and inflammation (IL-6, TNF-α, and IL-1β). Further analysis of gut microbiota and fecal metabolites revealed that SFE promoted the growth of Bacteroidales and Erysipelotrichales, and decreased the growth of Lactobacillales, leading to increased production of tryptophan metabolites. Correlation analysis showed that the increase in gut microbiota by SFE was positively correlated with improved antioxidant ability and improved liver and gut function. In conclusion, SFE pretreatment can alleviate APAP-induced liver injury by targeting the gut-liver axis, and provides a valuable reference for the clinical use of SFE in the prevention or treatment of DILI.PMID:40243619 | DOI:10.1039/d5fo00656b