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This study aimed to explore the pharmacodynamics and mechanisms of different processing methods of Ligustrum lucidum Ait. (LLA) in addressing kidney-yin deficiency (KYD). Forty-eight Sprague-Dawley rats were divided into eight groups based on their weight. The KYD model was established by intragastric administration of levothyroxine sodium. Each group was administered the corresponding treatment for 15 consecutive days. The general condition of the rats during the treatment period was observed. In addition, the levels of cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), and the ratio of cAMP to cGMP in the serum of rats from different groups were measured. Serum samples were analyzed using the ultra-performance liquid chromatography (UPLC)-Orbitrap Fusion MS technique for metabolomics analysis. Compared with the model group, the general condition of the rats in the wine-steamed L. lucidum group (WL) and salt-steamed L. lucidum group (SSL) groups showed significant improvement. The serum levels of cAMP, cGMP, and the cAMP-to-cGMP ratio tended to return to normal. Metabolic analysis identified 38 relevant biomarkers and revealed 3 major metabolic pathways: phenylalanine, tyrosine, and tryptophan biosynthesis; phenylalanine metabolism; and sphingolipid metabolism. The different processing methods of LLA demonstrated therapeutic effects on KYD in rats, likely related to the restoration of disturbed metabolism by adjusting the levels of endogenous metabolites in the kidney. The SSL demonstrated significantly superior effects compared with the other four types of LLA processed products.
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BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a prevalent chronic liver ailment that can lead to serious conditions such as cirrhosis and hepatocellular carcinoma. Hepatic Nogo-B regulates glucose and lipid metabolism, and its inhibition has been shown to be protective against metabolic syndrome. Increasing evidence suggests that imbalances in the gut microbiota (GM) and lipid metabolism disorders are significant contributors to NAFLD progression. Nevertheless, it is not yet known whether Nogo-B can affect NAFLD by influencing the gut microbiota and metabolites. Hence, the aim of the present study was to characterize this process and explore its possible underlying mechanisms. METHODS: A NAFLD model was constructed by administering a high-fat diet (HFD) to Nogo-B-/- and WT mice from the same litter, and body weight was measured weekly in each group. The glucose tolerance test (GTT) and insulin tolerance test (ITT) were performed to assess blood glucose levels. At the end of the 12-week period, samples of serum, liver, and intestinal contents were collected and used for serum biochemical marker and inflammatory factor detection; pathology evaluation; and gut microbiome and metabolomics analysis. Spearman's correlation analysis was performed to determine possible correlations between differential gut microbiota and differential serum metabolites between groups. RESULTS: Nogo-B deficiency attenuated the effects of the HFD, including weight gain, liver weight gain, impaired glucose tolerance, hepatic steatosis, elevated serum lipid biochemicals levels, and liver function. Nogo-B deficiency suppressed M1 polarization and promoted M2 polarization, thus inhibiting inflammatory responses. Furthermore, Nogo-B-/--HFD-fed mice presented increased gut microbiota richness and diversity, decreased Firmicutes/Bacteroidota (F/B) ratios, and altered serum metabolites compared with those of WT-HFD-fed mice. During analysis, several differential gut microbiota, including Lachnoclostridium, Harryflintia, Odoribacter, UCG-009, and unclassified_f_Butyricoccaceae, were screened between groups. These microbiota were found to be positively correlated with upregulated purine metabolism and bile acid metabolites in Nogo-B deficiency, while they were negatively correlated with downregulated corticosterone and tricarboxylic acid cyclic metabolites in Nogo-B deficiency. CONCLUSION: Nogo-B deficiency delayed NAFLD progression, as demonstrated by reduced hepatocellular lipid accumulation, attenuated inflammation and liver injury, and ameliorated gut microbiota dysbiosis and metabolic disorders. Importantly, Odoribacter was strongly positively correlated with ALB and taurodeoxycholic acid, suggesting that it played a considerable role in the influence of Nogo-B on the progression of NAFLD, a specific feature of NAFLD in Nogo-B-/- mice. The regulation of bile acid metabolism by the gut microbiota may be a potential target for Nogo-B deficiency to ameliorate NAFLD.
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Noni fruit is renowned for its abundance of bioactive compounds. Drying is an important method for processing functional products derived from noni. However, limited information exists on how drying methods affect the active metabolite profiles of noni fruit. This study investigated the impact of four common drying methods, including hot-air drying (HAD), vacuum freeze drying (VFD), microwave drying (MWD), and far infrared drying (FID), on the physicochemical indexes, bioactive components, and functional properties of dried noni fruit slices using targeted and untargeted metabonomics analysis. The results showed significant variations in appearance, water migration, and microstructure of dried noni fruit slices subjected to the four drying methods. VFD treatment yielded better dried noni fruit products when compared to other drying methods. The superiority of VFD treatment was due to its uniform stratification, reduced collapse, better retention of bioactive components and antioxidants, and higher enzyme inhibitory rates. These findings suggest that VFD method is ideal for obtaining premium bioactive profiles and maintaining the biological activity of noni fruit.
