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This study aimed to compare the structural features and functional properties of polysaccharides from single-clove garlic (SGPs) and multiclove garlic (MGPs) and to establish their structure-function relationships. Both SGPs and MGPs were identified as fructans consisting mainly of â1)-ß-d-Fruf (2â and â6)-ß-d-Fruf (2â residues but differed in average molecular weights (6.76 and 5.40 kDa, respectively). They shared similar thermodynamic properties, X-ray diffraction patterns, and high gastrointestinal digestive stability. These two purified fructans could dose-dependently scavenge free radicals, reduce oxidized metals, and effectively alleviate metronidazole-induced oxidative stress and CuSO4-induced inflammation in zebrafish via inhibiting the overexpression of inflammation-related proteins and cytokines. SGPs showed lower free radical scavenging activity in vitro than MGPs but higher antioxidant and anti-inflammatory activities in vivo. Taken together, the molecular weight was the main structural difference between the two garlic fructans of different varieties, which is a potential reason for their differences in biological activities.
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Alho , Syzygium , Animais , Frutanos/metabolismo , Antioxidantes/farmacologia , Antioxidantes/química , Alho/química , Peixe-Zebra/metabolismo , InflamaçãoRESUMO
Phellinus linteus polysaccharides exhibit antitumor, immunomodulatory, anti-inflammatory, and antioxidant properties, mitigate insulin resistance, and enhance the diversity and abundance of gut microbiota. However, the bioactivities of P. linteus polysaccharides vary owing to the complex structure, thereby, limiting their application. Various processing strategies have been employed to modify them for improving the functional properties and yield. Herein, we compare the primary modes of extraction and purification employed to improve the yield and purity, review the structure-activity relationships, and discuss the application of P. linteus polysaccharides using nano-carriers for the encapsulation and delivery of various drugs to improve bioactivity. The limitations and future perspectives are also discussed. Exploring the bioactivity, structure-activity relationship, processing methods, and delivery routes of P. linteus polysaccharides will facilitate the development of functional foods and dietary supplements rich in P. linteus polysaccharides.
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Basidiomycota , Basidiomycota/química , Polissacarídeos/química , Relação Estrutura-Atividade , Sistemas de Liberação de MedicamentosRESUMO
Despite significant advances in medical technology and antitumour treatments, the diagnosis and treatment of tumours have undergone remarkable transformations. Noninvasive phototherapy methods, such as photodynamic therapy (PDT) and photothermal therapy (PTT), have gained significant interest in antitumour medicine. However, traditional photosensitisers or photothermal agents face challenges like immune system recognition, rapid clearance from the bloodstream, limited tumour accumulation, and phototoxicity concerns. Researchers combine photosensitisers or photothermal agents with natural cell membranes to overcome these obstacles to create a nano biomimetic therapeutic platform. When used to coat nanoparticles, red blood cells, platelets, cancer cells, macrophages, lymphocytes, and bacterial outer membranes could provide prolonged circulation, tumour targeting, immune stimulation, or antigenicity. This article covers the principles of cellular membrane biomimetic nanotechnology and phototherapy, along with recent advancements in applying nano biomimetic technology to PDT, PTT, PCT, and combined diagnosis and treatment. Furthermore, the challenges and issues of using nano biomimetic nanoparticles in phototherapy are discussed. STATEMENT OF SIGNIFICANCE: Currently, there has been significant progress in the field of cell membrane biomimetic technology. Researchers are exploring its potential application in tumor diagnosis and treatment through phototherapy. Scholars have conducted extensive research on combining cell membrane technology and phototherapy in anticancer diagnosis and treatment. This review aims to highlight the mechanisms of phototherapy and the latest advancements in single phototherapy (PTT, PDT) and combination phototherapy (PCT, PRT, and PIT), as well as diagnostic approaches. The review provides an overview of various cell membrane technologies, including RBC membranes, platelet membranes, macrophage cell membranes, tumour cell membranes, bacterial membranes, hybrid membranes, and their potential for anticancer applications under phototherapy. Lastly, the review discusses the challenges and future directions in this field.
