Metabolites最新文献

{"title":"Impact of Heavy Metals on the Antioxidant Activity of Vitamin D: A Metabolic Perspective.","authors":"Ji Seo Park, Mi-Ri Gwon, Jae Hwa Lee, Jin Ju Park, Hae Won Lee, Duk-Hee Lee, Sook Jin Seong, Young-Ran Yoon","doi":"10.3390/metabo15070440","DOIUrl":"https://doi.org/10.3390/metabo15070440","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Vitamin D (VD) is metabolized in the body and plays a crucial role in regulating the antioxidant system. While exposure to heavy metals (HMs) inhibits VD activity, HMs can also be absorbed following VD stimulation. Despite differing views on the interaction between HM and VD activity, the effects of HM exposure on VD-related pathways have not been examined using metabolomics. This study aimed to investigate the impact of HM exposure on VD-related antioxidant activity under VD deficiency conditions using untargeted metabolic profiling. <b>Methods</b>: In this retrospective cohort study, 46 plasma samples were analyzed using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS). Metabolic profiling was performed on two groups: individuals with severe VD deficiency and low HM exposure (SVDD-LHM) and those with VD deficiency and high HM exposure (VDD-HHM). <b>Results</b>: As a compensatory response to oxidative stress induced by HMs, VD-related antioxidant pathways may be associated with elevated levels of antioxidants, including bilirubin, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). In-creases in EPA and DHA were also linked to alterations in lipid metabolism, including diacylglycerol and phosphatidylcholine levels. DHA showed an area under the curve (AUC) of 0.850 (95% CI: 0.651-0.990), suggesting that DHA could serve as a potential biomarker for VD activity in response to HM exposure. <b>Conclusions</b>: The identified metabolites and metabolic pathways suggest that HM exposure may stimulate VD-related antioxidant activity, even under VD-deficient conditions.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Angiotensin-Converting Enzyme Inhibitory Activity of Selected Phenolic Acids, Flavonoids, Their <i>O</i>-Glucosides, and Low-Molecular-Weight Phenolic Metabolites in Relation to Their Oxidation Potentials.","authors":"Danuta Zielińska, Małgorzata Starowicz, Małgorzata Wronkowska, Henryk Zieliński","doi":"10.3390/metabo15070443","DOIUrl":"https://doi.org/10.3390/metabo15070443","url":null,"abstract":"<p><p><b>Background/Objectives</b>: In this study, the angiotensin-converting enzyme (ACE) inhibitory activity of selected phenolic acids, flavonoids, their <i>O</i>-glucosides, and low-molecular-weight phenolic metabolites was addressed to show their importance against blood hypertension. <b>Methods</b>: A fluorescence assay was used for the determination of the ACE inhibitory activity, whereas the first anodic peak oxidation potential (Epa) was provided by the differential pulse voltammetry (DPV) method. The relationship between the ACE inhibitory activity and Epa was evaluated. <b>Results</b>: Phenolic acids showed a very low ACE inhibitory activity, and their rank was chlorogenic acid > p-coumaric acid > sinapic acid > gentisic acid > ferulic acid > syringic acid > vanillic acid > protocatechuic acid > caffeic acid. The low-molecular-weight phenolic metabolites of flavonoids showed a moderate ACE inhibitory activity. In contrast, flavonoid aglicones had the highest ACE inhibitory activity, and the order was luteolin > quercetin > kaempferol > cyanidin > delphinidin > pelargonin > naringenin. A lower inhibition activity was noted for quercetin-3-<i>O</i>-glucoside, luteolin-4'-<i>O</i>-glucosides, cyanidin-3-<i>O</i>-glucoside, and pelargonidin-3-<i>O</i>-glucosides, whereas a higher ACE inhibition activity was observed for 7-<i>O</i>-glucosides of luteolin, apigenin, and kaempferol. A lack of correlation was found between the IC₅₀ of phenolic acids, low-molecular-weight phenolic metabolites, and their Epa values. In contrast, weak positive correlations were found between the IC₅₀ of aglicons, 3-<i>O</i>-glucosides, 7-<i>O</i>-glucosides, and their Epa values provided by the DPV (r = 0.61, r = 0.66 and r = 0.88, respectively). <b>Conclusions</b>: This study expands our knowledge of the ACE inhibitory activity of phenolic compounds.