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Desecación , Manipulación de Alimentos , Liofilización , Frutas , Morinda , Morinda/química , Frutas/química , Frutas/metabolismo , Desecación/métodos , Manipulación de Alimentos/métodos , Antioxidantes/metabolismo , Antioxidantes/análisis , Metabolómica/métodos , Microondas , MetabolomaRESUMEN
Introduction: Fuqi Guben Gao (FQGBG) is a botanical drug formulation composed of FuZi (FZ; Aconitum carmichaelii Debeaux [Ranunculaceae; Aconiti radix cocta]), Wolfberry (Lycium barbarum L. [Solanaceae; Lycii fructus]), and Cinnamon (Neolitsea cassia (L.) Kosterm. [Lauraceae; Cinnamomi cortex]). It has been used to clinically treat nocturia caused by kidney-yang deficiency syndrome (KYDS) for over 30 years and warms kidney yang. However, the pharmacological mechanism and the safety of FQGBG in humans require further exploration and evaluation. Methods: We investigated the efficacy of FQGBG in reducing urination and improving immune organ damage in two kinds of KYDS model rats (hydrocortisone-induced model and natural aging model), and evaluated the safety of different oral FQGBG doses through pharmacokinetic (PK) parameters, metabonomics, and occurrence of adverse reactions in healthy Chinese participants in a randomized, double-blind, placebo-controlled, single ascending dose clinical trial. Forty-two participants were allocated to six cohorts with FQGBG doses of 12.5, 25, 50, 75, 100, and 125 g. The PKs of FQGBG in plasma were determined using a fully validated LC-MS/MS method. Results: FQGBG significantly and rapidly improved the symptoms of increased urination in both two KYDS model rats and significantly resisted the adrenal atrophy in hydrocortisone-induced KYDS model rats. No apparent increase in adverse events was observed with dose escalation. Major adverse drug reactions included toothache, thirst, heat sensation, gum pain, diarrhea, abdominal distension, T-wave changes, and elevated creatinine levels. The PK results showed a higher exposure level of benzoylhypaconine (BHA) than benzoylmesaconine (BMA) and a shorter half-life of BMA than BHA. Toxic diester alkaloids, aconitine, mesaconitine, and hypaconitine were below the lower quantitative limit. Drug-induced metabolite markers primarily included lysophosphatidylcholines, fatty acids, phenylalanine, and arginine metabolites; no safety-related metabolite changes were observed. Conclusion: Under the investigated dosing regimen, FQGBG was safe. The efficacy mechanism of FQGBG in treating nocturia caused by KYDS may be related to the improvement of the hypothalamus-pituitary-adrenal axis function and increased energy metabolism. Clinical Trial Registration: https://www.chictr.org.cn/showproj.html?proj=26934, identifier ChiCTR1800015840.
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Background: Breast cancer (BC) has the highest incidence rate among female malignant tumors. Adjuvant chemotherapy is commonly used to reduce micrometastasis in postoperative patients. However, monitoring the efficacy of chemotherapy in BC is a major challenge in clinical practice. In this study, 1H nuclear magnetic resonance (NMR) metabonomics was performed to explore the serum metabolic characteristics of BC patients before and after adjuvant chemotherapy. Methods: In this study, we collected serum samples from 51 healthy controls and 61 BC patients before and after chemotherapy for 1H NMR metabolomic analysis, and tested the performance of each metabolite and combination segment by the receiver operating characteristic (ROC) curves. Results: Nine metabolites, namely glutamine, citrate, creatine, glycerophosphatidylcholine/phosphatidylcholine, glycine, 1-methylhistidine, lactate, pyruvate and formate had significant changes in BC patients before chemotherapy compared with healthy controls. Lactate, pyruvate, 1-methylhistidine and formate were found to be inversely regulated by chemotherapy. ROC analysis showed that a combination of the four metabolites had good prediction for chemotherapy efficacy with area under the curve of 0.958, sensitivity of 98.36% and specificity of 91.30%. There was no significant correlation between chemotherapy-related metabolites and clinical indicators of cancer patients, indicating that they can be used to evaluate the chemotherapy efficacy of patients with different clinical indicators. Conclusions: Effectively, dynamic and non-invasive metabolic markers for the evaluation of the efficacy of chemotherapy were identified in this study.