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Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Biomimética , Fototerapia , Membrana Celular , Neoplasias/patologia , Nanopartículas/uso terapêuticoRESUMO
Conventional inorganic semiconductor nanoparticles have emerged as photothermal agents in photothermal therapy and as sonosensitizers in sonodynamic therapy. However, their weak drug-loading capabilities and the deficient techniques for multifunctional inorganic nanoparticles limit their applications. A bismuth-based gold-crowned nanocomposite (BACN) was rationally designed and successfully synthesized and could then be used to prepare nanoplatforms with excellent biocompatibilities for synergistic therapy and real-time imaging. Because of the constituent gold nanoparticles and pyridine, the nanoplatforms functioned as drug delivery vehicles, ultrasonically activated sonosensitizers, and photothermal agents. The BACNs exhibited excellent photothermal conversion efficiency (79.1%) in the second near-infrared biowindow (1064 nm). Cellular and mouse experiments demonstrated that under laser and ultrasound irradiation bufalin-loaded BACNs significantly reduced cancer cell counts and completely eradicated tumors, along with great therapeutic biosafety and no discernible recurrence. Additionally, BACNs were also used as contrast agents in computed tomography-photoacoustic imaging. The versatile BACN nanoplatform with multitreatment effects and trimodal imaging properties shows immense potential as an antitumor nanotherapeutic system.
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Nanopartículas Metálicas , Nanocompostos , Nanopartículas , Neoplasias , Animais , Camundongos , Ouro/farmacologia , Bismuto , Nanopartículas Metálicas/uso terapêutico , Fototerapia/métodos , Nanopartículas/uso terapêutico , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Nanocompostos/uso terapêutico , Linhagem Celular TumoralRESUMO
Gardenia fruit (GF) is the mature fruit of Gardenia jasminoides Ellis, boasting a rich array of nutrients and phytochemicals. Over time, GF has been extensively utilized in both food and medicinal contexts. In recent years, numerous studies have delved into the chemical constituents of GF and their associated pharmacological activities, encompassing its phytochemical composition and health-promoting properties. This review aims to provide a critical and comprehensive summary of GF research, covering nutrient content, extraction technologies, and potential health benefits, offering new avenues for future investigations and highlighting its potential as an innovative food resource. Additionally, the review proposes novel industrial applications for GF, such as utilizing gardenia yellow/red/blue pigments in the food industry and incorporating it with other herbs in traditional Chinese medicine. By addressing current challenges in developing GF-related products, this work provides insights for potential applications in the cosmetics, food, and health products industries. Notably, there is a need for the development of more efficient extraction methods to harness the nutritional components of GF fully. Further research is needed to understand the specific molecular mechanisms underlying its bioactivities. Exploring advanced processing techniques to create innovative GF-derived products will show great promise for the future.
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For quality control of Chinese patent medicines (CPMs) containing the same herbal medicine or different herbal medicines that have similar chemical composition, current â³one standard for one speciesâ³ research mode leads to poor universality of the analytical approaches unfavorable to discriminate easily confused species. Herein, we were aimed to elaborate a multiple heart-cutting two-dimensional liquid chromatography/charged aerosol detector (MHC-2DLC/CAD) approach to quantitatively assess ginseng from multiple CPMs. Targeting baseline resolution of 16 ginsenosides (noto-R1/Rg1/Re/Rf/Ra2/Rb1/Rc/Ro/Rb2/Rb3/Rd/Rh1/Rg2/Rg3/Rg3(R)/24(R)-p-F11), experiments were conducted to optimize key parameters and validate its performance. A Poroshell 120 EC-C18 column and an XBridge Shield RP18 column were separately utilized in the first-dimensional (1D) and the second-dimensional (2D) chromatography. Eight consecutive cuttings could achieve good separation of 16 ginsenosides within 85 min. The developed MHC-2DLC/CAD method showed good linearity (R2 > 0.999), repeatability (RSD < 6.73%), stability (RSD < 5.63%), inter- and intra-day precision (RSD < 5.57%), recovery (93.76-111.14%), and the limit of detection (LOD) and limit of quantification (LOQ) varied between 0.45-2.37 ng and 0.96-4.71 ng, respectively. We applied it to the content determination of 16 ginsenosides simultaneously from 28 different ginseng-containing CPMs, which unveiled the ginsenoside content difference among the tested CPMs, and gave useful information to discriminate ginseng in the preparation samples, as well. The MHC-2DLC/CAD approach exhibited advantages of high specificity, good separation ability, and relative high analysis efficiency, which also justified the feasibility of our proposed â³Monomethod Characterization of Structure Analogsâ³ strategy in quality evaluation of diverse CPMs that contained different ginseng.