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"(-)-Epigallocatechin-3-Gallate Suppresses Hyperexcitability in Rat Primary Nociceptive Neurons Innervating Inflamed Tissues: A Comparison with Lidocaine.","authors":"Syogo Utugi, Yukito Sashide, Mamoru Takeda","doi":"10.3390/metabo15070439","DOIUrl":"https://doi.org/10.3390/metabo15070439","url":null,"abstract":"<p><p><b>Objective:</b> Given the side effects and reduced efficacy of conventional local anesthetics in inflammatory conditions, there is a compelling need for complementary alternative medicine (CAM), particularly those based on phytochemicals. While a previous study showed that in vivo local injection of (-)-epigallocatechin-3-gallate (EGCG) into the peripheral receptive field suppresses the excitability of rat trigeminal ganglion (TG) neurons in the absence of inflammation, the acute effects of EGCG in vivo, especially on TG neurons under inflammatory conditions, are still unknown. We aimed to determine if acute local EGCG administration into inflamed tissue effectively attenuates the excitability of nociceptive TG neurons evoked by mechanical stimulation. <b>Methods:</b> The escape reflex threshold was measured to assess hyperalgesia caused by complete Freund's adjuvant (CFA)-induced inflammation. To assess neuronal activity, extracellular single-unit recordings were performed on TG neurons in anesthetized CFA-inflamed rats in response to orofacial mechanical stimulation. <b>Results:</b> The mechanical escape threshold was significantly lower in CFA-inflamed rats compared to before CFA injection. EGCG (1-10 mM) reversibly and dose-dependently inhibited the mean firing frequency of TG neurons evoked by both non-noxious and noxious mechanical stimuli (<i>p</i> < 0.05). For comparison, 1% lidocaine (37 mM), a local anesthetic, also caused reversible inhibition of the mean firing frequency in inflamed TG neurons responding to mechanical stimuli. Importantly, 10 mM EGCG produced a significantly greater magnitude of inhibition on TG neuronal discharge frequency than 1% lidocaine (noxious, lidocaine vs. EGCG, 19.7 ± 3.3% vs. 42.3 ± 3.4%, <i>p</i> < 0.05). <b>Conclusions:</b> Local injection of EGCG into inflamed tissue effectively suppresses the excitability of nociceptive primary sensory TG neurons, as indicated by these findings. Significantly, locally administered EGCG exerted a more potent local analgesic action compared to conventional voltage-gated sodium channel blockers. This heightened efficacy originates from EGCG's ability to inhibit both generator potentials and action potentials directly at nociceptive primary nerve terminals. As a result, EGCG stands out as a compelling candidate for novel analgesic development, holding particular relevance for CAM strategies.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association Between Habitual Dietary Intake and Urinary Metabolites in Adults-Results of a Population-Based Study.","authors":"Annika Blümlhuber, Dennis Freuer, Nina Wawro, Florian Rohm, Christine Meisinger, Jakob Linseisen","doi":"10.3390/metabo15070441","DOIUrl":"https://doi.org/10.3390/metabo15070441","url":null,"abstract":"<p><strong>Background: </strong>Chronic non-communicable diseases (NCDs) are a major global health challenge, with unhealthy diets contributing significantly to their burden. Metabolomics data offer new possibilities for identifying nutritional biomarkers, as demonstrated in short-term intervention studies. This study investigated associations between habitual dietary intake and urinary metabolites, a not well-studied area.</p><p><strong>Methods: </strong>Data were available from 496 participants of the population-based MEIA study. Linear and median regression models examined associations between habitual dietary intake and metabolites, adjusted for possible confounders. K-means clustering identified urinary metabolite clusters, and multinomial regression models were applied to analyze associations between food intake and metabolite clusters.