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Ulcerative colitis (UC), an inflammatory disease affecting the colon and rectal mucosa, is characterized by chronic and heterogeneous behavior of unknown origin. The primary cause of UC is chronic inflammation, which is closely linked to the development of colorectal cancer. Sonchus arvensis L. (SAL), a plant consumed worldwide for its nutritional and medicinal properties, holds significance in this context. In this study, we employed the total flavone in SAL as a treatment for male C57BL/6 mice with UC. The cecal contents metabolic profile of C57BL/6 mice in different groups, including UC (group ML; n = 5), UC treated with aspirin (group AN; n = 5), UC treated with the total flavone in SAL (group FE; n = 5), and healthy male C57BL/6 mice (group CL; n = 5), was examined using UHPLC-Triple-TOF-MS. Through the identification of variations in key metabolites associated with UC and the exploration of their underlying biological mechanisms, our understanding of the pathological processes underlying this condition has been enhanced. This study identified a total of seventy-three metabolites that have a significant impact on UC. Notably, the composition of total flavone in SAL, a medication used for UC treatment, differs from that of aspirin due to the presence of four distinct metabolites (13,14-Dihydro-15-keto-PGE2, Prostaglandin I2 (PGI2), (20R,22R)-20,22-dihydroxycholesterol, and PS (18:1(9Z)/0:0)). These metabolites possess unique characteristics that set them apart. Moreover, the study identified a total of eleven pathways that were significantly enriched in mice with UC, including Aminoacyl-tRNA biosynthesis, Valine, leucine and isoleucine biosynthesis, Linoleic acid metabolism, PPAR signaling pathway, mTOR signaling pathway, Valine, leucine and isoleucine degradation, Lysine degradation, VEGF signaling pathway, Melanogenesis, Endocrine and other factor-regulated calcium reabsorption, and Cocaine addiction. These findings contribute to a better understanding of the metabolic variations in UC following total flavonoids of SAL therapy and provide valuable insights for the treatment of UC.Keywords: Ulcerative colitis; Total flavonoids of Sonchus arvensis L.; Key metabolites; Metabonomics; Cecal contents of male C57BL/6 mice.
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Hepatic diseases pose a significant threat to community health, impacting the quality of life and longevity of millions worldwide. Despite revolutionary advancements in treatment, liver diseases remain a pressing issue, necessitating the development of more effective therapeutic approaches. Here, we conducted a comprehensive multi-omics analysis to investigate the underlying mechanism of Swertiamarin in alleviating hepatic injuries induced by CCl4 in mice. We divided 100 Kunming mice into five groups: RC (control), RM (CCl4), RD (15â¯mg/Kg Swertiamarin), RZ (30â¯mg/Kg Swertiamarin), and RG (60â¯mg/Kg Swertiamarin). Animals in groups RD, RZ, and RG received daily Swertiamarin via gavage, while those in groups RM, RD, RZ, and RG were treated with CCl4 solution intraperitoneally every four days, nine times in total. Our findings revealed that mice in the RM group exhibited slightly lower average weights compared to other groups, along with significantly higher liver weight (p<0.0001) and liver index (p<0.0001). Pathological analysis indicated liver damage characterized by cell degeneration, inflammatory cell infiltration, and hepatic fibrosis in the CCl4-induced group. In contrast, Swertiamarin supplementation mitigated these effects, reducing denatured cells, inflammatory cells, and collagenous fibers in the liver. Serum analysis showed elevated levels of TNF-α (p<0.001), IL-6 (p<0.05), ALT (p<0.001), AST (p<0.0001), MDA (p<0.001), and Hyp (p<0.001) in CCl4-induced animals, along with lower levels of T-AOC (p<0.001), GSH-px (p<0.0001), SOD (p<0.001), and CAT (p<0.01). Microbiome analysis revealed significant differences among groups, with pathogenic taxa such as Arthrinium and Aureobasidium, and probiotic Saccharomyces showing notable variations. Metabolomics analysis identified numerous differentially abundant metabolites, with Swertiamarin-treated animals exhibiting distinct profiles. Our findings highlight the potential of Swertiamarin ameliorating CCl4-induced liver toxicity through modulation of antioxidant capacity, inflammatory response, gut microbiota, and metabolites. These insights may inform the development of novel therapies for liver injury.
