Search Results (1,749)

Background and Objectives: The uric acid to HDL-cholesterol ratio (UHR) has recently emerged as a promising biomarker reflecting systemic inflammation and metabolic disturbances. Elevated liver transaminases are clinical indicators of hepatic injury and underlying metabolic dysfunction. Many Middle Eastern countries face constrained clinical and laboratory resources, where access to comprehensive diagnostic tools may be limited. In such settings, identifying simple and easily accessible markers could offer significant practical value in detecting and monitoring health disorders. This study investigates the potential association between UHR and elevated liver transaminases levels in the Saudi general population. Materials and Methods: This retrospective cross-sectional study included 9618 subjects, and the association between the UHR and elevated liver transaminases, alanine transaminase (ALT), and aspartate transaminase (AST), was comprehensively analysed. In addition, the study assessed risk indicators including the prevalence ratio (PR) and odds ratio (OR) as well as the diagnostic accuracy of UHR and C-reactive protein (CRP) in detecting liver transaminases abnormalities, with analyses stratified by age and gender. Results: UHR was significantly elevated in subjects with increased ALT and AST activities, and this pattern was consistent across all age and gender categories. High UHR was significantly associated with elevated ALT (OR = 2.32, 95% CI: 2.12–2.53, p < 0.001) and AST (OR = 1.38, 95% CI: 1.25–1.52, p < 0.001), with stronger associations observed in males and for ALT activity. In addition, elevated UHR was more prevalent among individuals with increased liver transaminase activities. Receiver operating characteristic (ROC) analysis showed that UHR outperformed CRP in identifying elevated liver transaminases, with better discriminative ability for ALT than AST activity. Conclusions: These findings highlight a significant association between UHR and liver transaminase abnormalities in the general population, underscoring the potential utility of UHR as a simple and accessible indicator for liver function assessment in clinical settings. Full article

Barium chloride (BaCl₂), a known environmental pollutant, induces organ-specific oxidative stress through disruption of redox homeostasis. This study evaluated the protective effects and safety profile of sodium copper chlorophyllin (SCC) and ascorbic acid (ASC) against BaCl₂-induced oxidative damage in the liver and brain of mice using a two-phase experimental protocol. Animals received either SCC (40 mg/kg), ASC (160 mg/kg), or their combination for 14 days prior to BaCl₂ exposure (150 mg/L in drinking water for 7 days), allowing evaluation of both preventive and therapeutic effects. Toxicological and behavioral assessments confirmed the absence of systemic toxicity or neurobehavioral alterations following supplementation. Body weight, liver and kidney indices, and biochemical markers (Aspartate Aminotransferase (ASAT), Alanine Aminotransferase (ALAT), creatinine) remained within physiological ranges, and no anxiogenic or locomotor effects were observed. In the brain, BaCl₂ exposure significantly increased SOD (+49%), CAT (+66%), GPx (+24%), and GSH (+26%) compared to controls, reflecting a robust compensatory antioxidant response. Although lipid peroxidation (MDA) showed a non-significant increase, SCC, ASC, and their combination reduced MDA levels by 42%, 37%, and 55%, respectively. These treatments normalized antioxidant enzyme activities and GSH, indicating an effective neuroprotective effect. In contrast, the liver exhibited a different oxidative profile. BaCl₂ exposure increased MDA levels by 80% and GSH by 34%, with no activation of SOD, CAT, or GPx. Histological analysis revealed extensive hepatocellular necrosis, vacuolization, and inflammatory infiltration. SCC significantly reduced hepatic MDA by 39% and preserved tissue architecture, while ASC alone or combined with SCC exacerbated inflammation and depleted hepatic GSH by 71% and 78%, respectively, relative to BaCl₂-exposed controls. Collectively, these results highlight a differential, organ-specific response to BaCl₂-induced oxidative stress and the therapeutic potential of SCC and ASC. SCC emerged as a safer and more effective agent, particularly in hepatic protection, while both antioxidants demonstrated neuroprotective effects when used individually or in combination. Full article

