PubMed

BMC Genomics. 2023 Sep 7;24(1):532. doi: 10.1186/s12864-023-09647-0.ABSTRACTSurgical resection remains a critical treatment option for many patients with primary and secondary hepatic neoplasms. Extended hepatectomy (eHx) may be required for some patients with large tumors, which may cause liver failure and death. Partial hepatectomy (pHx) and eHx mouse models were constructed, liver tissues were sampled at 18, 36, and 72 h posthepatectomy. Transcriptome and metabolome analyses were employed to explore the different potential mechanisms in regeneration and injury between pHx and eHx. The results showed that eHx was associated with more severe liver injury and lower survival rates than pHx. Transcriptomics data showed there were 1842, 2129, and 1277 differentially expressed genes (DEGs) in eHx and 962, 1305, and 732 DEGs in pHx at 18, 36, and 72 h posthepatectomy, respectively, compared with the those in the sham groups. Compared with pHx, the number of DEGs in the eHx group reached a maximum of 230 at 18 h after surgery and decreased sequentially to 87 and 43 at 36 and 72 h. Metabolomics analysis identified a total of 1399 metabolites, and 48 significant differentially produced metabolites (DPMs) were screened between eHx and pHx. Combined analysis of DEGs and DPMs indicated that cholesterol metabolism and insulin resistance may be two important pathways for liver regeneration and mouse survival postextended hepatectomy. Our results showed the global influence of pHx and eHx on the transcriptome and metabolome in mouse liver, and revealed cholesterol metabolism and insulin resistance pathways might be involved in regeneration post-pHx and -eHx.PMID:37679685 | DOI:10.1186/s12864-023-09647-0

Nat Metab. 2023 Sep 7. doi: 10.1038/s42255-023-00882-z. Online ahead of print.NO ABSTRACTPMID:37679555 | DOI:10.1038/s42255-023-00882-z

Nat Metab. 2023 Sep 7. doi: 10.1038/s42255-023-00881-0. Online ahead of print.NO ABSTRACTPMID:37679554 | DOI:10.1038/s42255-023-00881-0

Nat Immunol. 2023 Sep 7. doi: 10.1038/s41590-023-01604-z. Online ahead of print.ABSTRACTNeurodegenerative diseases, including Alzheimer's disease (AD), are characterized by innate immune-mediated inflammation, but functional and mechanistic effects of the adaptive immune system remain unclear. Here we identify brain-resident CD8+ T cells that coexpress CXCR6 and PD-1 and are in proximity to plaque-associated microglia in human and mouse AD brains. We also establish that CD8+ T cells restrict AD pathologies, including β-amyloid deposition and cognitive decline. Ligand-receptor interaction analysis identifies CXCL16-CXCR6 intercellular communication between microglia and CD8+ T cells. Further, Cxcr6 deficiency impairs accumulation, tissue residency programming and clonal expansion of brain PD-1+CD8+ T cells. Ablation of Cxcr6 or CD8+ T cells ultimately increases proinflammatory cytokine production from microglia, with CXCR6 orchestrating brain CD8+ T cell-microglia colocalization. Collectively, our study reveals protective roles for brain CD8+ T cells and CXCR6 in mouse AD pathogenesis and highlights that microenvironment-specific, intercellular communication orchestrates tissue homeostasis and protection from neuroinflammation.PMID:37679549 | DOI:10.1038/s41590-023-01604-z

Nat Biotechnol. 2023 Sep 7. doi: 10.1038/s41587-023-01934-1. Online ahead of print.ABSTRACTCharacterization and integration of the genome, epigenome, transcriptome, proteome and metabolome of different datasets is difficult owing to a lack of ground truth. Here we develop and characterize suites of publicly available multi-omics reference materials of matched DNA, RNA, protein and metabolites derived from immortalized cell lines from a family quartet of parents and monozygotic twin daughters. These references provide built-in truth defined by relationships among the family members and the information flow from DNA to RNA to protein. We demonstrate how using a ratio-based profiling approach that scales the absolute feature values of a study sample relative to those of a concurrently measured common reference sample produces reproducible and comparable data suitable for integration across batches, labs, platforms and omics types. Our study identifies reference-free 'absolute' feature quantification as the root cause of irreproducibility in multi-omics measurement and data integration and establishes the advantages of ratio-based multi-omics profiling with common reference materials.PMID:37679543 | DOI:10.1038/s41587-023-01934-1