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Tetracloruro de Carbono , Enfermedad Hepática Inducida por Sustancias y Drogas , Glucósidos Iridoides , Hígado , Pironas , Animales , Pironas/farmacología , Glucósidos Iridoides/farmacología , Ratones , Hígado/efectos de los fármacos , Hígado/patología , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Masculino , Metabolómica , Estrés Oxidativo/efectos de los fármacos , Multiómica , Animales no ConsanguíneosRESUMEN
Background: Untargeted metabonomics has provided new insight into the pathogenesis of sarcopenia. In this study, we explored plasma metabolic signatures linked to a heightened risk of sarcopenia in a cohort study by LC-MS-based untargeted metabonomics. Methods: In this nested case-control study from the Adult Physical Fitness and Health Cohort Study (APFHCS), we collected blood plasma samples from 30 new-onset sarcopenia subjects (mean age 73.2 ± 5.6 years) and 30 healthy controls (mean age 74.2 ± 4.6 years) matched by age, sex, BMI, lifestyle, and comorbidities. An untargeted metabolomics methodology was employed to discern the metabolomic profile alterations present in individuals exhibiting newly diagnosed sarcopenia. Results: In comparing individuals with new-onset sarcopenia to normal controls, a comprehensive analysis using liquid chromatography-mass spectrometry (LC-MS) identified a total of 62 metabolites, predominantly comprising lipids, lipid-like molecules, organic acids, and derivatives. Receiver operating characteristic (ROC) curve analysis indicated that the three metabolites hypoxanthine (AUC=0.819, 95% CI=0.711-0.927), L-2-amino-3-oxobutanoic acid (AUC=0.733, 95% CI=0.598-0.868) and PC(14:0/20:2(11Z,14Z)) (AUC= 0.717, 95% CI=0.587-0.846) had the highest areas under the curve. Then, these significant metabolites were observed to be notably enriched in four distinct metabolic pathways, namely, "purine metabolism"; "parathyroid hormone synthesis, secretion and action"; "choline metabolism in cancer"; and "tuberculosis". Conclusion: The current investigation elucidates the metabolic perturbations observed in individuals diagnosed with sarcopenia. The identified metabolites hold promise as potential biomarkers, offering avenues for exploring the underlying pathological mechanisms associated with sarcopenia.
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Metabolómica , Sarcopenia , Humanos , Sarcopenia/metabolismo , Sarcopenia/sangre , Masculino , Metabolómica/métodos , Femenino , Anciano , Estudios de Casos y Controles , Cromatografía Liquida/métodos , Biomarcadores/sangre , Estudios de Cohortes , Metaboloma , Anciano de 80 o más Años , Espectrometría de Masas/métodos , Factores de Riesgo , Hipoxantina/sangre , Hipoxantina/metabolismo , Cromatografía Líquida con Espectrometría de MasasRESUMEN
Baccaurea ramiflora Lour. is a new kind of underutilized wild fruit tree; the metabolic reasons for its fruit flavor changes are not yet clear. In this study, the pink flesh of this excellent tasting fruit (BR) was used to reveal the metabolic causes of taste variations through five developmental stages. We identified 154 common differential metabolites of different developmental stages based on non-targeted metabolomics analysis. The accumulation of sugar and fatty acids increased significantly after 73 days, while citric acid decreased significantly. Flesh color accumulation mainly occurred 53 days ago, and vitamin accumulation occurred after 93 days. Interestingly, L-sorbose and 5-hydroxyindole-3-acetic acid were positively correlated with the sugar-acid ratio but negatively correlated with titratable acids. It indicated that L-sorbose and 5-hydroxyindole-3-acetic acid may be taste biomarkers of BR B. ramiflora. The results provided new metabolic lines of evidence for the taste variation during the ripening process of B. ramiflora.
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Extraction of anthocyanins from Lycium ruthenicum Murr. (L. ruthenicum) is a notable challenge in food production, requiring methods that balance efficiency and safety. In this study, we conducted a comparative analysis the extraction of anthocyanins by natural air drying (NAD), vacuum freeze drying (VFD), hot air drying (HAD), and vacuum microwave drying (MVD) combined with ultrasonic-assisted enzymolysis extraction (UAEE). The results demonstrated that the extraction yield and antioxidant activity of anthocyanins were significantly higher in VFD. This phenomenon can be attributed to the modification of raw material's microstructure, leading to an increased extraction yield of specific anthocyanins such as Cyanidin-3-galactoside, Delphinidin chloride, Cyanidin, and Petunidin. According to the pretreatment results, the extraction process of anthocyanins was further optimized. The highest yield (3.16 g/100 g) was obtained in following conditions: 0.24 % pectinase, 48 °C, solid:liquid = 1:21, and 21 min ultrasonic time. This study improves the commercial value and potential application of L. ruthenicum in food industry.