</p><p><strong>Results: </strong>Using linear regression models, previously reported associations could be replicated, including citrus intake with proline betaine, protein intake with urea, and fiber intake with hippurate. Novel findings include positive associations of poultry intake with taurine, indoxyl sulfate, 1-methylnicotinamide, and trimethylamine-N-oxide. Milk substitutes were positively associated with urinary uracil, pseudouridine, 4-hydroxyhippurate, and 3-hydroxyhippurate, and inversely associated with quinic acid. Dietary fiber intake showed a positive association with 3-(3-hydroxyphenyl)-3-hydroxypropionic acid and a negative association with indoxyl sulfate. We identified sucrose and taurine as key metabolites differentiating metabolite clusters. Multinomial regression analysis confirmed significantly different dietary associations across clusters, particularly for fruits, processed meat, poultry, and alcoholic beverages.</p><p><strong>Conclusions: </strong>This study highlights established and novel food-metabolite associations, demonstrating the potential of urinary metabolomics for use as nutritional biomarkers in individuals from the general population.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Imprint Desorption Electrospray Ionization Mass Spectrometry Imaging (IDESI-MSI) Reveals Absorption of Triclopyr-Based Herbicide in Plants and Mouse Organs.","authors":"Hanzhi Liu, Yunshuo Tian, Ruolun Wei, Yifan Meng, Richard N Zare","doi":"10.3390/metabo15070437","DOIUrl":"https://doi.org/10.3390/metabo15070437","url":null,"abstract":"<p><strong>Background: </strong>Understanding the absorption and distribution of herbicides in plants and animal tissues is essential for assessing their potential risks to human health.</p><p><strong>Method: </strong>In this study, we employed imprint desorption electrospray ionization mass spectrometry imaging (IDESI-MSI) to visualize in both vegetable and animal tissues the absorption of Roundup which is a widely used herbicide.</p><p><strong>Results: </strong>Using IDESI-MSI with a pixel size of 150 µm, we detected the herbicide alongside several endogenous metabolites on oil-absorbing films applied to carrot sections. Time-course experiments revealed progressive herbicide penetration into carrot tissue, with penetration depth increasing linearly over time at a rate of approximately 0.25 mm/h. In contrast, green pepper samples showed minimal herbicide infiltration, likely owing to their hydrophobic cuticle barrier. Additionally, mice fed with herbicide-treated carrots exhibited detectable levels of herbicide in liver and kidney tissues.</p><p><strong>Conclusions: </strong>These findings highlight the utility of IDESI-MSI as a powerful analytical platform for the rapid evaluation of chemical migration and absorption in food and biological systems, with important implications for food safety and toxicological research.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nutri-Epigenetic Regulation of Vitamin D-Impact on Metabolism and Biological Functions: Narrative Review.","authors":"Magdalena Kowalówka, Ilona Górna, Marta Karaźniewicz-Łada, Dominika Kusyk, Juliusz Przysławski, Sławomira Drzymała-Czyż","doi":"10.3390/metabo15070436","DOIUrl":"https://doi.org/10.3390/metabo15070436","url":null,"abstract":"<p><p>Vitamin D deficiency is widespread. It increases the risk of several diseases. Therefore, researchers have long studied the factors that influence vitamin D levels in the body. These include its metabolism, catabolism, transport and binding of vitamin D to the receptor VDR. Currently, an increasing number of studies are focusing on genetic factors. Variations in vitamin D levels, including vitamin D deficiency, are under substantial genetic control. There is a reciprocity between the vitamin D system and epigenetic mechanisms. Vitamin D metabolism, on the one hand, is regulated by epigenetic mechanisms and, on the other hand, is involved in regulating epigenetic events. To appraise recent advances in nutrigenomics with its application in public health, several databases, including PubMed, Scopus and Web of Science, were investigated in detail. Nutri-epigenetics deals with the interplay between dietary components and the possible resulting changes in the epigenome. There is, therefore, great potential for the development of nutri-epigenetics. The purpose of the narrative review is to highlight the genetic aspects of vitamin D, its receptor VDR and vitamin D-related gene polymorphisms with a particular focus on vitamin D gene regulation. Particular attention is paid to the vitamin D response index.