Sci Data. 2023 Sep 7;10(1):594. doi: 10.1038/s41597-023-02505-4.ABSTRACTChickens are remarkably versatile animals that are used as model organisms for biomedical research. Here, we performed metabolomic and RNA sequencing (RNA-Seq) transcriptomic analyses of the hypothalamus, liver tissue and serum of poultry with different genetic backgrounds, providing detailed information for hypothalamus and liver tissue at the transcriptional level and for liver tissue and serum at the metabolite level. We present two datasets generated from 36 samples from three poultry breeds using high-throughput RNA-Seq and liquid chromatography coupled with mass spectrometry acquisition (LC/MS). The transcriptomic and metabolomic data obtained for poultry of different genetic backgrounds will be a valuable resource for further studies on this model organism.PMID:37679362 | DOI:10.1038/s41597-023-02505-4

Nat Commun. 2023 Sep 7;14(1):5500. doi: 10.1038/s41467-023-40968-6.ABSTRACTAstrocytes contribute to brain inflammation in neurological disorders but the molecular mechanisms controlling astrocyte reactivity and their relationship to neuroinflammatory endpoints are complex and poorly understood. In this study, we assessed the role of the calcium channel, Orai1, for astrocyte reactivity and inflammation-evoked depression behaviors in mice. Transcriptomics and metabolomics analysis indicated that deletion of Orai1 in astrocytes downregulates genes in inflammation and immunity, metabolism, and cell cycle pathways, and reduces cellular metabolites and ATP production. Systemic inflammation by peripheral lipopolysaccharide (LPS) increases hippocampal inflammatory markers in WT but not in astrocyte Orai1 knockout mice. Loss of Orai1 also blunts inflammation-induced astrocyte Ca2+ signaling and inhibitory neurotransmission in the hippocampus. In line with these cellular changes, Orai1 knockout mice showed amelioration of LPS-evoked depression-like behaviors including anhedonia and helplessness. These findings identify Orai1 as an important signaling hub controlling astrocyte reactivity and astrocyte-mediated brain inflammation that is commonly observed in many neurological disorders.PMID:37679321 | DOI:10.1038/s41467-023-40968-6

Signal Transduct Target Ther. 2023 Sep 8;8(1):334. doi: 10.1038/s41392-023-01552-y.ABSTRACTCalorie restriction (CR) or a fasting regimen is considered one of the most potent non-pharmacological interventions to prevent chronic metabolic disorders, ameliorate autoimmune diseases, and attenuate aging. Despite efforts, the mechanisms by which CR improves health, particularly brain health, are still not fully understood. Metabolic homeostasis is vital for brain function, and a detailed metabolome atlas of the brain is essential for understanding the networks connecting different brain regions. Herein, we applied gas chromatography-mass spectrometry-based metabolomics and lipidomics, covering 797 structurally annotated metabolites, to investigate the metabolome of seven brain regions in fasted (3, 6, 12, and 24 h) and ad libitum fed mice. Using multivariate and univariate statistical techniques, we generated a metabolome atlas of mouse brain on the global metabolic signature dynamics across multiple brain regions following short-term fasting (STF). Significant metabolic differences across brain regions along with STF-triggered region-dependent metabolic remodeling were identified. We found that STF elicited triacylglycerol degradation and lipolysis to compensate for energy demand under fasting conditions. Besides, changes in amino acid profiles were observed, which may play crucial roles in the regulation of energy metabolism, neurotransmitter signaling, and anti-inflammatory and antioxidant in response to STF. Additionally, this study reported, for the first time, that STF triggers a significant elevation of N-acylethanolamines, a class of neuroprotective lipids, in the brain and liver. These findings provide novel insights into the molecular basis and mechanisms of CR and offer a comprehensive resource for further investigation.PMID:37679319 | DOI:10.1038/s41392-023-01552-y

