Search Results (1,196)

Background: Chronic alcohol intake impairs intestinal function, while L-theanine (LTA) may support intestinal health. However, the protective effects of LTA to chronic alcoholic intestinal injuries remain unclear. Methods: SD rats were administered LTA for 8 weeks and then co-administered Lieber–DeCarli liquid alcohol feed and LTA for 4 weeks to establish a chronic alcoholic intestinal injury model and investigate the mitigating influence of LTA on chronic alcoholic intestinal injury. Results: LTA alleviated duodenal pathology and intestinal permeability injury and reduced intestinal oxidative stress and inflammatory response, thereby mitigating chronic alcoholic intestinal injury. Additionally, LTA ameliorated disturbances in the gut microbiota induced by chronic alcohol intake by increasing the beneficial bacteria abundance (Ruminococcus and Odoribacter) and decreasing the harmful bacteria abundance (Enterococcus). Moreover, LTA altered the metabolic profiles associated with ethanol and linoleic (LA) and arachidonic acid (AA) metabolism. ADH6, ALDH2, and ACSS1 mRNA and protein levels were upregulated by LTA, whereas those for CYP2E1, FADS2, ALOX-5, and COX-1 were downregulated. Concurrently, LTA increased the levels of metabolites, such as acetyl-CoA, and decreased the levels of ethanol, acetaldehyde, acetic acid, LA, AA, PGE2, 13-HPODE, and LTB4. Conclusions: L-theanine mitigates chronic alcoholic intestinal injury by regulating intestinal alcohol and LA-AA metabolism. Our findings support the functional potential of the dietary supplement LTA and highlight its potential for addressing chronic intestinal injury caused by chronic alcohol intake. Full article

Thymol, a monoterpenoid phenol present in the essential oils of several aromatic plants, has attracted considerable attention for its anti-inflammatory effects, often in combination with other bioactive compounds. This work explores the mechanisms behind the anti-inflammatory activity of thymol and thymol-rich essential oils, summarizing recent experimental findings. Inflammation, a key factor in numerous chronic diseases, can be modulated by targeting essential molecular pathways, such as MAPK, NF-κB, JAK/STAT, and arachidonic acid signaling. Thymol has been shown to influence these pathways, reducing the production of pro-inflammatory cytokines and mediators. Beyond its anti-inflammatory effects, thymol also exhibits a broad range of biological activities, including antimicrobial, antioxidant, and anticancer properties. The applications of thymol and thymol-containing essential oils in therapeutic formulations, food additives, and veterinary medicine are also reviewed. Despite promising preclinical results, challenges such as low bioavailability and toxicity at high doses limit their clinical use. Recent developments in drug delivery systems, such as encapsulation in micro- and nanoparticles, are suggested as strategies to enhance efficacy. Additionally, the synergistic effects of thymol with other natural products are examined, offering the potential for improved therapeutic outcomes. Full article

The liver of fish is an essential metabolic organ that also serves an immune regulatory role. In this study, we constructed a model of largemouth bass (Micropterus salmoides) infected with Nocardia seriolae by injection to explore the immune and antioxidant functions of the liver. The results showed that N. seriolae infection caused severe pathological changes in the liver, including cell necrosis, granuloma formation, and leukocyte infiltration. The level of mRNA expression of immune-related genes in the liver was significantly increased 2 days post-infection. Moreover, the combined analysis of transcriptome and metabolome showed that N. seriolae infection markedly affected liver metabolism, including glutathione metabolism, arginine and proline metabolism, arachidonic acid metabolism, as well as starch and sucrose metabolism. Additionally, multiple key biomarkers were identified as involved in regulating responses to N. seriolae infection, including arginine, glutathione, gpx, GST, PLA2G, GAA, and PYG. To further elucidate the regulatory effects of arginine on the immune and antioxidant processes in the liver, primary hepatocytes were isolated and cultured. The results demonstrated that arginine supplementation significantly reduced the expression of LPS-induced apoptosis-related genes (bax, cas3, cas8, and cas9) by up to 50% while increasing the expression of antioxidant genes (gpx, GST) by up to 700% at 24 h. Through the analysis of metabolic changes and immune responses in the liver following N. seriolae infection, combined with in-vitro experiments, this study elucidated the anti-apoptotic and antioxidant effects of arginine, revealing the immune response mechanisms in fish liver and laying the groundwork for using nutritional strategies to improve fish health. Full article