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of Processing Impact on Raspberries Based on Broad-Spectrum Metabolomics.","authors":"Xiaoge Wang, Qiyuan Liao, Fan Wang, Xuelin Rui, Yushan Liu, Rui Wang","doi":"10.3390/metabo15070435","DOIUrl":"https://doi.org/10.3390/metabo15070435","url":null,"abstract":"<p><p><b>Objective:</b> Our objective was to explore the regulatory mechanism of salt processing on the metabolome of the raspberry and its potential efficacy against diabetic nephropathy (DN), providing metabolomic and network pharmacological evidence for the scientific connotation of traditional Chinese medicine processing. <b>Methods:</b> Ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS)-based metabolomics was used to compare the metabolic profiles between raw and salt-processed raspberries. Network pharmacology was applied to screen the common targets of the active components in the salt-processed raspberry and DN-related pathways, followed by in vitro cell experiments to validate the regulation of the MAPK signaling pathway. <b>Results:</b> The metabolomic analysis identified 80 differentially expressed metabolites, among which 13 key components (VIP ≥ 1, FC ≥ 2) were significantly altered, including enriched flavonoids (e.g., luteolin-7-O-glucoside), triterpenoid saponins (Raspberryides H/F), and phenolic acids (ellagic acid). The network pharmacology revealed that the salt-processed raspberries regulated the DN-related pathways through 122 common targets, with the core nodes focusing on the signaling molecules (e.g., AKT1, EGFR) involved in the MAPK signaling pathway and apoptosis regulation. The in vitro experiments confirmed that the salt-processed raspberry extract (160-640 μg/mL) significantly inhibited the phosphorylation levels of p38/ERK/JNK in high-glucose-induced renal cells. <b>Conclusions:</b> This study firstly combines metabolomics and network pharmacology to reveal the regulatory mechanism of salt processing on the active components of raspberries. The salt-processing technology enhanced the inhibitory effect of raspberries on the MAPK signaling pathway, thereby ameliorating the progression of DN. These findings provide scientific support for establishing a metabolomics-based quality control system for traditional Chinese medicine processing. The current findings are primarily based on in vitro models, and in vivo validation using DN animal models is essential to confirm the therapeutic efficacy and safety of salt-processed raspberries.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolomic Alterations in Patients with Obesity and the Impact of Metabolic Bariatric Surgery: Insights for Future Research.","authors":"Ioanna A Anastasiou, Dimitris Kounatidis, Miikka-Juhani Honka, Natalia G Vallianou, Eleni Rebelos, Nikolaos Nektarios Karamanolis, Maria Dalamaga, Constantinos Pantos, Iordanis Mourouzis","doi":"10.3390/metabo15070434","DOIUrl":"https://doi.org/10.3390/metabo15070434","url":null,"abstract":"<p><p>Metabolomics has emerged as a vital tool for understanding the body's responses to therapeutic interventions. Metabolic bariatric surgery (MBS) is widely recognized as the most effective treatment modality for severe obesity and its associated comorbidities. This review seeks to analyze the current evidence on the metabolomic profiles of patients with obesity and the impact of various bariatric surgical procedures, with the objective of predicting clinical outcomes, including weight loss and remission of type 2 diabetes (T2D). The data gathered from original studies examining metabolomic changes following MBS have been meticulously compiled and summarized. The findings revealed significant alterations in metabolites across various classes, including amino acids, lipids, energy-related compounds, and substances derived from the gut microbiota. Notably, elevated preoperative levels of specific lipids, such as phospholipids, long-chain fatty acids, and bile acids, were correlated with postoperative remission of T2D. In conclusion, metabolite profiling holds great promise for predicting long-term responses to different bariatric surgery procedures. This innovative approach has the potential to facilitate personalized treatment strategies and optimize the allocation of healthcare resources.