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Medicamentos de Ervas Chinesas , Ginsenosídeos , Panax , Aerossóis , Cromatografia Líquida , Medicamentos sem PrescriçãoRESUMO
To accurately identify the metabolites is crucial in a number of research fields, and discovery of new compounds from the natural products can benefit the development of new drugs. However, the preferable phytochemistry or liquid chromatography/mass spectrometry approach is time-/labor-extensive or receives unconvincing identifications. Herein, we presented a strategy, by integrating offline two-dimensional liquid chromatography/ion mobility-quadrupole time-of-flight mass spectrometry (2D-LC/IM-QTOF-MS), exclusion list-containing high-definition data-dependent acquisition (HDDDA-EL), and quantitative structure-retention relationship (QSRR) prediction of the retention time (tR), to facilitate the in-depth and more reliable identification of herbal components and thus to discover new compounds more efficiently. Using the saponins in Panax quinquefolius flower (PQF) as a case, high orthogonality (0.79) in separating ginsenosides was enabled by configuring the XBridge Amide and CSH C18 columns. HDDDA-EL could improve the coverage in MS2 acquisition by 2.26 folds compared with HDDDA (2933 VS 1298). Utilizing 106 reference compounds, an accurate QSRR prediction model (R2 = 0.9985 for the training set and R2 = 0.88 for the validation set) was developed based on Gradient Boosting Machine (GBM), by which the predicted tR matching could significantly reduce the isomeric candidates identification for unknown ginsenosides. Isolation and establishment of the structures of two malonylginsenosides by NMR partially verified the practicability of the integral strategy. By these efforts, 421 ginsenosides were identified or tentatively characterized, and 284 thereof were not ever reported from the Panax species. The current strategy is thus powerful in the comprehensive metabolites characterization and rapid discovery of new compounds from the natural products.
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Produtos Biológicos , Ginsenosídeos , Panax , Ginsenosídeos/análise , Panax/química , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas/métodos , Cromatografia Líquida , Flores/química , Produtos Biológicos/análiseRESUMO
This study investigated the pharmacological and pathological effects of aqueous mulberry leaf extract on type 1 diabetes mellitus mice induced with an intraperitoneal injection of streptozotocin (STZ). Diabetic mice were randomized into six groups: control (normal group), model, metformin-treated mice, and high-dose, medium-dose, and low-dose mulberry. The mulberry-treated mice were divided into high-, medium-, and low-dose groups based on the various doses of aqueous mulberry leaf extract during gavage. The efficacy of the six-week intervention was evaluated by measuring levels of fasting plasma glucose, alkaline phosphatase, alanine aminotransferase, aspartate transaminase, blood urea nitrogen, gamma-glutamyl transferase, glucose, high-density lipoprotein cholesterol, lactate dehydrogenase, and low-density lipoprotein cholesterol and recording body weight. Results revealed that mulberry leaf extract exhibited an ideal hypoglycemic effect, and the high-dose group was the most affected. Histology analysis, glycogen staining and apoptosis detection were used to study the extract's effects on the liver, kidney, and pancreatic cells of diabetic mice, enabling the assessment of its effectiveness and complications on a clinical and theoretical basis. It was shown that a certain concentration of aqueous mulberry leaf extract repaired the islet cells of type 1 diabetes mellitus mice, promoting normal insulin secretion. Herein, it was confirmed that mulberry leaf could be used to develop new hypoglycemic drugs or functional health food with broad applicability.
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Ginseng extracts are extensively used as raw materials for food supplements and herbal medicines. This study aimed to characterize ginsenosides obtained from six Panax plant extracts (Panax ginseng, red ginseng, Panax quinquefolius, Panax notoginseng, Panax japonicus, and Panax japonicus var. major) and compared them with their in vitro metabolic profiles mediated by rat intestinal microbiota. Ultrahigh-performance liquid chromatography/ion mobility-quadrupole time-of-flight mass spectrometry (UHPLC/IM-QTOF-MS) with scheduled multiple reaction monitoring (sMRM) quantitation methods were developed to characterize and compare the ginsenoside composition of the different extracts. After in vitro incubation, 248 ginsenosides/metabolites were identified by UHPLC/IM-QTOF-MS in six biotransformed samples. Deglycosylation was determined to be the main metabolic pathway of ginsenosides, and protopanaxadiol-type and oleanolic acid-type saponins were easier to be easily metabolized. Compared with the ginsenosides in plant extracts, those remaining in six biotransformed samples were considerably fewer after biotransformation for 8 h. However, the compositional differences in four subtypes of the ginsenosides among the six Panax plants became more distinct.