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Antocianinas , Desecación , Lycium , Antocianinas/aislamiento & purificación , Antocianinas/química , Lycium/química , Desecación/métodos , Ondas Ultrasónicas , Fraccionamiento Químico/métodos , Antioxidantes/aislamiento & purificación , Antioxidantes/química , Poligalacturonasa , MicroondasRESUMEN
Eurotium cristatum, a unique probiotic in Fu brick tea, is widely used in food processing to enhance added values. Here, green kernel black beans (GKBBs) were solid-fermented with E. cristatum and dynamic changes in flavour, chemical composition and metabolites during fermentation were investigated. As results, E. cristatum fermentation altered aroma profiles and sensory attributes of GKBBs, especially reduced sourness. After fermentation, total polyphenolic and flavonoid contents in GKBBs were elevated, while polysaccharides, soluble proteins and short-chain fatty acids contents were decreased. E. cristatum fermentation also induced biotransformation of glycosidic isoflavones into sapogenic isoflavones. During fermentation, dynamic changes in levels of 17 amino acids were observed, in which 3 branched-chain amino acids were increased. Non-targeted metabolomics identified 51 differential compounds and 10 related metabolic pathways involved in E. cristatum fermentation of GKBBs. This study lays foundation for the development of green kernel black bean-based functional food products with E. cristatum fermentation.
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Eurotium , Fermentación , Valor Nutritivo , Gusto , Humanos , Eurotium/metabolismo , Eurotium/química , Semillas/metabolismo , Semillas/química , Semillas/microbiología , Polifenoles/metabolismo , Polifenoles/análisis , Polifenoles/química , Flavonoides/metabolismo , Flavonoides/análisis , Aminoácidos/metabolismo , Aminoácidos/análisisRESUMEN
BACKGROUND: Currently, there are many drugs available for the treatment of type 2 diabetes mellitus (T2DM), but most of them cause various side effects due to the need for long-term use. As a traditional Chinese medicine, Gegen Qinlian Decoction (GQD) has shown good efficacy and low side effects in the treatment of T2DM in both clinical and basic research. Based on relevant traditional Chinese medicine theories, dried ginger is innovatively added the formula of traditional GQD to create a modified GQD. This modification reduces the side effects of traditional GQD while exerting its therapeutic effect on T2DM. Previous studies have found that the modified GQD can regulate endoplasmic reticulum stress in the liver, inhibit hepatic gluconeogenesis, protect pancreatic islet ß cells, and control blood sugar levels by inhibiting the FXR/neuronal ceramide signaling pathway. GQD can also regulate the intestinal microbiota to achieve therapeutic and protective effects in various gastrointestinal diseases. However, there is no research exploring whether the modified GQD achieves its therapeutic mechanism for T2DM by regulating the intestinal microbiota. PURPOSE: To explore the mechanism of modified GQD in the treatment of T2DM based on multi-omics, focusing on its effect on the "intestinal flora bile acid TGR5'' axis. METHODS: The T2DM model was established using db/db mice, which were randomly divided into a model group, metformin group, high-dose GQD group, medium-dose GQD group, low-dose GQD group, while m/m mice were used as blank control. The drug intervention lasted for 12 weeks, during which the general conditions, oral glucose tolerance (OGT), blood glucose, and lipid-related indexes were recorded. Additionally, the fasting insulin (FINS), c-peptide, GLP-1 in serum, and cAMP in the ileum were measured by ELISA assay. Furthermore, the composition, abundance, and function of the intestinal microbiota were determined by macro genome sequencing, while bile acid was detected by targeted metabonomics. For histological evaluation, HE staining was used to observe the pathological changes of the ileum and pancreas, and the ultrastructure of the ileum and pancreas was observed by transmission electron microscopy. Apoptosis in the ileum tissue was detected by Tunel staining. Moreover, the mRNA and protein expressions of TGR5, PKA, CREB, PC1/3, GLP-1, and their phosphorylation levels in the ileum were detected by qPCR, immunohistochemistry, and Western blot; The expression of INS in the pancreas was also evaluated using immunohistochemistry. Finally, double immunofluorescence staining was used to detect the co-localization expression of TGR5 and GLP-1, NeuroD1, and GLP-1 in the ileum. RESULTS: The modified GQD was found to significantly reduce blood glucose, improve oral glucose tolerance, and blood lipid levels, as well as alleviate the injury of the ileum and pancreas in T2DM mice. Furthermore, modified GQD was found to effectively regulate intestinal flora, improve bile acid metabolism, activate the TRG5/cAMP/PKA/CREB signal pathway, and stimulate GLP-1 secretion. CONCLUSION: GQD can regulate the "intestinal flora-bile acid-TGR5" axis and has a therapeutic effect on T2DM in mice.