The utilisation of edible insects for human nutrition is a long-standing practice in many parts of the globe, and is being gradually introduced into countries without an entomophagic tradition as well. These unconventional sources of protein of animal origin have arisen as a sustainable alternative to other animal protein sources, such as meat. This review intends to present the compilation of data in the scientific literature on the chemical composition and nutritional value of the bee brood of A. mellifera species and subspecies as edible foods. For this, a comprehensive search of the scientific literature was carried out using the databases ScienceDirect, Scopus, Pub-Med, BOn, and SciELO. Appropriate keywords were used for the search to reach the research works that addressed the topics of the review. The results showed that bee brood has considerable quantities of protein, fat and carbohydrates. The most abundant amino acids are leucine and lysine (these two being essential amino acids) and aspartic acid, glutamic acid, and proline (these three being non-essential amino acids). As for the fatty acids, bee broods contain approximately equal fractions of saturated and monounsaturated fatty acids, while the polyunsaturated fatty acids are negligible. The dietary minerals present in higher quantities are potassium, phosphorus, and magnesium, and the most abundant vitamins are vitamin C and niacin; choline is also present, although it is not a true vitamin. Although bee brood from A. mellifera has potential for human consumption as a nutrient-rich food, there are still many aspects that need to be further studied in the future, such as safety and hazards linked to possible regular consumption. Full article

Although exercise is known to exert anti-inflammatory effects in neurodegenerative diseases, its specific impact and underlying mechanisms in Parkinson’s disease (PD) remain poorly understood. This study explores the effects of exercise on microglia-mediated neuroinflammation and apoptosis in a PD model, focusing on the role of irisin signaling in mediating these effects. Using a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model, we found that a 10-week treadmill exercise regimen significantly enhanced motor function, reduced dopaminergic neuron loss, attenuated neuronal apoptosis, and alleviated neuroinflammation. Exercise also shifted microglia from a pro-inflammatory to an anti-inflammatory phenotype. Notably, levels of irisin, phosphorylated AMP-activated protein kinase (p-AMPK), and sirtuin 1 (Sirt1), which were decreased in the PD brain, were significantly increased following exercise. These beneficial effects were abolished by blocking the irisin receptor with cyclic arginine–glycine–aspartic acid–tyrosine–lysine (cycloRGDyk). Our results indicate that exercise promotes neuroprotection in PD by modulating microglial activation and the AMPK/Sirt1 pathway through irisin signaling, offering new insights into exercise-based therapeutic approaches for PD. Full article

Background: Environmental exposures, such as per- and polyfluoroalkyl substances (PFAS), in conjunction with social and behavioral factors, can significantly impact liver health. This research investigates the combined effects of PFAS (perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), alcohol consumption, smoking, income, and education on liver function among the U.S. population, utilizing data from the 2017–2018 National Health and Nutrition Examination Survey (NHANES). Methods: PFAS concentrations in blood samples were analyzed using online solid-phase extraction combined with liquid chromatography–tandem mass spectrometry (LC-MS/MS), a highly sensitive and specific method for detecting levels of PFAS. Liver function was evaluated using biomarkers such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), total bilirubin, and the fatty liver index (FLI). Descriptive statistics and multivariable linear regression analyses were employed to assess the associations between exposures and liver outcomes. Bayesian Kernel Machine Regression (BKMR) was utilized to explore the nonlinear and interactive effects of these exposures. To determine the relative influence of each factor on liver health, Posterior Inclusion Probabilities (PIPs) were calculated. Results: Linear regression analyses indicated that income and education were inversely associated with several liver injury biomarkers, while alcohol use and smoking demonstrated stronger and more consistent associations. Bayesian Kernel Machine Regression (BKMR) further highlighted alcohol and smoking as the most influential predictors, particularly for GGT and total bilirubin, with posterior inclusion probabilities (PIPs) close to 1.0. In contrast, PFAS showed weaker associations. Regression coefficients were small and largely non-significant, and PIPs were comparatively lower across most liver outcomes. Notably, education had a higher PIP for ALT and GGT than PFAS, suggesting a more protective role in liver health. People with higher education levels tend to live healthier lifestyles, have better access to healthcare, and are generally more aware of health risks. These factors can all help reduce the risk of liver problems. Overall mixture effects demonstrated nonlinear trends, including U-shaped relationships for ALT and GGT, and inverse associations for AST, FLI, and ALP. Conclusion: These findings underscore the importance of considering both environmental and social–behavioral determinants in liver health. While PFAS exposures remain a long-term concern, modifiable lifestyle and structural factors, particularly alcohol, smoking, income, and education, exert more immediate and pronounced effects on hepatic biomarkers in the general population. Full article