To investigate the therapeutic impact of Forsythia suspensa extract (FS) on RSV-infected mice and explore its antiviral pharmacodynamic foundations. Methods: An integrated analytical approach, combining UPLC-Q-TOF/MS with network pharmacology, was employed to analyze and identify the chemical constituents in FS, particularly those exhibiting antiviral properties against RSV. The study integrated network pharmacology and metabolomics for further analysis, and molecular docking and interaction experiments were conducted to validate the pharmacodynamic mechanisms. Finally, an RSV pneumonia mouse model was employed to evaluate the therapeutic influence of FS, including pathological and immunohistochemistry assessments. Twenty-five components in FS were identified through UPLC-Q-TOF/MS analysis. Integrated network pharmacology data revealed 43 effective components and predicted 113 potential targets of FS for anti-RSV activity. Metabolomics analysis identified 14 metabolite biomarkers closely linked to RSV-induced metabolic disruptions involving pathways. Moreover, molecular docking and Biacore experiments provided additional confirmation that FS primarily exerts its effects through compounds such as rutin, quercetin, and kaempferol. Immunohistochemistry experiments demonstrated a significant reduction in the expression of relevant proteins following FS administration, affirming its capacity to ameliorate lung inflammation induced by RSV infection through the modulation of Toll-like receptor signaling pathways. The data presented in this study illustrate that FS exerts its anti-RSV effects by regulating the Toll-like receptor signaling pathway and the arachidonic acid metabolism pathway via rutin, quercetin, and kaempferol. Furthermore, the approach of combining network pharmacology with metabolomics proves to be an effective research strategy for investigating the bioactive constituents of medicinal plants and elucidating their pharmacological effects. Full article

Increases in flow elicit dilations in the basilar artery (BA) supplied by the posterior cerebral circulation (PCC), and ensuring efficient blood supply to the circle of Willis in which blood flow and pressure can distribute and equalize, and thus provide the appropriate supply for the daughter branches to reach certain brain areas. In contrast, increases in flow elicit constrictions in the middle cerebral artery (MCA), supplied by the anterior cerebral circulation (ACC) and regulating the blood pressure and flow in distal cerebral circulation. Mediators of flow-dependent responses include arachidonic acid (AA) metabolites and nitric oxide (NO). We hypothesized that mediators of flow-dependent responses are differentially expressed in cerebral arteries of the PCC (CA_PCC) and ACC (CA_ACC). The expressions of key enzymes of the AA pathway—cyclooxygenases (COX1/COX2), cytochrome P450 hydroxylases (Cyp450), thromboxane synthase (TXAS), thromboxane A2 (TP) receptor, prostacyclin synthase (PGIS), prostacyclin (IP) receptor (IP); neuronal nitric oxide synthase (nNOS), and endothelial nitric oxide synthase (eNOS)—in the BA and MCA from rats (n = 20) were determined by western blotting. Transcriptome analysis in CA_PCC and CA_ACC from rats (n = 25) was assessed by RNA sequencing. In BA compared to MCA, COX1/2 and Cyp450 protein expressions were lower, PGIS was higher, TXAS and nNOS/eNOS were similar, TP receptors were lower, and IP receptors were higher. Gene expressions of vasodilator canonical pathways were higher in CA_PCC; vasoconstriction canonical pathways were higher in CA_ACC. Mediators of flow-dependent vasomotor signaling are differentially expressed in cerebral arteries of the posterior and anterior circulation, corresponding to their vasomotor function. Full article