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Excessive Iron Induces Macrophage Dysfunction in the Liver, Causing Adverse Pregnancy Outcomes in Mice.","authors":"Sayaka Shimazaki, Ren Ozawa, Akari Isobe, Sohei Kuribayashi, Hisataka Iwata, Koumei Shirasuna","doi":"10.3390/metabo15070431","DOIUrl":"https://doi.org/10.3390/metabo15070431","url":null,"abstract":"<p><strong>Background: </strong>Iron is an important micronutrient under physiological conditions, including pregnancy. On the other hand, excessive iron intake is also associated with adverse pregnancy outcomes. Macrophages are crucial in regulating iron homeostasis and pregnancy conditions. However, the role of macrophages in iron metabolism during pregnancy is unclear. Therefore, we used mouse models to investigate whether maternal iron overload induces pregnancy complications and their interactions with macrophages.</p><p><strong>Methods and results: </strong>Administration of high-dose iron (iron dextran) by intraperitoneal injection to pregnant mice induced pregnancy complications such as fetal death, but low-dose iron did not affect fetal weight. In the placenta, the amount of iron was significantly increased and levels of macrophages were decreased by iron administration. In the liver, iron administration dramatically increased the amount of iron, with increased inflammatory cytokines tumor necrosis factor-α (TNFα) and interleukin-6. Macrophages were observed to surround deposited iron in the liver. In an in vitro experiment, treatment with iron stimulated TNFα secretion with cell death in macrophages, but not in liver cells. To investigate the importance of macrophages during pregnancy, clodronate liposomes were administered to reduce macrophages in pregnant mice. The macrophage reduction in pregnant mice resulted in an increased absorption rate and fetal growth restriction, together with higher iron accumulation and inflammatory cytokines in the liver.</p><p><strong>Conclusions: </strong>Maternal excess iron may induce inflammatory conditions with macrophage dysfunction in the liver, resulting in pregnancy complications. The reduction in macrophages also induced higher iron levels and adverse effects during pregnancy, suggesting a vicious cycle between excessive iron and macrophage dysfunction during pregnancy.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integration of Pseudotargeted Metabolomics and Microbiomics Reveals That Hugan Tablets Ameliorate NASH with Liver Fibrosis in Mice by Modulating Bile Acid Metabolism via the Gut Microbiome.","authors":"Wenran Dong, Ying Wang, Huajinzi Li, Huilin Ma, Yingxi Gong, Gan Luo, Xiaoyan Gao","doi":"10.3390/metabo15070433","DOIUrl":"https://doi.org/10.3390/metabo15070433","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Non-alcoholic steatohepatitis (NASH) carries a high risk of developing hepatic fibrosis. Hugan tablets (HGTs), a traditional Chinese medicine, have exhibited potent anti-hepatic fibrosis effects, though the underlying mechanisms remain unclarified. This study aims to assess the efficacy of HGTs against NASH-related liver fibrosis in mice and investigate the underlying mechanisms via the integration of pseudotargeted metabolomics and microbiomics. <b>Methods</b>: C57BL/6 mice were fed a choline-deficient, ethionine-supplemented (CDE) diet and treated with HGTs. The therapeutic effects of HGTs in CDE mice were assessed. The underlying mechanism of HGTs was investigated by the integration of microbiomics, a pseudo-sterile model, untargeted followed by pseudotargeted metabolomics, and molecular docking. <b>Results</b>: HGTs alleviated NASH-related hepatic fibrosis in CDE mice and restored the composition of the gut microbiota. The depletion of the gut microbiota eliminated the anti-hepatic fibrosis effect of HGTs. HGTs increased intestinal 7-ketolithocholic acid and tauroursodeoxycholic acid via 7α/β-hydroxysteroid dehydrogenase (7α/βHSDH), while reducing deoxycholic acid (DCA) and taurodeoxycholic acid through inhibition of bile acid 7α-dehydratase (BaiE), leading to lower hepatic DCA. Six intestinal components of HGTs interacted with 7αHSDH, 7βHSDH, and BaiE, which are expressed in the bacterial genera altered by HGTs. <b>Conclusions</b>: HGTs alleviate NASH fibrosis by reshaping the gut microbiome, acting on microbial BA-metabolizing enzymes, and regulating the BA metabolism in the liver and gut.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}