Search Results (470)

Background/Objectives: Atherogenic dyslipidemia is a major cardiometabolic risk factor characterized by elevated circulating triglycerides (TGs), reduced HDL-C, and increased levels of atherogenic lipoproteins. Curcumin, a polyphenolic compound considered the main bioactive component of turmeric (Curcuma longa), has attracted growing interest because of its potential lipid-modifying and anti-inflammatory properties. This scoping review aimed to evaluate evidence from randomized controlled trials (RCTs) on the efficacy of curcumin supplementation in the management of atherogenic dyslipidemia and to summarize current mechanistic evidence related to curcumin absorption, metabolism, and regulation of lipid homeostasis. Methods: A PRISMA-ScR-guided scoping review was performed across five databases (PubMed, Scopus, Web of Science, Cochrane Library, and Embase). RCTs evaluating curcumin supplementation in atherogenic dyslipidemia or related cardiometabolic conditions were systematically identified and synthesized. Mechanistic and preclinical evidence was identified through separate topic-specific searches of PubMed, Scopus, and Web of Science, supplemented by citation searching, and was synthesized narratively. Results: Twenty-two RCTs published between 2008 and 2025 were included. Most studies involved patients with cardiometabolic disorders, including type 2 diabetes mellitus with hyperlipidemia, metabolic syndrome, and polycystic ovary syndrome. Curcumin supplementation, administered in various formulations and dosages, showed overall favorable effects on plasma lipid profiles, particularly TGs and LDL-C, although the magnitude of these effects varied across studies. Mechanistic and preclinical evidence suggested that curcumin may modulate multiple pathways involved in lipid homeostasis, including intestinal cholesterol uptake, hepatic lipogenesis, cholesterol synthesis, fatty acid oxidation, bile acid metabolism, and reverse cholesterol transport. Conclusions: Current evidence suggests that curcumin may improve atherogenic lipid profiles through pleiotropic effects on lipid metabolism and cholesterol homeostasis. The clinical efficacy of curcumin appears to depend substantially on formulation-related bioavailability. Despite inter-study heterogeneity, curcumin shows potential as an adjunctive strategy for the management of atherogenic dyslipidemia and associated metabolic disorders. Full article

Emerging evidence links gut microbiota (GM) dysbiosis to hyperuricemia (HUA). The GM plays a critical role in regulating host health and homeostasis by producing a diverse array of metabolites, including short-chain fatty acids, bile acids and uremic toxins. Dysregulation of the microbial metabolite profile has been implicated in the pathogenesis of HUA. Given the urgent need for green and safe urate-lowering therapies for HUA, recent years have seen an increasing focus on interpreting the ability of natural products to modulate these microbial metabolites. Such interventions enhance beneficial metabolites and suppress uremic toxins, thereby alleviating HUA through coordinated regulation of urate transporters, restoration of intestinal barrier integrity, reprogramming of systemic metabolic disturbances, and inhibition of inflammation via Toll-like receptor 4 (TLR4)/ nuclear factor kappa B (NF-κB), Janus kinase (JAK)/ signal transducer and activator of transcription (STAT), and Phosphatidylinositol-3-kinase (PI3K)/ protein kinase B (AKT) pathways. Furthermore, a comprehensive translational roadmap has been proposed, grounded in a critical appraisal of current trial limitations. Overall, this review consolidates evidence for the protective effects of natural products against HUA and related comorbidities, with an emphasis on GM-derived metabolites, aiming to expand clinical applications and provide insights for future studies. Full article

Olive oil, particularly virgin (VOO) and extra-virgin olive oil (EVOO), is a central component of the Mediterranean diet and has been associated with cardiometabolic, anti-inflammatory, and intestinal health benefits. Increasing evidence suggests that these effects may involve interactions with the gut microbiota, intestinal barrier, and host inflammatory pathways. This narrative review summarizes current evidence on the impact of olive oil, olive-derived phenolics, and olive oil-rich dietary patterns on gut microbiota modulation, barrier function, inflammatory bowel diseases, and related systemic outcomes. The available literature indicates that olive oil may interact with the gut ecosystem through both its oleic acid-rich lipid matrix and its minor phenolic fraction. VOO and EVOO appear more consistently associated than refined oils with microbial or microbial metabolite profiles related to saccharolytic metabolism, short-chain fatty acid production, mucus-layer dynamics, and anti-inflammatory intestinal environments. Olive-derived phenolics, including hydroxytyrosol, tyrosol, oleuropein derivatives, and oleocanthal, can undergo microbial biotransformation and may influence bile acid metabolism, epithelial barrier integrity, and inflammatory signaling. Whole EVOO evidence is strongest in experimental colitis models, whereas human evidence mainly supports effects on postprandial endotoxemia, lipid oxidation, and selected inflammatory markers. However, findings remain heterogeneous and depend on oil quality, phenolic composition, comparator fat, dietary context, and host condition. Well-controlled human studies directly comparing EVOO, VOO, refined olive oil, and oleic acid-rich controls are needed to clarify reproducible microbiota-mediated effects and their relevance to intestinal and systemic health. Full article