Cell Death Dis. 2023 Sep 7;14(9):597. doi: 10.1038/s41419-023-06123-1.ABSTRACTInsulin signaling often plays a role in the regulation of cancer, including tumor initiation, progression, and response to treatment. In addition, the insulin-regulated PI3K-Akt-mTOR pathway plays an important role in the regulation of islet cell proliferation, and this pathway is hyperactivated in human non-functional pancreatic neuroendocrine tumors (PanNETs). We, therefore, investigated the effect of a very low carbohydrate diet (ketogenic diet) on a mouse model that develops non-functional PanNETs to ask how reduced PI3K-Akt-mTOR signaling might affect the development and progression of non-functional PanNET. We found that this dietary intervention resulted in lower PI3K-Akt-mTOR signaling in islet cells and a significant reduction in PanNET formation and progression. We also found that this treatment had a significant effect on the suppression of pituitary NET development. Furthermore, we found that non-functional PanNET patients with lower blood glucose levels tend to have a better prognosis than patients with higher blood glucose levels. This preclinical study shows that a dietary intervention that results in lower serum insulin levels leads to lower insulin signals within the neuroendocrine cells and has a striking suppressive effect on the development and progression of both pancreatic and pituitary NETs.PMID:37679316 | DOI:10.1038/s41419-023-06123-1

Eur Respir J. 2023 Sep 7:2202445. doi: 10.1183/13993003.02445-2022. Online ahead of print.ABSTRACTRATIONALE: Pulmonary vascular disease (PVD) affects the majority of preterm neonates with bronchopulmonary dysplasia (BPD) and significantly determines long-term mortality through undetected progression into pulmonary hypertension.OBJECTIVES: To associate characteristics of pulmonary artery (PA) flow and cardiac function with BPD-associated PVD near term using advanced magnetic resonance imaging (MRI) for improved risk stratification.METHODS: Preterms <32 weeks postmenstrual age (PMA) with/without BPD were clinically monitored including standard echocardiography and prospectively enrolled for 3TMRI in spontaneous sleep near term (AIRR study). Semi-manual PA flow quantification (phase-contrast MRI, no BPD n=28, mild n=35, moderate/severe n=25) was complemented by cardiac function assessment (cine MRI).MEASUREMENTS AND MAIN RESULTS: We identified abnormalities in PA flow and cardiac function, i.e. increased net forward volume (ratio right-over-left), decreased mean relative area change and pathologic right end-diastolic volume to sensitively detect BPD-associated PVD while correcting for PMA (L1OAUC=0.88/sensitivity=0.80/specificity=0.81). We linked these changes to increased right ventricular (RV) afterload (RV-arterial coupling (p=0.02), PA midsystolic notching (p=0.015(t2)), cardiac index (p=1.67×10-8)) and correlated echocardiographic findings. Identified in moderate/severe BPD, we successfully applied the PA flow model in heterogeneous mild BPD cases, demonstrating strong correlation of PVD probability with indicators of BPD severity, i.e., duration of mechanical ventilation (R=0.62, p=3.7×10-4) and oxygen supplementation (R=0.58, p=9.2×10-4).CONCLUSIONS: Abnormalities in MRI PA flow and cardiac function exhibit significant, synergistic potential to detect BPD-associated PVD, advancing the possibilities of risk-adapted monitoring.PMID:37678954 | DOI:10.1183/13993003.02445-2022