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Microbioma Gastrointestinal , Ginsenosídeos , Panax notoginseng , Ratos , Animais , Ginsenosídeos/química , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas/métodos , Cromatografia Líquida , Panax notoginseng/química , Extratos Vegetais/químicaRESUMO
The aim of this study was to investigate the effect and molecular mechanism of Xuebijing Injection in the treatment of sepsis-associated acute respiratory distress syndrome(ARDS) based on network pharmacology and in vitro experiment. The active components of Xuebijing Injection were screened and the targets were predicted by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The targets of sepsis-associated ARDS were searched against GeneCards, DisGeNet, OMIM, and TTD. Weishengxin platform was used to map the targets of the main active components in Xuebijing Injection and the targets of sepsis-associated ARDS, and Venn diagram was established to identify the common targets. Cytoscape 3.9.1 was used to build the "drug-active components-common targets-disease" network. The common targets were imported into STRING for the building of the protein-protein interaction(PPI) network, which was then imported into Cytoscape 3.9.1 for visualization. DAVID 6.8 was used for Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment of the common targets, and then Weishe-ngxin platform was used for visualization of the enrichment results. The top 20 KEGG signaling pathways were selected and imported into Cytoscape 3.9.1 to establish the KEGG network. Finally, molecular docking and in vitro cell experiment were performed to verify the prediction results. A total of 115 active components and 217 targets of Xuebijing Injection and 360 targets of sepsis-associated ARDS were obtained, among which 63 common targets were shared by Xuebijing Injection and the disease. The core targets included interleukin-1 beta(IL-1ß), IL-6, albumin(ALB), serine/threonine-protein kinase(AKT1), and vascular endothelial growth factor A(VEGFA). A total of 453 GO terms were annotated, including 361 terms of biological processes(BP), 33 terms of cellular components(CC), and 59 terms of molecular functions(MF). The terms mainly involved cellular response to lipopolysaccharide, negative regulation of apoptotic process, lipopolysaccharide-mediated signaling pathway, positive regulation of transcription from RNA polyme-rase â ¡ promoter, response to hypoxia, and inflammatory response. The KEGG enrichment revealed 85 pathways. After diseases and generalized pathways were eliminated, hypoxia-inducible factor-1(HIF-1), tumor necrosis factor(TNF), nuclear factor-kappa B(NF-κB), Toll-like receptor, and NOD-like receptor signaling pathways were screened out. Molecular docking showed that the main active components of Xuebijing Injection had good binding activity with the core targets. The in vitro experiment confirmed that Xuebijing Injection suppressed the HIF-1, TNF, NF-κB, Toll-like receptor, and NOD-like receptor signaling pathways, inhibited cell apoptosis and reactive oxygen species generation, and down-regulated the expression of TNF-α, IL-1ß, and IL-6 in cells. In conclusion, Xuebijing Injection can regulate apoptosis and response to inflammation and oxidative stress by acting on HIF-1, TNF, NF-κB, Toll-like receptor, and NOD-like receptor signaling pathways to treat sepsis-associated ARDS.
Assuntos
Síndrome do Desconforto Respiratório , Sepse , Humanos , Farmacologia em Rede , Fator A de Crescimento do Endotélio Vascular , NF-kappa B , Interleucina-6 , Lipopolissacarídeos , Simulação de Acoplamento Molecular , Fator de Necrose Tumoral alfa , Sepse/complicações , Sepse/tratamento farmacológico , Sepse/genética , Proteínas NLRRESUMO
Ganoderma lucidum polysaccharides possess unique functional properties. Various processing technologies have been used to produce and modify G. lucidum polysaccharides to improve their yield and utilization. In this review, the structure and health benefits were summarized, and the factors that may affect the quality of G. lucidum polysaccharides were discussed, including the use of chemical modifications such as sulfation, carboxymethylation, and selenization. Those modifications improved the physicochemical characteristics and utilization of G. lucidum polysaccharides, and made them more stable that could be used as functional biomaterials to encapsulate active substances. Ultimate, G. lucidum polysaccharide-based nanoparticles were designed to deliver various functional ingredients to achieve better health-promoting effects. Overall, this review presents an in-depth summary of current modification strategies and offers new insights into the effective processing techniques to develop G. lucidum polysaccharide-rich functional foods or nutraceuticals.