Alterations in microbiota, transcript and metabolites are critical to intestinal homeostasis and host health. This study used a combination of 16s rRNA, transcriptome sequencing and liquid chromatography–mass spectrometry to investigate intestinal microbiota, genes and metabolic profiles in the ileum of Hu sheep fed broccoli extract. Here, we randomly allocated 14 Hu sheep to two diets: a basal diet without any supplementation (NC) and a basal diet supplemented with 200 mg/kg broccoli tail (BT). After 60 days of treatment, blood and jejunal samples were collected for serum biochemical indicators and multi-omics analysis. In this study, the extract of broccoli tails had a significant effect on the serum biochemical indicators, including white blood cells, red blood cells, mean corpuscular volume, mean corpuscular hemoglobin concentration, mean platelet volume, triglycerides and total protein in Hu sheep (p < 0.05). Transcriptomic analysis showed that the 672 differentially expressed genes between the NC and BT groups were primarily enriched in linoleic acid metabolism, steroid hormone biosynthesis, and cholesterol metabolism. Metabolomics analysis using Kyoto Encyclopedia of Genes and Genomes enrichment showed that the 41 differentially abundant metabolites were mainly enriched in bile secretion, vitamin B6 metabolism, and the mTOR signaling pathway. 16S rRNA sequencing results indicated that the extract of broccoli tails increased the relative abundance of Peptostreptococcaceae and decreased the relative abundance of Lachnospiraceae, Lachnospirales, and Bacteroidaceae. Integrated transcriptome, metabolome, and microbiome analysis showed that the gut microbiota and host transcriptomic changes may participate in systemic metabolic regulation by modulating amino acid metabolism, lipid signal transduction, nucleotide metabolism, and vitamin B6-related metabolic pathways. These findings demonstrate that the extract of broccoli tails modulates intestinal gene expression, systemic metabolism, and gut microbial ecology in Hu sheep, providing new insights into the utilization of agricultural byproducts as a functional feed supplement for ruminants. Full article

The circadian rhythm is an internal timing system formed by the body’s adaptation to the Earth’s rotation, which helps maintain homeostasis by regulating physiological, metabolic, and behavioral activities. The gut microbiota (GM), the largest microbial ecosystem in the human body, exhibits a bidirectional regulatory relationship with the host circadian clock. Emerging evidence indicates that circadian rhythm disruption (CRD) is linked to disturbances in the diurnal oscillations and compositional balance of the GM, accompanied by reduced short-chain fatty acid levels, increased lipopolysaccharide leakage, and altered tryptophan metabolism. These microbial abnormalities may be involved in anxiety-like behaviors through three major pathways: neuroendocrine (hyperactivation of the HPA axis), immune (microglia-mediated neuroinflammation), and neurotransmitter (imbalance of the serotonergic and dopaminergic systems). Conversely, microbial metabolites such as butyrate and secondary bile acids may reciprocally regulate peripheral clock gene expression, forming a complex “circadian rhythm–GM–anxiety” interaction network. This review summarizes the molecular basis of circadian–GM interactions, potential GM-mediated mechanisms linking CRD with anxiety, and emerging intervention strategies including chrononutrition (time-restricted feeding, sequential nutrient intake), microbiota-targeted therapies (probiotics/prebiotics, fecal microbiota transplantation), and light therapy and melatonin supplementation. Future directions should focus on cell-specific mechanisms using single-cell and spatial transcriptomics, developing personalized interventions that integrate chronotype and microbiome profiling, and conducting large-scale randomized controlled trials to facilitate clinical translation. This review provides a framework for understanding the integrative role of circadian biology and gut microbiota in anxiety and may help develop precision intervention paradigms. Full article