Life Sci. 2023 Sep 5:122073. doi: 10.1016/j.lfs.2023.122073. Online ahead of print.ABSTRACTAIMS: Primary choledocholithiasis is a common digestive disease with high morbidity and relapse. However, the compositions and functions of the bile microbial ecosystem and the pathogenesis of microfloral regulation of host metabolism resulting in stone formation are poorly understood.MAIN METHODS: Biliary samples collected from patients with acute cholangitis induced by benign biliary stricture (nonlithiasis group, n = 17) and primary choledocholithiasis (lithiasis group, n = 33) were subjected to multiomics analyses. Furthermore, clinicopathological features collected over a 24-month follow-up period were examined to evaluate the predictive value of candidate microbes.KEY FINDINGS: Five alpha diversity indices of the bile microbiome were significantly decreased in the lithiasis group. Furthermore, we identified 49 differential bile flora between the two groups, and the relative abundances of 6 bacteria, Actinobacteria, Actinobacteriota, Staphylococcales, Micrococcales, Altererythrobacter and Carnobacteriaceae, were associated with primary choledocholithiasis relapse conditions. Multiomics analyses showed that specific changes in disease-related bacterial taxa were closely related to metabolite variation (low-molecular weight carboxylic acids, sterol liquid and acylcarnitine), which might reflect disease prognosis. According to microbiomic and metabolomic pathway analyses, we revealed that bacterial infections, microbiota-derived amino acid metabolites and secondary bile acid-related pathways were significantly enriched in the stone-formation group, suggesting a novel host-microbial metabolic mechanism of primary choledocholithiasis.SIGNIFICANCE: Our study first indicates bile host-microbial dysbiosis modulates the abnormal accumulation of metabolites might further disrupt calcium homeostasis and generate insoluble saponification. Additionally, we determined the predictive value of Actinomycetes phylum reduction for recurrence in primary common bile duct stone patients.PMID:37678747 | DOI:10.1016/j.lfs.2023.122073

Am J Kidney Dis. 2023 Sep 5:S0272-6386(23)00781-3. doi: 10.1053/j.ajkd.2023.05.014. Online ahead of print.ABSTRACTRATIONALE & OBJECTIVE: Chronic kidney disease (CKD) leads to lipid and metabolic abnormalities, but a comprehensive investigation of lipids, lipoprotein particles, and circulating metabolites associated with the risk of CKD is lacking. We examined the associations of nuclear magnetic resonance (NMR)-based metabolomics data with CKD risk in the UK Biobank study.STUDY DESIGN: Observational cohort study.SETTING: & Participants: A total of 91,532 participants in the UK Biobank Study without CKD and not receiving lipid-lowering therapy.EXPOSURES: Levels of metabolites including lipid concentration and composition within 14 lipoprotein subclasses, as well as other metabolic biomarkers, were quantified via NMR spectroscopy.OUTCOMES: Incident CKD identified using ICD codes in any primary care data, hospital admission records, or death register records.ANALYTICAL APPROACH: Cox proportional hazards regression models were used to estimate hazard ratios and 95% confidence intervals.RESULTS: We identified 2269 CKD cases over a median follow-up of 13.1 years via linkage with the electronic health records. After adjusting for covariates and correcting for multiple testing, 90 of 142 biomarkers were significantly associated with incident CKD. In general, higher concentrations of very-low-density lipoprotein (VLDL) particles were associated with a higher risk of CKD whereas higher concentrations of high-density lipoprotein (HDL) particles were associated with a lower risk of CKD. Higher concentrations of cholesterol, phospholipids, and total lipids within VLDL were associated with a higher risk of CKD, whereas within HDL, they were associated with a lower risk of CKD. Further, higher triglyceride levels within all lipoprotein subclasses, including all HDL particles were associated with greater risk of CKD. We also identified that several amino acids, fatty acids and inflammatory biomarkers were associated with risk of CKD.LIMITATIONS: Potential underreporting of CKD cases because of case identification via electronic health records.CONCLUSIONS: Our findings highlight multiple known and novel pathways linking circulating metabolites to the risk of CKD.PMID:37678743 | DOI:10.1053/j.ajkd.2023.05.014