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Ácidos y Sales Biliares , Diabetes Mellitus Tipo 2 , Medicamentos Herbarios Chinos , Microbioma Gastrointestinal , Receptores Acoplados a Proteínas G , Animales , Masculino , Ratones , Ácidos y Sales Biliares/metabolismo , Glucemia/efectos de los fármacos , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Medicamentos Herbarios Chinos/farmacología , Microbioma Gastrointestinal/efectos de los fármacos , Hipoglucemiantes/farmacología , Metabolómica , Ratones Endogámicos C57BL , Receptores Acoplados a Proteínas G/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
Populus pseudo-cathayana × Populus deltoides is a crucial artificial forest tree species in Northeast China. The presence of the fall webworm (Hyphantria cunea) poses a significant threat to these poplar trees, causing substantial economic and ecological damage. This study conducted an insect-feeding experiment with fall webworm on P. pseudo-cathayana × P. deltoides, examining poplar's physiological indicators, transcriptome, and metabolome under different lengths of feeding times. Results revealed significant differences in phenylalanine ammonia-lyase activity, total phenolic content, and flavonoids at different feeding durations. Transcriptomic analysis identified numerous differentially expressed genes, including AP2/ERF, MYB, and WRKY transcription factor families exhibiting the highest expression variations. Differential metabolite analysis highlighted flavonoids and phenolic acid compounds of poplar's leaves as the most abundant in our insect-feeding experiment. Enrichment analysis revealed significant enrichment in the plant hormone signal transduction and flavonoid biosynthetic pathways. The contents of jasmonic acid and jasmonoyl-L-isoleucine increased with prolonged fall webworm feeding. Furthermore, the accumulation of dihydrokaempferol, catechin, kaempferol, and naringenin in the flavonoid biosynthesis pathway varied significantly among different samples, suggesting their crucial role in response to pest infestation. These findings provide novel insights into how poplar responds to fall webworm infestation.
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Populus , Populus/genética , Populus/metabolismo , Animales , Flavonoides/metabolismo , Escarabajos/fisiología , Escarabajos/metabolismo , Oxilipinas/metabolismo , Fenilanina Amoníaco-Liasa/metabolismo , Fenilanina Amoníaco-Liasa/genética , Ciclopentanos/metabolismo , Hojas de la Planta/metabolismo , Transcriptoma , Regulación de la Expresión Génica de las Plantas , Mariposas Nocturnas/genética , Mariposas Nocturnas/fisiología , Reguladores del Crecimiento de las Plantas/metabolismoRESUMEN
Fatigue, a common symptom in both diseased and healthy individuals, is a biological phenomenon characterized by a sense of extreme physical or mental exhaustion. To explore novel drugs and food sources of anti-fatigue, the hydroalcoholic extract of the root of Mirabilis himalaica (MH extract) is evaluated as anti-fatigue agents in this work, and clarifies that the mechanism of MH intervention in fatigue symptoms, and distribution of the anti-fatigue constituents in the plant of Mirabilis himalaica is examined. The results show that the MH extract have a significantly anti-fatigue effect via the pharmacological experiment and biochemical indicators. The network pharmacology, metabolomics, molecular docking, and pharmacology are integrated to determine that boeravinone A, B, and E are the pharmacoperones of anti-fatigue. Moreover, the compounds of boeravinone are present only in the root and not in the leaf and stem of the Mirabilis himalaica, which validates that root of Mirabilis himalaica is historically and officially utilized medicinal parts.
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Fatiga , Metabolómica , Mirabilis , Simulación del Acoplamiento Molecular , Farmacología en Red , Extractos Vegetales , Raíces de Plantas , Raíces de Plantas/química , Extractos Vegetales/farmacología , Metabolómica/métodos , Fatiga/tratamiento farmacológico , Animales , Masculino , Ratas Sprague-DawleyRESUMEN
BACKGROUND: To explore the neuroprotective mechanism of artemisinin against ischemic stroke from the perspective of NLRP3-mediated pyroptosis. METHODS: Serum metabolomics technology was used to analyze the serum samples of mice, and KEGG metabolic pathway was analyzed for the different metabolites in the samples. PIT model and OGD/R model were used to simulate ischemic stroke damage in vivo and in vitro. Hoechst 33342 staining, Annexin V-FITC/PI staining and TUNEL staining were used to detect the pyroptosis rate of cells. The contents of IL-1ß and IL-18 in PC12 cells and serum of mice were detected by ELISA. The expressions of NLRP3, ASC-1, Caspase-1 and TXNIP in PC12 cells and mouse brain tissue were detected by Western Blot. RESULTS: Serum metabolic profiles of animal models identified 234 different metabolites and 91 metabolic pathways. Compared with the Sham group and the Stroke+ART group, the KEGG pathway in the Stroke group was concentrated in the Necroptosis pathway associated with cell growth and death, and the NLRP3 inflammasome-mediated pyroptosis pathway was activated in the Necroptosis pathway after ischemic stroke. The results of in vivo and in vitro experiments showed that pretreatment with 10⯵M artemisinin reduced ROS production, decreased Δψm, reduced pyroptosis, maintained neuronal cell morphology, and down-regulated the contents of IL-1ß and IL-18 as well as the expression of key proteins of NLRP3, ASC-1, Caspase-1 and TXNIP(p<0.01). CONCLUSION: Artemisinin can reduce neuronal pyroptosis induced by ischemic stroke by inhibiting ROS/TXNIP/NLRP3/Caspase-1 signaling pathway.