The global prevalence of asthma is approximately 4.3%, and current asthma treatments focus on reducing symptoms, maintaining normal activity levels, and preventing the deterioration of lung function, rather than achieving a cure or complete prevention. We identified isochlorogenic acid C (ICGAC) as a potential natural medicine for the treatment of asthma. However, the bioavailability of ICGAC was low, ranging from 14.4% to 16.9%, suggesting the involvement of the gut microbiota. The full spectrum of ICGAC’s anti-asthmatic mechanism remains to be elucidated. This study investigated the mechanism by which ICGAC alleviates allergic asthma through the gut–lung axis. We discovered anti-asthma pathways and targets based on the selective regulation of lipid peroxidation and employed pharmacological tools to preliminarily validate their mechanisms and efficacy. To study the role of ICGAC in regulating the gut microbiota, we performed 16S rRNA gene sequencing and metabolite analysis. Furthermore, by combining molecular biology and lipid metabolomics, we elucidated the underlying anti-asthma mechanisms of ICGAC. The effective form of ICGAC varies between single and long-term administration. The oral administration of ICGAC enhances the gut-microbiota-derived production of short-chain fatty acids (SCFAs) as the active substances, modulates immune cell activity, influences the differentiation of T- and B-cells, and reduces airway inflammation. ICGAC also regulates the metabolic network of lipid mediators (LMs) and polyunsaturated fatty acids (PUFAs), thus exerting anti-inflammatory effects by modulating arachidonate lipoxygenase (ALOX) activity and LM levels. In addition, ICGAC enhanced the antioxidant response by upregulating the expression of glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), and nuclear factor erythroid 2-related factor 2 (Nrf2), while inhibiting the release of interleukin-4 (IL-4), thereby suppressing asthma inflammation and IgE production. The anti-asthmatic mechanism of oral ICGAC involves the inhibition of lipid peroxidation by chlorogenic acid (CGA) and SCFAs produced by the gut microbiota. ICGAC suppresses asthma-associated inflammatory and oxidative stress responses through the upregulation of GPX4, SLC7A11, and Nrf2 in lung tissue. This study not only provides a solid foundation for the potential clinical use of ICGAC in asthma treatment but also offers novel insights for future research and therapeutic strategies targeting asthma. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a metabolic disease characterised by the accumulation of fat in the liver. It is estimated that 30–38% of the world’s adult population have MASLD, making it the most prevalent global chronic liver disease. Due to a lack of a therapy for MASLD, treatment has been mainly focussed on managing the conditions associated with the disease such as obesity, diabetes mellitus, and hyperlipidaemia. This study aimed to investigate the role played by Gentiana phytochemicals including the following: gentiopicroside, sweroside, and swertiamarin, in promoting hepatocyte protection against the cytotoxic effects of fatty acids. Gentiana species such as lutea, macrophylla, rigescens, and scabra are known to protect and enhance hepatocyte viability via their antioxidant, anti-inflammatory, and bitter components including the following: amarogentin gentianine, iso-orientin, swertiamarin, gentiopicroside, and sweroside. In this study, HepG2 cells pre-treated with phytochemicals gentiopicroside, sweroside, swertiamarin, and silymarin followed by an exposure to arachidonic acid (10, 30, 50 and 80 µM) were assessed for cell viability via MTT, mitochondrial function via seahorse assay, ROS levels via DCF assay, and annexin V-FITC for apoptosis. THLE-2 cells were also assayed for validation. The phytochemicals tested improved ATP production notably gentiopicroside, which improved ATP production by over 60% compared to untreated hepatocytes. Significant hepatocyte protection against lipotoxicity leading to apoptosis was also observed in gentiopicroside in the presence of 30 µM arachidonic acid with apoptosis reduced by over 50%. ROS production was reduced up to 60% by the pre-treatment of HepG2 cells with 20 µM, gentiopicroside, sweroside, swertiamarin, and silymarin, with the highest reduction observed in swertiamarin. It was concluded that phytochemicals gentiopicroside, sweroside, and swertiamarin play key roles in the hepatocyte protection against the cytotoxic effects of fatty acids. This protection is conferred by enhancing mitochondrial function in terms of increasing the maximal respiratory capacity in response to a high influx of fatty acids, promoting ATP production as well as scavenging ROS produced as a result of high fatty acid influx and increased mitochondrial respiration. Highlights: Gentiopicroside may minimise lipotoxicity leading to apoptosis and necrosis in hepatocytes in the presence of arachidonic acid. A pre-treatment of hepatocytes with phytochemicals, namely gentiopicroside, sweroside, and silymarin provides a degree of protection which may be attributed to the enhancement of mitochondrial function. Sweroside, silymarin, and swertiamarin may protect HepG2 and THLE-2 cells by scavenging ROS produced by arachidonic acid and the mitochondrial electron transport chain. Full article