Adv Nutr. 2023 Sep 5:S2161-8313(23)01365-0. doi: 10.1016/j.advnut.2023.09.002. Online ahead of print.ABSTRACTCarotenoids have been associated with risk reduction for several chronic diseases, including the association of their dietary intake/circulating levels with reduced incidence of obesity, type 2 diabetes, certain types of cancer, and even lower total mortality. In addition to some carotenoids constituting vitamin A precursors, they are implicated in potential antioxidant effects and pathways related to inflammation and oxidative stress, including transcription factors such as nuclear factor kappa B (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2). Carotenoids and metabolites may also interact with nuclear receptors, mainly retinoic acid receptor/retinoid X receptor (RAR/RXR) and peroxisome proliferator-activated receptors (PPARs) that play a role in the immune system and cellular differentiation. Therefore, a large number of downstream targets are likely influenced by carotenoids, including but not limited to genes, proteins implicated in oxidative stress and inflammation, antioxidant enzymes and cellular differentiation processes. Furthermore, recent studies also propose an association between carotenoid intake and gut microbiota. While all these endpoints could be individually assessed, a more complete/integrative way to determine a multitude of health-related aspects of carotenoids includes (multi)-omics-related techniques, especially transcriptomics, proteomics, lipidomics and metabolomics, but also metagenomics, measured in a variety of biospecimens including plasma, urine, stool, white blood cells or other tissue cellular extracts. In this review, we highlight the use of -omics technologies to assess health-related effects of carotenoids in mammalian organisms and models.PMID:37678712 | DOI:10.1016/j.advnut.2023.09.002

Metab Eng. 2023 Sep 5:S1096-7176(23)00122-2. doi: 10.1016/j.ymben.2023.09.002. Online ahead of print.ABSTRACTThe capability of cyanobacteria to produce sucrose from CO2 and light has a remarkable societal and biotechnological impact since sucrose can serve as a carbon and energy source for a variety of heterotrophic organisms and can be converted into value-added products. However, most metabolic engineering efforts have focused on understanding local pathway alterations that drive sucrose biosynthesis and secretion in cyanobacteria rather than analyzing the global flux re-routing that occurs following induction of sucrose production by salt stress. Here, we investigated global metabolic flux alterations in a sucrose-secreting (cscB-overexpressing) strain relative to its wild-type Synechococcus elongatus 7942 parental strain. We used targeted metabolomics, 13C metabolic flux analysis (MFA), and genome-scale modeling (GSM) as complementary approaches to elucidate differences in cellular resource allocation by quantifying metabolic profiles of three cyanobacterial cultures - wild-type S. elongatus 7942 without salt stress (WT), wild-type with salt stress (WT/NaCl), and the cscB-overexpressing strain with salt stress (cscB/NaCl) - all under photoautotrophic conditions. We quantified the substantial rewiring of metabolic fluxes in WT/NaCl and cscB/NaCl cultures relative to WT and identified a metabolic bottleneck limiting carbon fixation and sucrose biosynthesis. This bottleneck was subsequently mitigated through heterologous overexpression of glyceraldehyde-3-phosphate dehydrogenase in an engineered sucrose-secreting strain. Our study also demonstrates that combining 13C-MFA and GSM is a useful strategy to both extend the coverage of MFA beyond central metabolism and to improve the accuracy of flux predictions provided by GSM.PMID:37678664 | DOI:10.1016/j.ymben.2023.09.002

Bioresour Technol. 2023 Sep 5:129718. doi: 10.1016/j.biortech.2023.129718. Online ahead of print.NO ABSTRACTPMID:37678649 | DOI:10.1016/j.biortech.2023.129718