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Artemisininas , Proteínas Portadoras , Caspasa 1 , Accidente Cerebrovascular Isquémico , Ratones Endogámicos C57BL , Proteína con Dominio Pirina 3 de la Familia NLR , Piroptosis , Especies Reactivas de Oxígeno , Transducción de Señal , Animales , Piroptosis/efectos de los fármacos , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Caspasa 1/metabolismo , Transducción de Señal/efectos de los fármacos , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/metabolismo , Accidente Cerebrovascular Isquémico/patología , Artemisininas/farmacología , Ratones , Proteínas Portadoras/metabolismo , Células PC12 , Especies Reactivas de Oxígeno/metabolismo , Masculino , Ratas , Proteínas de Ciclo Celular/metabolismo , Fármacos Neuroprotectores/farmacología , Inflamasomas/metabolismo , Inflamasomas/efectos de los fármacos , Modelos Animales de Enfermedad , TiorredoxinasRESUMEN
Acute alcohol intoxication is a harmful clinical condition characterized by behavioral and neurological symptoms, for which few effective therapies are available at present. Dysfunction of microglial BV-2 cells has been reported to be associated with acute alcohol-induced brain injuries. In the present study, the protective effects of Eucommia ulmoides Oliv. leaves polysaccharides (EULP) on acute alcoholic brain injury and microglial dysfunction were investigated. 14-day pretreatment of EULP significantly attenuated neurobehavioral deficit and neurotransmitter damage in the brain tissue of mice caused by acute alcohol exposure. Additionally, EULP regulated the metabolic disorder of brain tissue. Consistently, it was shown that EULP pretreatment significantly improved alcohol-induced phagocytosis decrease, oxidative stress and inflammation in BV-2 cells. Therefore, EULP may be proposed and employed as a potential therapeutic agent for alcohol-induced brain damage.
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Eucommiaceae , Microglía , Estrés Oxidativo , Hojas de la Planta , Polisacáridos , Animales , Polisacáridos/farmacología , Polisacáridos/química , Microglía/efectos de los fármacos , Microglía/metabolismo , Ratones , Eucommiaceae/química , Hojas de la Planta/química , Estrés Oxidativo/efectos de los fármacos , Masculino , Etanol , Lesiones Encefálicas/tratamiento farmacológico , Lesiones Encefálicas/inducido químicamente , Lesiones Encefálicas/metabolismo , Lesiones Encefálicas/etiología , Lesiones Encefálicas/patología , Línea Celular , Fagocitosis/efectos de los fármacos , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/patología , Extractos Vegetales/farmacología , Extractos Vegetales/químicaRESUMEN
Anemarrhena asphodeloides Bunge-Phellodendron chinense Schneid (AAPC) is one of the most widely accepted herb pairs in Chinese medicine prescription for treating benign prostatic hyperplasia (BPH). However, the mechanisms underlying the combination of the two herbs for anti-BPH are still not completely clear. To uncover the potential mechanism of the AAPC herb pair in the treatment of BPH, chemical profiling, network pharmacology, serum metabonomics and experimental validation were integrated. UHPLC-Q-Exactive Orbitrap-MS was performed to characterize the chemical profiling of the herb pair extract, and network pharmacology was employed to forecast the potential effective components, core targets and key signaling pathways. Then, western blot and RT-PCR experiments were conducted to verify the PI3K/Akt/NF-κB signaling pathway predicted by network pharmacology. Finally, the serum differential metabolites and metabolic pathways were analyzed by serum non-targeted metabonomics, and these results were jointly analyzed by MetScape. 51 chemical components of the AAPC herb pair extract were identified, including phellodendrine, magnoflorine, berberine, mangiferin, anemarsaponin BIII, etc. In network pharmacology, the predicted core targets of these components include AKT1, TNF, EGFR, PTGS2, PIK3CA, etc. The KEGG pathway enrichment analysis indicated that PI3K-Akt, Rap1 and MAPK signaling pathways may play a key role in the AAPC herb pair for the treatment of BPH, and the results of animal experiments demonstrated that the herb pair could significantly inhibit the activation and expression of p-PI3K/PI3K, p-Akt/Akt, p-NF-κB/NF-κB in protein and mRNA levels. Furthermore, 31 serum differential metabolites and three main metabolic pathways were obtained by serum non-targeted metabonomics. And the crucial metabolic pathway of arachidonic acid (AA) was obtained by integrated analysis of network pharmacology and metabonomics results. In conclusion, the AAPC herb pair can improve BPH through inhibiting the activation and expression of the PI3K/Akt/NF-κB signaling pathway and AA metabolism.