Nonspecific toxicity to normal and malignant cells restricts the clinical utility of many anticancer drugs. In particular, anemia in cancer patients develops due to drug-induced toxicity to red blood cells (RBCs). The anticancer alkaloid, cepharanthine (CEP), elicits distinct forms of cell death including apoptosis and autophagy, but its cytotoxicity to RBCs has not been investigated. Colorimetric and fluorometric techniques were used to assess eryptosis and hemolysis in control and CEP-treated RBCs. Cells were labeled with Fluo4/AM and annexin-V-FITC to measure Ca²⁺ and phosphatidylserine (PS) exposure, respectively. Forward scatter (FSC) was detected to estimate cell size, and extracellular hemoglobin along with lactate dehydrogenase and aspartate transaminase activities were assayed to quantify hemolysis. Physiological manipulation of the extracellular milieu and various signaling inhibitors were tested to dissect the underlying mechanisms of CEP-induced RBC death. CEP increased PS exposure and hemolysis indices and decreased FSC in a concentration-dependent manner with prominent membrane blebbing. Although no Ca²⁺ elevation was detected, chelation of intracellular Ca²⁺ by BAPTA-AM reduced hemolysis. Whereas SB203580, D4476, acetylsalicylic acid, necrosulfonamide, and melatonin inhibited both PS exposure and hemolysis, staurosporin, L-NAME, ascorbate, caffeine, adenine, and guanosine only prevented hemolysis. Interestingly, sucrose had a unique dual effect by exacerbating PS exposure and reversing hemolysis. Of note, blocking KCl efflux augmented PS exposure while aggravating hemolysis only under Ca²⁺-depleted conditions. CEP activates Ca²⁺-independent pathways to promote eryptosis and hemolysis. The complex cytotoxic profile of CEP can be mitigated by targeting the identified modulatory pathways to potentiate its anticancer efficacy. Full article

Experimental and theoretical studies were applied to investigate the adsorption properties of testagen (KEDG) peptide on copper surfaces in sodium chloride solution and, implicitly, its inhibition efficiency (IE) on metal corrosion. The tetrapeptide synthesized from the amino acids lysine (Lys), glutamic acid (Glu), aspartic acid (Asp), and glycine (Gly), named as H-Lys-Glu-Asp-Gly-OH, achieved an inhibition efficiency of around 86% calculated from electrochemical measurements, making KEDG a promising new copper corrosion inhibitor. The experimental data were best fitted to the Freundlich adsorption isotherm. The standard free energy of adsorption ($\mathsf{\Delta }{\mathrm{G}}_{\mathrm{a}\mathrm{d}\mathrm{s}}^{\mathrm{o}}$) reached the value of −30.86 kJ mol⁻¹, which revealed a mixed action mechanism of tetrapeptide, namely, chemical and physical spontaneous adsorption. The copper surface characterization was performed using optical microscopy and SEM/EDS analysis. In the KEDG presence, post-corrosion, SEM images showed a network surface morphology including microdeposits with an acicular appearance, and EDS analysis highlighted an upper surface layer consisting of KEDG, sodium chloride, and copper corrosion compounds. The computational study based on DFT and Monte Carlo simulation confirmed the experimental results and concluded that the spontaneous adsorption equilibrium establishment was the consequence of the contribution of noncovalent (electrostatic, van der Waals) interactions and covalent bonds. Full article

Background: During food processing and storage, traditional protein-based delivery systems encounter significant challenges in maintaining the structural and functional integrity of bioactive compounds, primarily due to their temporal instability. Methods: In this study, a nanocomposite hydrogel was prepared through the co-assembly of a self-assembling peptide, 9-Fluorenylmethoxycarbonyl-phenylalanine-arginine-glycine-aspartic acid-phenylalanine (Fmoc-FRGDF), and hyaluronic acid (HA). The stability of this hydrogel as a quercetin (Que) delivery carrier was systematically investigated. Furthermore, the impact of Que co-assembly on the microstructural evolution and physicochemical properties of the hydrogel was characterized. Concurrently, the encapsulation efficiency (EE%) and controlled release kinetics of Que were quantitatively evaluated. Results: The findings indicated that HA significantly reduced the storage modulus (G′) from 256.5 Pa for Fmoc-FRGDF to 21.1 Pa with the addition of 0.1 mg/mL HA. Despite this reduction, HA effectively slowed degradation rates; specifically, residue rates of 5.5% were observed for Fmoc-FRGDF alone compared to 14.1% with 0.5 mg/mL HA present. Notably, Que enhanced G′ within the ternary complex, increasing it from 256.5 Pa in Fmoc-FRGDF to an impressive 7527.0 Pa in the Que/HA/Fmoc-FRGDF hydrogel containing 0.1 mg/mL HA. The interactions among Que, HA, and Fmoc-FRGDF involved hydrogen bonding, electrostatic forces, and hydrophobic interactions; furthermore, the co-assembly process strengthened the β-sheet structure while significantly promoting supramolecular ordering. Interestingly, the release profile of Que adhered to the Korsmeyer–Peppas pharmacokinetic equations. Conclusions: Overall, this study examines the impact of polyphenol on the rheological properties, microstructural features, secondary structure conformation, and supramolecular ordering within peptide–polysaccharide–polyphenol ternary complexes, and the Fmoc-FRGDF/HA hydrogel system demonstrates a superior performance as a delivery vehicle for maintaining quercetin’s bioactivity, thereby establishing a multifunctional platform for bioactive agent encapsulation and controlled release. Full article