Background: The growth traits of donkeys from the same farm under the same feeding conditions often vary. Methods: In this study, Plasma hormone level and LC–MS-based metabolomics was used to identify the metabolic pathways and the key metabolites associated with the growth rate of Dezhou donkeys. Results: The level of IGF-1 in the SG was significantly higher than that in the FG. The differentially abundant metabolites were related mainly to lipid metabolism, in which arachidonic acid metabolism, linoleic acid metabolism and steroid hormone biosynthesis played key roles. The main differentially abundant metabolites 2,3-dinor-8-iso-PGF2α, 11-DH-TXB2, 8(R)-HPETE, PGJ2, c9, t11-CLA, 12,13-DHOME, 9,10-DHOME, 9(10)-EpOME, 13-HPODE, DHEAS, testosterone, and corticosterone played important roles in metabolic homeostasis and affected the adaptation of donkeys to cold environments. Conclusions: The present study revealed that the growth rate of donkeys is mainly influenced by their adaptation to the environment, providing a more in-depth study on the relationship between plasma metabolomics and growth rate in donkeys. Full article

Background: Sufficient choline supply is essential for tissue functions via phosphatidylcholine and sphingomyelin within membranes and secretions like bile, lipoproteins and surfactant, and in one-carbon metabolism via betaine. Choline requirements are linked to age and genetics, folate and cobalamin via betaine, and arachidonic (ARA) and docosahexaenoic (DHA) acid transport via the phosphatidylcholine moiety of lipoproteins. Groups at risk of choline deficiency include preterm infants, children with cystic fibrosis (CF) and patients dependent on parenteral nutrition. Fortifiers, formula and supplements may differently impact their choline supply. Objective: To evaluate added amounts of choline, folate, cobalamin, ARA and DHA in fortifiers, supplements and formula used in pediatric care from product files. Methods: Nutrient contents from commonly used products, categorized by age and patient groups, were obtained from public sources. Data are shown as medians and interquartile ranges. Results: 105 nutritional products including fortifiers, formula and products for special indications were analyzed. Choline concentrations were comparable in preterm and term infant formulas (≤6 months) (31.9 [27.6–33.3] vs. 33.3 [30.8–35.2] mg/100 kcal). Products for toddlers, and patients with CF, kidney or Crohn’s disease showed Choline levels from 0 to 39 mg/100 kcal. Several products contain milk components and lecithin-based emulsifiers potentially increasing choline content beyond indicated amounts. Conclusions: Choline addition is standardized in formula for term and preterm infants up to 6 months, but not in other products. Choline content may be higher in several products due to non-declared sources. The potential impact of insufficient choline supply in patients at risk for choline deficiency suggests the need for biochemical analysis of products. Full article