Sci Total Environ. 2023 Sep 5:166886. doi: 10.1016/j.scitotenv.2023.166886. Online ahead of print.ABSTRACTPolycyclic aromatic hydrocarbons (PAHs) and Chlorinated PAHs (Cl-PAHs) are ubiquitous environmental contaminants. The toxicological information of anthracene (Ant) and its chlorinated derivatives is quite limited. In this study, an integrated metabolomic and transcriptomic analysis approach was adopted to assess the toxic effects triggered by Ant and its chlorinated derivatives, 2-chloroanthracene (2-ClAnt) and 9,10-dichloroanthracen (9,10-Cl2Ant), at human-relevant levels on human normal hepatocyte L02 cells. The cell viability test showed no significant effects on the viability of L02 cells exposed to Ant, 2-ClAnt and 9,10-Cl2Ant at doses of 5-500 nM for 24 h. However, based on transcriptomic analysis, Ant, 2-ClAnt and 9,10-Cl2Ant exposure at human-relevant levels obviously perturbed global gene expression in L02 cells and induced the differential expression of several genes related to cancer development. As the number of genes related to cancer development altered by 9,10-Cl2Ant is the largest, 9,10-Cl2Ant posed greater risks of tumor development than Ant and 2-ClAnt did. Metabolomics analysis demonstrated that Ant, 2-ClAnt and 9,10-Cl2Ant caused significant metabolic perturbation in L02 cells. Pathway enrichment analysis indicated that Ant, 2-ClAnt and 9,10-Cl2Ant mainly perturbed the lipid metabolism and nucleotide metabolism pathway. However, 9,10-Cl2Ant caused a wider perturbation to metabolic pathways than Ant and 2-ClAnt did. In addition, dysregulation of nucleotide metabolism perturbed by Ant, 2-ClAnt and 9,10-Cl2Ant may be associated with the genomic instability and further carcinogenesis.PMID:37678537 | DOI:10.1016/j.scitotenv.2023.166886

Sci Total Environ. 2023 Sep 5:166885. doi: 10.1016/j.scitotenv.2023.166885. Online ahead of print.ABSTRACTThe risks of Zinc oxide nanoparticles (ZnO NPs) applications in biological medicine, food processing industry, agricultural production and the biotoxicity brought by environmental invasion of ZnO NPs both gradually troubled the public due to the lack of research on detoxification strategies. TFEB-regulated autophagy-pyroptosis pathways were found as the crux of the hepatotoxicity induced by ZnO NPs in our latest study. Here, our study served as a connecting link between preceding toxic target and the following protection mechanism of Paeoniflorin (PF). According to a combined analysis of network pharmacology/molecular docking-intestinal microbiota-metabolomics first developed in our study, PF alleviated the hepatotoxicity of ZnO NPs from multiple aspects. The hepatic inflammatory injury and hepatocyte pyroptosis in mice liver exposed to ZnO NPs was significantly inhibited by PF. And the intestinal microbiota disorder and liver metabolic disturbance were rescued. The targets predicted by bioinformatics and the signal trend in subacute toxicological model exhibited the protectiveness of PF related to the SIRT1-mTOR-TFEB pathway. These evidences clarified multiple protective mechanisms of PF which provided a novel detoxification approach against ZnO NPs, and further provided a strategy for the medicinal value development of PF.PMID:37678520 | DOI:10.1016/j.scitotenv.2023.166885

Food Chem. 2023 Aug 26;433:137302. doi: 10.1016/j.foodchem.2023.137302. Online ahead of print.ABSTRACTIn the current context of developing aromatic beers, our study aims at deciphering the chemical characterisation of cones from 39 wild hop genotypes collected in the North of France and replanted in an experimental hop farm, as well as 10 commercial and 3 heirloom varieties, using HS-SPME/GC-MS for the volatile compounds, UHPLC-UV for phenolic compound quantification, and UHPLC-IMS-HRMS for untargeted metabolomics. These analyses revealed a strong opposition between wild accessions and reference varieties, and an original chemical composition of some genotypes. 27 beers were produced with the same recipe, analysed by SBSE-GC-MS and evaluated by panellists. The unique difference relates to the hops to be assessed in order to determine their sensory profile. The different datasets were compared by OPLS-DA analysis in order to identify chemical markers which may influence the hop aromatic potential. Our results highlight the aromatic potential of some wild accessions, close to the commercial variety Cascade.PMID:37678125 | DOI:10.1016/j.foodchem.2023.137302