Background/Objectives: The gut–brain axis and systemic metabolic dysregulation are increasingly implicated in Alzheimer’s disease (AD) pathogenesis. This study aimed to characterize gut microbiota and plasma metabolomic profiles associated with amyloid pathology and cognitive impairment in patients with mild cognitive impairment (MCI). Methods: A cross-sectional multi-omics baseline analysis was performed in 47 MCI patients enrolled in a randomized, double-blind, crossover dietary intervention trial (NCT05029765). Gut microbiota composition was assessed by 16S rRNA sequencing (n = 47), and plasma metabolomics by untargeted LC-MS/MS (n = 45 after exclusion of two PCA-defined metabolomic outliers). Patients were stratified according to plasma amyloid-beta 42/40 ratio (BA42/40) and ADAScog11 score, representing complementary biomarkers of amyloid burden and cognitive impairment, respectively. Results: Higher amyloid burden and worse cognitive performance were associated with significant gut microbiota alterations, including increased alpha diversity and distinct beta diversity profiles. Differential abundance analyses consistently showed enrichment of Bacteroides-associated taxa and Akkermansia, alongside depletion of short-chain fatty acid-producing genera such as Faecalibacterium, Blautia, and Phascolarctobacterium. Plasma metabolomics identified a coherent signature associated with elevated BA42/40, characterized by accumulation of secondary bile acid sulfates and depletion of sphingolipids, neuroactive steroids, and anti-inflammatory lipid mediators, including pregnenolone sulfate, resolvin E1, and anandamide. A valid OPLS-DA discriminant model was obtained for BA42/40, whereas no predictive model was achieved for ADAScog11. Critically, this dissociation, characterized by significant microbiota differences but no metabolomic separation for ADAScog11, is itself an informative finding, suggesting that gut microbiota dysbiosis and plasma metabolomic alterations are not equally coupled to both dimensions of MCI pathophysiology. Conclusions: MCI patients with greater amyloid pathology and cognitive impairment exhibited gut microbiota dysbiosis. However, metabolic associations were observed only for BA42/40, but not for ADAScog11. These findings provide a mechanistic framework for evaluating the impact of Mediterranean diet and probiotic interventions in the longitudinal phase of the trial. Full article

An 8-week feeding trial was conducted to investigate the regulatory effects of dietary chitosan oligosaccharide (COS), chlorogenic acid (CGA), and thymopeptide (TH) on the growth performance, antioxidant capacity, and metabolism of juvenile Rhinogobio ventralis. A control group (CON) and three treatment groups (COS, CGA, TH) were established, and the underlying molecular mechanisms were analyzed by transcriptomics and metabolomics. The results showed that dietary supplementation with COS, CGA, and TH significantly improved weight gain rate, specific growth rate, and feed utilization efficiency, with COS exhibiting the strongest growth-promoting effect. COS also significantly increased hepatic catalase and superoxide dismutase activities and decreased malondialdehyde content, indicating a marked antioxidant effect, whereas CGA and TH showed no significant effects on these parameters. Transcriptomic analysis revealed significant differences in gene expression profiles among the groups, with commonly enriched pathways including the FoxO signaling pathway, fatty acid biosynthesis, and nicotinate and nicotinamide metabolism. Metabolomic analysis showed that the three additives significantly reshaped the hepatic metabolic profiles: COS mainly activated anabolic metabolism, CGA predominantly suppressed metabolism, and TH exhibited bidirectional regulation, with bile secretion, neuroactive ligand–receptor interaction, and the Fc epsilon RI signaling pathway commonly enriched in all three groups. Integrative KEGG pathway analysis based on transcriptomic and metabolomic predictions further identified the FoxO signaling pathway and neuroactive ligand–receptor interaction as common targets shared by all three additives. In conclusion, COS, CGA, and TH improve the health status of R. ventralis through differential regulation of immune–metabolic networks. Among them, COS is the most suitable feed additive for growth promotion and antioxidant protection in this species. Full article