The ladybird beetle, Propylea japonica Thunberg (Coleoptera: Coccinellidae), is a widely distributed natural predator that is crucial in controlling various agricultural pests in China. Despite frequent references to its remarkable thermotolerance, the molecular mechanisms underlying its thermotolerance remain poorly understood. Here, we investigated metabolomic changes in P. japonica following exposure to acute heat stress (AHS) lasting 1 h at 39 °C and 43 °C in populations from Zhengzhou (ZZ, warm temperate climate zone) and Shenzhen (SZ, subtropical climate zone), representing distinct northern and southern Chinese ecosystems. A total of 4165 and 4151 metabolites were detected in positive and negative ion modes, respectively. The high proportion of lipid and lipid-like metabolites (35.5%) and the top 20 pathways containing the highest number of metabolites, implying membrane fluidity modulation and energy metabolism restructuring, served as the core adaptive mechanism in P. japonica populations confronting thermal stress. The SZ25 vs. SZ39 exhibited a significantly higher number of differentially expressed metabolites (DEMs), which were predominantly enriched in the purine and tryptophan metabolism pathways. This indicated that these pathways orchestrate thermal adaptation in the SZ population by coordinating energy metabolism reprogramming, orchestrating antioxidant defense mechanisms, and modulating neuroendocrine homeostasis dysregulation. Additionally, the starch and sucrose, arachidonic acid, and fructose and mannose metabolism pathways were also implicated. This study enhances our understanding of P. japonica thermotolerance and provides a valuable reference for thermotolerance mechanisms in other insects. Full article

Dihydroartemisinin (DHA) is a bioactive phytopharmaceutical with diverse pharmacological potential, predominantly because of its established antiplasmodial efficacy. Here, we investigated the effects of DHA on metabolic homeostasis in Madin-Darby bovine kidney cells in the context of dose-specific adaptation of metabolism and regulation of biochemistry pathway changes. According to our findings, extensive changes in metabolism were revealed by PCA, accounting for a variability of 59.4% to distinguish contrasting metabolic signatures from normal cells. Metabolomic characterization demonstrated 67 constituting metabolites of baseline cellular processes, while 32 and 44 metabolites have demonstrated differential abundance in low- and high-dose treatments, respectively. Impaired metabolism of glycerophospholipid, amino acid, and nucleotide biosynthesis was reported with implications such as regulation of membrane reorganization, nitrogen metabolism, and cellular bioenergetics. Bioindicators of high-volume lysophosphatidylcholine (18:0) and choline phosphate revealed a lipid homeostatic change, in addition to imbalances in glutamic acid and proline levels. Pathway regulation further modulated ABC transporters and arachidonic acid signaling as implications of systemic phytopharmaceutical-modulated reorganization of metabolism. Hence, the study gives mechanistic insight into DHA-initiated modulation of cellular metabolism in MDBK cells, elucidating its status as a cellular metabolism regulator. Findings confirm the potential of DHA as a phytopharmaceutical in modulating diseases of metabolism, further solidifying its relevance in evidence-based traditional herbal remedies and natural compound therapeutics. Full article

Pyropia haitanensis (T.J. Chang and B.F. Zheng) undergoes periodic dehydration and rehydration cycles, necessitating robust adaptive mechanisms. Despite extensive research on its physiological responses to desiccation stress, the comprehensive metabolic pathways and recovery mechanisms post-rehydration remain poorly understood. This study investigated the metabolic responses of P. haitanensis to varying degrees of desiccation stress using LC-MS and UPLC-MS/MS. Under mild dehydration, the thallus primarily accumulated sugars and proline, while moderate and severe dehydration triggered the accumulation of additional osmoprotectants like alanine betaine and trehalose to maintain turgor pressure and water retention. Concurrently, the alga activated a potent antioxidant system, including enzymes and non-enzymatic antioxidants, to counteract the increased reactive oxygen species levels and prevent oxidative damage. Hormonal regulation also plays a crucial role in stress adaptation, with salicylic acid and jasmonic acid upregulating under mild dehydration and cytokinins and gibberellin GA₁₅ accumulating under severe stress. Rehydration triggered the recovery process, with indole acetic acid, abscisic acid, and jasmonic acid promoting rapid cell recovery. Additionally, arachidonic acid, acting as a signaling molecule, induced general stress resistance, facilitating the adaptation of the thallus to the dynamic intertidal environment. These findings reveal P. haitanensis’ metabolic adaptation strategies in intertidal environments, with implications for enhancing cultivation and stress resistance in this economically important seaweed. Full article