Background/Objectives: Sepsis-induced cardiomyopathy (SIC) is a serious clinical disorder with a high death rate. Qifu decoction (QFD) is a renowned traditional Chinese medicine with documented pharmacological actions, such as anti-inflammatory, anti-oxidant and anti-apoptosis activities, and it has good therapeutic effects on cardiovascular diseases. This study aimed to reveal the cardioprotective effects and underlying mechanisms of QFD against SIC. Methods: Electrocardiography, histopathological examination, and biochemical indicator determination were carried out to investigate the cardioprotective effects of QFD in the treatment of LPS-induced SIC mice. Metabolomics and network pharmacology strategies were employed to preliminarily analyze and predict the mechanisms of QFD against SIC. Molecular docking and Western blot were further applied to validate the core targets and potential pathways for the treatment of SIC in in vitro and in vivo models. Results: It was found that QFD considerably enhanced cardiac function; attenuated myocardial injury; and reduced the serum levels of LDH, CK-MB, IL-1β, and TNF-α by 28.7%, 32.3%, 38.6%, and 36.7%, respectively. Metabolomic analysis showed that QFD could regulate seven metabolic pathways, namely, glutathione metabolism; alanine, aspartate, and glutamate metabolism; arachidonic acid metabolism; glycerophospholipid metabolism; purine metabolism; sphingolipid metabolism; and fatty acid metabolism. Network pharmacology suggested that the anti-SIC effect of QFD may be mediated through the TNF, toll-like receptor, NOD-like receptor, NF-κB, and PPAR signaling pathways. Additionally, 26 core targets were obtained. Molecular docking revealed that active ingredients such as formononetin, kaempferol, quercetin, and (R)-norcoclaurine in QFD had a high affinity for binding to PPARα and TLR4. Further Western blot validation indicated that QFD could regulate the protein levels of NLRP3, TLR4, NF-κB, IL-6, TNF-α, COX2, sPLA2, PPARα, CPT1B, and CPT2. Conclusions: This study demonstrates that QFD can alleviate SIC by suppressing the TLR4/NF-κB/NLRP3 inflammatory pathway and modulating impaired FAO through the activation of the PPARα/CPT pathway, highlighting QFD as a promising candidate drug for SIC treatment. Full article

Metabolome studies have already been carried out in patients with systemic sclerosis (SSc). However, polyneuropathy (PNP) as a complication of SSc has been overlooked in these studies. To the best of our knowledge, this is the first study to examine metabolic changes in SSc patients with PNP. Patients with SSc (n = 62) and a healthy control group (HC) (n = 72) were recruited from two Latvian hospitals. Blood plasma samples were collected and analyzed using an LC-MS-based targeted metabolomics workflow. Our plasma sample cohort consisted of 62 patients with SSc, 42% of whom had PNP. Differences between SSc patients and the HC group with fold changes > 2 were observed for aspartic acid, glutamic acid, valine, and citrulline, all of which were reduced. In contrast to the SSc to HC discrimination, no metabolites had a high fold change; only minor changes were observed using FC > 1.3. We identified elevated concentrations of kynurenine, asparagine, and alanine. Changes in metabolite regulation in patients with SSc, compared to controls, are not identical to those observed in SSc patients with PNP, with elevated concentrations of kynurenine and alanine specific to the SSc subgroup. SSc patients with PNP should probably be considered a distinct population with important metabolomic features. Full article