Alcohol-related liver disease (ALD) poses a significant global health burden, driven by complex mechanisms including oxidative stress, inflammation, and gut–liver axis disruption. While the individual roles of gut microbiota dysbiosis and ageing in ALD pathogenesis are increasingly recognized, their synergistic interaction remains poorly understood. This review synthesizes current evidence to argue that there is an interaction between ageing and the gut microbiota that collectively amplifies progression of ALD. Specifically, ageing promotes gut dysbiosis through immunosenescence (e.g., reduced IgA diversification and antimicrobial peptide decline), intestinal barrier failure, and altered microbial metabolite profiles (e.g., decreased short-chain fatty acids and dysregulated bile acid metabolism). Conversely, dysbiosis-derived metabolites and endotoxins modulate ageing-related signaling pathways, including SIRT1, FOXO, and Nrf2, thereby accelerating hepatic cellular senescence, inflammation, and fibrogenesis. Furthermore, we also discussed the typical microbial changes in ALD. These include an increase in the Proteobacteria, a decrease in the Bacteroidetes, as well as imbalances in fungi and viruses. In ageing, similar but distinct shifts occur, such as reduced microbial diversity, decreased short-chain fatty acid producers, and increased intestinal permeability. Therapeutic strategies targeting the gut microbiota (probiotics, fecal microbiota transplantation) or ageing-related pathways (SIRT1 activators) hold promise. Future research priorities include validating ageing-associated microbial signatures as predictors of ALD progression and testing microbiota-targeted interventions in aged preclinical models. Collectively, this review identifies the microbiota–ageing axis as a tractable therapeutic target for ALD and provides a framework for future mechanistic and translational studies. Full article

Reducing reliance on supplemental fish oil is central to sustainable aquaculture, but the molecular consequences of replacing it with vegetable oils remain poorly characterized in the juvenile Chinese soft-shelled turtle (Pelodiscus sinensis). We evaluated whether full substitution of the supplemental dietary fish oil (FO) with linseed oil (LO) or soybean oil (SO) compromises hepatic lipid metabolism in Pelodiscus sinensis. Three isonitrogenous and isolipidic diets, sharing identical fish meal and other ingredient bases and differing only in the supplemental lipid (4% FO, LO or SO), were fed to triplicate groups of juvenile turtles (initial body weight 55.0 ± 0.05 g) for 8 weeks. Growth performance, survival, feed conversion ratio, and serum biochemistry were unaffected. However, both vegetable oil diets altered tissue fatty acid composition, raising n-6 PUFA and lowering n-3 LC-PUFA and the n-3/n-6 ratio in liver and muscle (muscle EPA and DHA each decreased by approximately 40%); the SO group additionally exhibited elevated hepatic malondialdehyde, whereas hepatic lipid droplet area and lipid content did not differ significantly among groups. Liver transcriptomic profiling identified 262 (LO vs. FO) and 214 (SO vs. FO) differentially expressed genes, converging on lipid storage and bile acid metabolism. RT-qPCR confirmed the up-regulation of PLIN3, G0S2 and APOF and the down-regulation of CYP7A1. Over 8 weeks, replacement of supplemental FO maintained growth without overt impairment while altering tissue fatty acid profiles and the hepatic expression of key lipid metabolism genes. Full article

Beyond their established role in lipid digestion, bile acids function as key metabolic and immune signaling molecules. This review synthesizes recent advances in bile acid metabolism within the context of gout and hyperuricemia, proposing a gut–liver–joint crosstalk framework. Dysregulated bile acid metabolism—characterized by a reduced total bile acid pool, decreased hydrophobic secondary bile acids, elevated 12α-hydroxy bile acids, and impaired enterohepatic circulation—has been mechanistically linked to both hepatic urate overproduction via the PPAR-α/xanthine oxidase pathway and monosodium urate crystal-induced NLRP3 inflammasome activation, although human causal evidence remains to be established. The nuclear receptor FXR suppresses NLRP3 at the transcriptional level, while the membrane receptor TGR5 acts post-translationally through Cyclic adenosine monophosphate/Protein Kinase A (cAMP/PKA) and Glucagon-like peptide-1 (GLP-1) signaling. Gut microbiota dysbiosis amplifies these abnormalities through a vicious cycle of reduced bile acid signaling, increased intestinal permeability, and systemic endotoxemia. Based on these insights, we summarize five therapeutic strategies: FXR modulators, TGR5 agonists, microbiota-based interventions, natural products, and ursodeoxycholic acid replacement therapy. Future research should prioritize gout-specific preclinical models, clinical trials of TGR5 agonists, standardized microbiota-based therapies, dual-target molecules, and personalized patient stratification based on bile acid profiles. Full article