Chinese native pig breeds exhibit unique advantages over Western pig breeds, but the specific lipid metabolism mechanisms remain unclear. The phenotypic characteristics of Mashen (MS) pigs and Duroc × (Landrace × Yorkshire) (DLY) pigs are studied. The results show that MS pigs exhibit higher intramuscular fat (IMF) content. The area of adipocytes of MS pigs is significantly greater than that in DLY pigs (p < 0.01). Lipidomics analysis reveals distinct profiles in the upper layer of backfat (ULB), leaf lard (LL), greater omentum (GOM), and IMF, with MS pigs showing higher polyunsaturated fatty acids (PUFAs) in ULB, LL, and GOM. Key differential lipids identified in the two pig breeds include the following triglycerides (TGs) and phosphatidylcholines (PC): TG(16:1_18:1_18:3), TG(18:1_18:2_18:3), TG(18:3_18:2_18:2), PC(18:0_18:1), and PC(18:0_18:2). Weighted gene co-expression network analysis (WGCNA) reveals lipid molecules associated with serum biochemical indices. Transcriptomics analysis highlights 1944 differentially expressed genes between the MS-ULB and DLY-ULB. Notably, multiple genes from the cytochrome P450 family (CYP2E1, CYP4A24, CYP2J2), along with PLA2G2D, PLA2G4A, and multiple PCs, are associated with the metabolism of arachidonic acids and linoleic acids. PLA2G2D and PLA2G4A are also involved in the metabolism of α-linolenic acids. This comprehensive analysis provides essential information for breeding strategies and meat quality improvement. Full article

As a phytotherapeutic agent with historical applications in epilepsy management, Acorus tatarinowii Schott (ATS) remains pharmacologically enigmatic, particularly regarding its pathophysiological mechanisms. This knowledge gap significantly hinders the clinical application of ATS-based treatments. To explore the potential of ATS in combating epileptogenesis, we utilized a pentylenetetrazole (PTZ)-induced chronic epilepsy rat model. Brain metabolomic analysis was performed by ultra-performance liquid chromatography coupled with mass spectrometry (UPLC/MS). Principal component analysis (PCA) and orthogonal projections to latent structures-discriminant analysis (OPLS-DA) were performed for screening differential metabolites. Gut microbiota composition was analyzed through 16S rRNA gene sequencing and examined using Spearman correlation analysis. The results show that oral ATS (50 mg/kg) significantly improved the seizure latency and pathology of rats with epilepsy. Ascorbate and aldarate metabolism, glycerophospholipid metabolism, arachidonic acid metabolism, and intestinal flora were crucial for ATS’s ability to counteract epilepsy. The therapeutic effects of ATS against epilepsy were investigated with brain metabolomics and gut microbiota analysis, providing the basis for further comprehensive research. Full article

Inhibitors of cytosolic phospholipase A₂ (GIVA cPLA₂) have received great attention, since this enzyme is involved in a number of inflammatory diseases, including cancer and auto-immune and neurodegenerative diseases. Traditionally, the effects of GIVA cPLA₂ inhibitors in cells have been studied by determining the inhibition of arachidonic acid release. However, although to a lesser extent, GIVA cPLA₂ may also hydrolyze glycerophospholipids, releasing other free fatty acids (FFAs), such as linoleic acid or oleic acid. In the present work, we applied a liquid chromatography–high-resolution mass spectrometry method to study the levels of intracellular FFAs, after treating cells with selected GIVA cPLA₂ inhibitors. Six inhibitors belonging to different chemical classes were studied, using SH-SY5Y neuroblastoma cells as a model. This lipidomic approach revealed that treatment with each inhibitor created a distinct intracellular FFA profile, suggesting not only inhibitory potency against GIVA cPLA₂, but also other parameters affecting the outcome. Potent inhibitors were found to reduce not only arachidonic acid, but also other long-chain FAs, such as adrenic or linoleic acid, even medium-chain FAs, such as caproic or caprylic acid, suggesting that GIVA cPLA₂ inhibitors may affect FA metabolic pathways in general. The downregulation of intracellular FFAs may have implications in reprogramming FA metabolism in neurodegenerative diseases and cancer. Full article