Background: The amylin receptor is a receptor for the peptide hormone amylin, and its activation is known to reduce body weight. The amylin receptor functions as a heterodimer complex that consists of the calcitonin receptor for peptide hormone calcitonin and an accessary protein. Although the structural information of amylin receptors is currently available, receptor–ligand binding studies that support the peptide binding mode for amylin receptors remain incomplete. Methods: Here, we introduced mutagenesis to the amylin receptor 1 extracellular domain and examined mutational effects on peptide binding affinity. We focused on several residues mainly from the peptide-binding pocket (D97, D101, E123, N124, and N135 of the calcitonin receptor). Two well-known peptide ligands for amylin receptors were used for this study: a salmon calcitonin fragment and an antagonist amylin analog AC413 fragment with Y25P mutation. Results: Among the introduced mutations, D101A and N135A mutations abolished peptide ligand binding, suggesting that these residues are critical for peptide interaction. The N124A mutation also significantly decreased the peptide binding affinity by more than 8-fold. Intriguingly, the N124D mutation restored the decreased affinity of the salmon calcitonin fragment, while it failed to restore the decreased affinity of the AC413 fragment. Structural analyses suggested that there was a potential role of salmon calcitonin serine 29 in the interaction with aspartate of the N124D mutation. Conclusions: This study validates the critical residues of the amylin receptor 1 extracellular domain for the interaction with C-terminal fragments of peptide ligands. This study also suggests that modulating receptor–ligand interaction is feasible by the modification of receptor amino acids near an interacting peptide ligand. Full article

Optimizing the metabolizable protein level in ruminant diets represents a promising strategy to increase nitrogen use efficiency and mitigate environmental pollution. This study explored the impacts of varying metabolizable protein (MP) levels on amino acid (AA) balance, nitrogen (N) utilization, and the ruminal microbiota in Hu lambs. Fifty-four female Hu lambs of 60 d old, with an average body weight (BW) of 18.7 ± 2.37 kg, were randomly allocated to three dietary MP groups: (1) low MP (LMP, 7.38% of DM), (2) moderate MP (MMP, 8.66% of DM), and (3) high MP (HMP, 9.93% of DM). Three lambs with similar BW within each group were housed together in a single pen, serving as one experimental replicate (n = 6). The feeding trial lasted for 60 days with 10 days for adaptation. The final BW of lambs in the MMP and HMP groups increased (p < 0.05) by 5.64% and 5.26%, respectively, compared to the LMP group. Additionally, lambs fed the MMP diet exhibited an 11.6% higher (p < 0.05) average daily gain than those in the LMP group. Increasing dietary MP levels enhanced (p < 0.05) N intake, urinary N, retained N, and percent N retained, but decreased apparent N digestibility (p < 0.05). Urinary uric acid, total purine derivatives, intestinally absorbable dietary protein, microbial crude protein, intestinally absorbable microbial crude protein, and actual MP supply all increased (p < 0.05) with higher MP values in the diet. The plasma concentrations of arginine, lysine, methionine, phenylalanine, threonine, aspartic acid, proline, total essential AAs, and total nonessential AAs were the lowest (p < 0.05) in the LMP group. In the rumen, elevated MP levels led to a significant increase (p < 0.05) in the ammonia N content. The relative abundances of Candidatus_Saccharimonas, Ruminococcus, and Oscillospira were the lowest (p < 0.05), whereas the relative abundances of Terrisporobacter and the Christensenellaceae_R-7_group were the highest (p < 0.05) in the MMP group. In conclusion, the moderate dietary metabolizable protein level could enhance growth performance, balance the plasma amino acid profiles, and increase nitrogen utilization efficiency in Hu lambs, while also altering the rumen bacterial community by increasing beneficial probiotics like the Christensenellaceae_R-7_group. Full article