Saccharomyces cerevisiae FOSU-QQT (SC.QQT), isolated from pineapple pomace wine, exhibits favorable aroma-producing capabilities. In this study, we performed integrated genomic and phenotypic analyses to comprehensively evaluate its safety profile, probiotic potential, and aroma-producing characteristics. Whole-genome sequencing (WGS) assembly predicted a genome size of 30,256,254 bp, encompassing 12,899 genes with a total coding length of 22,062,659 bp and an average GC content of 37.30%. Preliminary safety assessments, including hemolysis tests, antibiotic susceptibility profiling, and antibacterial activity assays, were complemented by in silico screening for antibiotic resistance-associated genes. Functional tolerance assays, specifically resistance to simulated gastrointestinal fluid, acid stress, and bile salts, demonstrated that SC.QQT exhibited robust survival under physiologically relevant gastrointestinal conditions. Collectively, these findings support its potential as a promising probiotic candidate with notable resilience, although further in vivo validation is required to confirm its application value. Additionally, gas chromatography–mass spectrometry (GC–MS) analysis of volatile compounds in pineapple pomace wine indicated that the presence of aroma-related genes in SC.QQT may enhance overall flavor complexity and intensify fruity aromatic notes during fermentation, underscoring its distinctive utility in fruit wine bioprocessing. Full article

Background: Phosphatidylcholine (PC) is a major phospholipid that contributes to intestinal barrier protection and is essential for hepatic secretion of lipids and bile acids. Because inflammatory bowel disease (IBD) and primary sclerosing cholangitis (PSC) are closely linked, we hypothesized that individual serum PC species would reflect disease activity. We therefore investigated whether serum PC profiling could identify clinically useful biomarkers across the gut–liver axis. Methods: Serum concentrations of 21 PC species were quantified by direct flow injection high-resolution mass spectrometry in 16 healthy controls, 57 patients with IBD, and 20 patients with PSC. Results: In IBD, multiple serum PC species were inversely associated with inflammatory activity, showing negative correlations with serum C-reactive protein and fecal calprotectin. Patients with fecal calprotectin concentrations above the diagnostic cut-off of 120 µg/g had lower levels of PC 34:3, 36:1, 36:2, 36:3, 36:4, 36:5, 38:3, 38:4, 38:5, 38:7, 40:5, and 40:6, as well as lower total PC. In contrast, in PSC, PC 30:0, 32:0, 32:1, and 34:1 were increased compared with IBD and correlated positively with gamma-glutamyltransferase and alkaline phosphatase. Furthermore, these shorter-chain PC species as well as PC 36:1 were markedly elevated in PSC with advanced liver fibrosis compared with PSC without fibrosis. Conclusions: Serum PC species show a reciprocal disease-associated pattern in IBD and PSC. In IBD, lower concentrations of predominantly unsaturated PC species are associated with active intestinal inflammation, whereas in PSC, higher concentrations of shorter-chain PC species are associated with cholestatic injury and advanced liver fibrosis. IBD and PSC exhibit opposing serum PC signatures, suggesting that dysregulated PC metabolism is a pathophysiological feature of intestinal inflammation and PSC-associated liver fibrosis. Full article

Myopia is increasingly recognized as an inflammatory ocular disease. Vitamin D₃ is a potential modulator of the gut–eye axis, but its role in inflammation-induced myopia remains unclear. This study investigated whether vitamin D₃ supplementation attenuates myopia progression by regulating retinal inflammation, gut microbiota composition, and microbiota-derived metabolites in a TGF-β2–induced myopia model. Three-week-old Brown Norway rats received weekly periocular TGF-β2 injections with or without daily oral vitamin D₃, and myopia development was evaluated on days 1 and 21 by axial length and refractive error. Cecal contents were analyzed for α- and β-diversity and taxonomic differences, and day-21 serum underwent untargeted metabolomic profiling of microbiota-derived metabolites, including bile acids and imidazole derivatives; Spearman correlation linked microbial or metabolic alterations with myopia progression. TGF-β2 induced axial elongation, myopic refractive shifts, and upregulated retinal pro-inflammatory cytokines (p-NFκB, IL-1β, TNF-α), while vitamin D₃ supplementation markedly attenuated myopia progression and retinal inflammation. Cecal α-diversity did not differ among control, vitamin D₃, TGF-β2, and TGF-β2+vitamin D₃ groups, but vitamin D₃ significantly reshaped β-diversity and reduced the Firmicutes/Bacteroidota ratio. Distinct metabolite profiles were observed, with the vitamin D₃ group showing reduced hyodeoxycholic acid and elevated imidazole derivatives (imidazolepropionic and methylimidazoleacetic acids). Vitamin D₃ supplementation attenuated myopia progression by reducing retinal inflammation and concurrently reshaping the gut microbiome and its metabolites compared to the control and myopic groups. These results underscore the potential of vitamin D₃ to modulate the gut–retina axis as a nutritional approach for mitigating myopia development. Full article