Biomed Pharmacother. 2023 Sep 5;166:115434. doi: 10.1016/j.biopha.2023.115434. Online ahead of print.ABSTRACTRenal interstitial fibrosis (RIF), a progressive process affecting the kidneys in chronic kidney disease (CKD), currently lacks an effective therapeutic intervention. Traditional Chinese medicine (TCM) has shown promise in reducing RIF and slowing CKD progression. In this study, we demonstrated the dose-dependent attenuation of RIF by Ootheca mantidis (SPX), a commonly prescribed TCM for CKD, in a mouse model of unilateral ureteral obstruction (UUO). RNA-sequencing analysis suggested that SPX treatment prominently downregulated apoptosis and inflammation-associated pathways, thereby inhibiting the fibrogenic signaling in the kidney. We further found that transplantation of fecal microbiota from SPX-treated mice conferred protection against renal injury and fibrosis through suppressing apoptosis in UUO mice, indicating that SPX ameliorated RIF via remodeling the gut microbiota and reducing apoptosis in the kidneys. Further functional exploration of the gut microbiota combined with fecal metabolomics revealed increased levels of some probiotics, including Akkermansia muciniphila (A. muciniphila), and modulations in glutamine-related amino acid metabolism in UUO mice treated with SPX. Subsequent colonization of A. muciniphila and supplementation with glutamine effectively mitigated cell apoptosis and RIF in UUO mice. Collectively, these findings unveil a functionally A. muciniphila- and glutamine-involved gut-renal axis that contributes to the action of SPX, and provide important clue for the therapeutic potential of SPX, A. muciniphila, and glutamine in combatting RIF.PMID:37677965 | DOI:10.1016/j.biopha.2023.115434

J Pharm Biomed Anal. 2023 Aug 29;236:115689. doi: 10.1016/j.jpba.2023.115689. Online ahead of print.ABSTRACTHedysari Radix Praeparata Cum Melle (HRPCM) and Astragali Radix Praeparata Cum Melle (ARPCM) are capable of improving spleen-qi deficiency (SQD) syndrome especially in the gastrointestinal dysfunction and decreased immunity in traditional Chinese medicine clinically. This study aims to compare and reveal the metabolic differences between HRPCM and ARPCM for SQD rats. Firstly, HRPCM (12.6 g/kg) and ARPCM (12.6 g/kg) were used to intervene SQD rats to further evaluate the effect. The results showed that HRPCM and ARPCM were able to improve the spleen pathology, increase the body weight, the rectal temperature, the spleen index, the thymus index, the levels of GAS and D-xylose in serum, and decrease the levels of IL-2, IL-6 and TNF-α in serum for SQD rats. Then, the studies of metabolic differences in serum and spleen were carried out using UPLC-Q-TOF-MS. The findings emphasized that HRPCM and ARPCM not only regulated metabolic profiling of serum and spleen in SQD rats, but also existed differences. HRPCM and ARPCM regulated metabolic pathways mainly including lipid metabolism, energy metabolism, amino acid metabolism, nucleotide metabolism, sugar metabolism and other types of metabolism for SQD rats. However, the metabolite profiles in SQD rats changed significantly, mainly involving abnormal glycine synthesis occurred in SQD rats. The expression trends of metabolites in HRPCM and ARPCM intervention for SQD rats were partly the same. Interestingly, there are similarities and differences in metabolic profiling between HRPCM and ARPCM for SQD rats. The differences were mainly in the synthesis of L-glutamine in amino acid metabolism.PMID:37677887 | DOI:10.1016/j.jpba.2023.115689