Quercus acutissima seeds exhibit high desiccation sensitivity, posing significant challenges for long-term preservation. This study investigates the physiological and metabolic responses of soluble osmoprotectants—particularly soluble proteins and proline—during the desiccation process. Seeds were sampled at three critical moisture content levels: 38.8%, 26.8%, and 14.8%, corresponding to approximately 99%, 52%, and 0% germination, respectively. We measured germination ability, soluble protein content, and proline accumulation, and we performed untargeted metabolomic profiling using LC-MS. Soluble protein levels increased early but declined later during desiccation, while proline levels continuously increased for sustained osmotic adjustment. Metabolomics analysis identified a total of 2802 metabolites, with phenylpropanoids and polyketides (31.12%) and lipids and lipid-like molecules (29.05%) being the most abundant. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that differentially expressed metabolites were mainly enriched in key pathways such as amino acid metabolism, energy metabolism, and nitrogen metabolism. Notably, most amino acids decreased in content, except for proline, which showed an increasing trend. Tricarboxylic acid cycle intermediates, especially citric acid and isocitric acid, showed significantly decreased levels, indicating energy metabolism imbalance due to uncoordinated consumption without effective replenishment. The reductions in key amino acids such as glutamic acid and aspartic acid further reflected metabolic network disruption. In summary, Q. acutissima seeds fail to establish an effective desiccation tolerance mechanism. The loss of soluble protein-based protection, limited capacity for proline-mediated osmotic regulation, and widespread metabolic disruption collectively lead to irreversible cellular damage. These findings highlight the inherent metabolic vulnerabilities of recalcitrant seeds and suggest potential preservation strategies, such as supplementing critical metabolites (e.g., TCA intermediates) during storage to delay metabolic collapse and mitigate desiccation-induced damage. Full article

Social anxiety disorder (SAD) is characterized by fear and avoidance of social situations. Considering the reduced availability of conventional therapies, we aimed to improve our understanding of the biological mechanisms in SAD by evaluating gamma-aminobutyric acid (GABA) and other neurometabolites (including glutamate + glutamine/glutamix (Glx), N-acetyl aspartate (NAA), myo-inositol (mI), total choline (tCho), and total creatine (tCr) in the dorsomedial prefrontal cortex/anterior cingulate cortex (dmPFC/ACC), dorsolateral prefrontal cortex (dlPFC), and the insula). In this pilot study, we recruited 26 (age: 25.3 ± 5.0 years; 61.5% female) individuals with SAD and 26 (age: 25.1 ± 4.4 years; 61.5% female) sex-age-matched controls. Using proton magnetic resonance spectroscopy, we found that compared to the controls, GABA+ macromolecular signal (GABA+) in dlPFC (t = 2.63; p = 0.012) and Glx in the insula (Mann–Whitney U = 178.3; p = 0.024) were higher in the participants with SAD. However, no between-group differences were observed in dmPFC/ACC (t = 0.39; p = 0.699). Increased GABA+ in dlPFC could be explained by aberrant GABA transporters. In the insula, increased Glx may be associated with the dysfunction of glutamate transporters or decreased activity of glutamic acid decarboxylase in the GABAergic inhibitory neurons. However, these proposed mechanisms need to be further investigated in SAD. Full article

Background: Huang Qin Decoction (HQD) is a well-established Traditional Chinese Medicine (TCM) formulation recognized for its application in the treatment of colorectal cancer (CRC). However, the precise therapeutic mechanisms remain inadequately defined. Methods: This study integrates metabolomics from a mouse model and network pharmacology to screen potential targets and bio-active ingredients of HQD. The pharmacological activity of HQD for CRC was evidenced via single-cell RNA sequencing (scRNA-seq), molecular docking, and molecular dynamics simulations. Atomic force microscopy (AFM) assays and cellular experimental validation were used to confirm the relative mechanisms. Results: The metabolite profile undergoes significant alterations, with metabolic reprogramming evident during the malignant progression of CRC liver metastasis. Network pharmacology analysis identified that HQD regulates several metabolic pathways, including arginine biosynthesis, alanine, aspartate, and glutamate metabolism, nitrogen metabolism, phenylalanine metabolism, and linoleic acid metabolism, by targeting key proteins such as aspartate aminotransferase (GOT1), cytochrome P450 1A2 (CYP1A2), and carbonic anhydrase 2 (CA2). ScRNA-seq analysis indicated that HQD may enhance the functionality of cytotoxic T cells, thereby reversing the immunosuppressive microenvironment. Virtual verification revealed a strong binding affinity between the identified hub targets and active constituents of HQD, a finding subsequently corroborated by AFM assays. Cellular experiments confirmed that naringenin treatment inhibits the proliferation, migration, and invasion of CRC cells by downregulating GOT1 expression and disrupting glutamine metabolism. Conclusions: Computational prediction and in vitro validation reveal the active ingredients, potential targets, and molecular mechanisms of HQD against CRC liver metastasis, thereby providing a scientific foundation for the application of TCM in CRC treatment. Full article