Background/Objectives: Ultra-processed foods (UPFs) are increasingly recognized as dietary exposures associated with cardiometabolic, hepatic, and neurocognitive outcomes. However, UPFs are often treated mainly as nutrient-poor foods, whereas their processing-related features may perturb gut–liver–brain communication. This review examines whether metabolic dysfunction-associated steatotic liver disease (MASLD) can be conceptualized as a hepatic metabolic amplifier linking UPF exposure to cognitive aging. Methods: We conducted a structured narrative search of PubMed/MEDLINE, Web of Science Core Collection, and Scopus from January 2010 to 11 May 2026 across four evidence modules: UPFs and MASLD/NAFLD; UPFs and cognitive aging or dementia; UPFs and gut–liver–brain mechanisms; and MASLD/NAFLD and cognitive aging. Representative studies were prioritized according to direct relevance to the proposed axis, study design, exposure and outcome validity, mechanistic specificity, and contribution to major evidence gaps. Results: Observational and mechanistic evidence links higher UPF consumption with liver steatosis, MASLD/NAFLD-related outcomes, cognitive decline, cognitive impairment, stroke, and dementia-related outcomes, although causality remains incompletely established and residual confounding is important. Candidate pathways include food-matrix disruption, rapid eating, displacement of microbial substrates, selected additives and processing-derived compounds, intestinal barrier dysfunction, metabolic endotoxemia, bile acid signaling, hepatic lipotoxicity, systemic inflammation, vascular dysfunction, and neuroimmune activation. Many pathways overlap with general cardiometabolic dysfunction; the processing-centered contribution lies in positioning industrial formulation as an upstream exposure and MASLD as a hepatic node that may amplify gut-derived and metabolic signals relevant to brain aging. Conclusions: A processing-centered gut–liver–brain framework integrates UPFs, MASLD, and cognitive aging as linked metabolic-aging phenomena. Future studies should test UPF substitution using liver imaging, microbiome profiling, metabolomics, bile acid and inflammatory biomarkers, neuroimaging, and cognitive assessment. Full article

Background/Objectives: The emergence of drug-resistant Plasmodium falciparum highlights the need for new antiplasmodial compounds with distinct mechanisms of action. Microbial secondary metabolites, particularly from Streptomyces species, remain important sources of bioactive molecules. This study aimed to evaluate antiplasmodial metabolites associated with a Mongolian Streptomyces isolate. Methods: Streptomyces sp. strain D10 was isolated from Mongolian soil samples and extracted with ethyl acetate. Bioassay-guided fractionation was performed, followed by LC–HRMS analysis and GNPS-based spectral dereplication. Antiplasmodial activity was evaluated against P. falciparum 3D7, K1, and Dd2 strains using a SYBR Green I assay. Cytotoxicity was assessed in HSF cells. Stage-specific susceptibility assays were conducted using synchronized 3D7 parasites. Comparative docking analyses against β-hematin and the chloroquine resistance transporter (PfCRT), together with target prediction and molecular docking analyses, were performed to explore potential mechanisms. In vivo efficacy was evaluated using a Plasmodium yoelii 17XNL mouse model. Results: Fractionation yielded an active fraction (C2), and LC–HRMS and GNPS-based dereplication suggested a bile acid-like metabolite, with ursodeoxycholic acid (UDCA) returned as a putative spectral library candidate associated with fraction C2. Fraction C2 and UDCA showed comparable antiplasmodial activity against P. falciparum 3D7 (IC₅₀ = 6.55 ± 3.00 and 4.68 ± 0. 65 µg/mL, respectively) without detectable cytotoxicity up to 200 µg/mL. Activity was retained against multidrug-resistant K1 and Dd2 strains. Stage-specific assays demonstrated inhibitory activity across ring, trophozoite, and schizont stages without significant stage-dependent differences. Comparative docking analyses suggested interaction profiles distinct from chloroquine in β-hematin and PfCRT models. Additional docking analyses identified PfGluPho, PfMAPK, and PfPFT-β as potential targets. In vivo, UDCA reduced parasitemia in a dose-dependent manner without significant toxicity. Conclusions: UDCA exhibited moderate antiplasmodial activity across in vitro, in silico, and in vivo evaluations with a favorable selectivity profile, supporting further investigation of bile acid-like metabolites as potential antimalarial scaffolds. Full article