Asunto(s)
Anemarrhena , Medicamentos Herbarios Chinos , Metabolómica , Farmacología en Red , Phellodendron , Hiperplasia Prostática , Transducción de Señal , Hiperplasia Prostática/tratamiento farmacológico , Hiperplasia Prostática/sangre , Masculino , Anemarrhena/química , Metabolómica/métodos , Farmacología en Red/métodos , Phellodendron/química , Animales , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Transducción de Señal/efectos de los fármacos , Cromatografía Líquida de Alta Presión/métodos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Ratas Sprague-Dawley , FN-kappa B/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Extractos Vegetales/farmacologíaRESUMEN
In this study, the influence of the distillation system, geographical origin, and aging time on the volatiles of brandy was investigated. An untargeted metabolomics approach was used to classify the volatile profiles of brandies based on the presence of different distillation systems and geographical origins. Through the predictive ability of PLS-DA models, it was found that higher alcohols, C13-norisopenoids, and furans could serve as key markers to discriminate between continuous stills and pot stills, and the contents of C6/C9 compounds, C13-norisoprenoids, and sesquiterpenoids were significantly affected by brandy origin. A network analysis illustrated that straight-chain fatty acid ethyl esters gradually accumulated during aging, and several higher alcohols, furfural, 5-methylfurfural, 4-ethylphenol, TDN, ß-damascenone, naphthalene, styrene, and decanal were also positively correlated with aging time. This study provides effective methods for distinguishing brandies collected from different distillation systems and geographical origins and summarizes an overview of the changes in volatile compounds during the aging process.
RESUMEN
OBJECTIVES: Acute pancreatitis(AP) is a common digestive tract disease, often accompanied by severe metabolic disorders, but there are no specific markers and treatment methods, and the potential metabolic pathways behind it remain to be explored. METHODS: Establish mild acute pancreatitis and severe acute pancreatitis models in rats and intervene with antioxidant NAC. Analyze serum oxidative stress indicators and pathological changes in pancreatic tissue. In addition, non-targeted metabolomics analysis of serum differential metabolites between groups was conducted based on the LC/MS system. RESULTS: The pathological score of the model group rats increased, and the levels of oxidative stress factors ROS and MDA significantly increased, while the activity of the antioxidant enzyme SOD decreased. After NAC intervention, oxidative stress damage in rats was alleviated. Non-targeted metabolomics experiments suggest significant differences in serum metabolic profiles among different groups of rats. CONCLUSION: Metabolomics results show that the obtained differential metabolites are expected to become serum biomarkers for AP.
RESUMEN
BACKGROUND: Acupuncture is a method for treating tic disorder. However, there is a lack of sufficient clinical objective basis in regards of its treatment efficacy. Indeed, there are structural abnormalities present in energy metabolism and infrared thermography in children with tic disorder. Therefore, this study proposes a clinical trial scheme to explore the possible mechanism of acupuncture in treating tic disorder. METHODS: This randomized controlled trial will recruit a total of 90 children, in which they will be divided into non-intervention group and intervention group. The non-intervention group consists of 30 healthy children while the intervention group consists of 60 children with tic disorder. The intervention group will be randomly allocated into either the treatment group or the control group, with 30 children randomly assigned in each group. Children either received acupuncture treatment and behavioral therapy (treatment group) or sham acupuncture treatment and behavioral therapy (control group), 3 treatment sessions per week for a period of 12 weeks, with a total of 36 treatment sessions. Outcome measures include YGTSS, urinary and fecal metabolomics, infrared thermography of body surface including governor vessel. For the intervention group, these outcome measures will be collected at the baseline and 90th day prior to intervention. Whereas for the non-intervention group, outcome measures (excluding YGTSS) will be collected at the baseline. DISCUSSION: The main outcome will be to observe the changes of the severity of tic condition, the secondary outcome will be to observe the changes of structural characteristic of infrared thermography of body surface/acupoints along the governor vessel and to evaluate the changes of urinary and fecal metabolomics at the end of the treatment, so as to analyze the relationship between them and to provide further knowledge in understanding the possible mechanism of acupuncture in improving the clinical symptoms via regulating and restoring the body metabolomics network, which in future it can develop as a set of clinical guideline (diagnosis, treatment, assessment, prognosis) in treating tic disorder. ChiCTR2300075188(Chinese Clinical Trial Registry, http://www.chictr.org.cn , registered on 29 August 2023).