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Ganoderma , Reishi , Reishi/química , Polissacarídeos/farmacologia , Polissacarídeos/química , Relação Estrutura-Atividade , Fenômenos Químicos , Suplementos Nutricionais , Ganoderma/químicaRESUMO
Traditional Chinese medicine (TCM) has been used for centuries to prevent and treat a variety of illnesses, and its popularity is increasing worldwide. However, the clinical applications of natural active components in TCM are hindered by the poor solubility and low bioavailability of these compounds. To address these issues, Chinese medicine self-assembly nanostrategy (CSAN) is being developed. Many active components of TCM possess self-assembly properties, allowing them to form nanoparticles (NPs) through various noncovalent forces. Self-assembled NPs (SANs) are also present in TCM decoctions, and they are closely linked to the therapeutic effects of these remedies. SAN is gaining popularity in the nano research field due to its simplicity, eco-friendliness, and enhanced biodegradability and biocompatibility compared to traditional nano preparation methods. The self-assembly of active ingredients from TCM that exhibit antitumour effects or are combined with other antitumour drugs has generated considerable interest in the field of cancer therapeutics. This paper provides a review of the principles and forms of CSAN, as well as an overview of recent reports on TCM that can be used for self-assembly. Additionally, the application of CSAN in various cancer diseases is summarized, and finally, a concluding summary and thoughts are proposed. We strongly believe that CSAN has the potential to offer fresh strategies and perspectives for the modernization of TCM.
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Protein polypeptides and polysaccharides, the indispensable macromolecular active components in traditional Chinese medicine, are widely found in Chinese medicine decoction after the decoction of traditional Chinese medicine. However, through oral administration, these macromolecules are digested by the stomach and intestine and thus fail to be absorbed in prototype. This is inconsistent with the actual clinical efficacy of Chinese medicine decoction. According to modern research, new phase structures and effects of the macromolecules emerge during the decoction of traditional Chinese medicine, but the phase change law caused by the interaction among the components of traditional Chinese medicine and the relationship between phase structure and effect are still unclear. Thus, this study reviewed the oral absorption of macromolecular components of traditional Chinese medicine, analyzed the internal relationship of the form of macromolecules in traditional Chinese medicine with the absorption and effect based on phase structure, and summarized the research mode of oral absorption and effect of macromolecules in traditional Chinese medicine with phase structures as the core, providing new ideas and methods for future research.
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Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Medicamentos de Ervas Chinesas/química , Estômago , Administração OralRESUMO
This study aimed to investigate the effective substances and mechanism of Yishen Guluo Mixture in the treatment of chronic glomerulonephritis(CGN) based on metabolomics and serum pharmacochemistry. The rat model of CGN was induced by cationic bovine serum albumin(C-BSA). After intragastric administration of Yishen Guluo Mixture, the biochemical indexes related to renal function(24-hour urinary protein, serum urea nitrogen, and creatinine) were determined, and the efficacy evaluations such as histopathological observation were carried out. The serum biomarkers of Yishen Guluo Mixture in the treatment of CGN were screened out by ultra-performance liquid chromatography-quadrupole time-of-flight/mass spectrometry(UPLC-Q-TOF-MS) combined with multivariate statistical analysis, and the metabolic pathways were analyzed. According to the mass spectrum ion fragment information and metabolic pathway, the components absorbed into the blood(prototypes and metabolites) from Yishen Guluo Mixture were identified and analyzed by using PeakView 1.2 and MetabolitePilot 2.0.4. By integrating metabolomics and serum pharmacochemistry data, a mathematical model of correlation analysis between serum biomarkers and components absorbed into blood was constructed to screen out the potential effective substances of Yishen Guluo Mixture in the treatment of CGN. Yishen Guluo mixture significantly decreased the levels of 24-hour urinary protein, serum urea nitrogen, and creatinine in rats with CGN, and improved the pathological damage of the kidney tissue. Twenty serum biomarkers of Yishen Guluo Mixture in the treatment of CGN, such as arachidonic acid and lysophosphatidylcholine, were screened out, involving arachidonic acid metabolism, glycerol phosphatide metabolism, and other pathways. Based on the serum pharmacochemistry, 8 prototype components and 20 metabolites in the serum-containing Yishen Guluo Mixture were identified. According to the metabolomics and correlation analysis of serum pharmacochemistry, 12 compounds such as genistein absorbed into the blood from Yishen Guluo Mixture were selected as the potential effective substances for the treatment of CGN. Based on metabolomics and serum pharmacochemistry, the effective substances and mechanism of Yishen Guluo Mixture in the treatment of CGN are analyzed and explained in this study, which provides a new idea for the development of innovative traditional Chinese medicine for the treatment of CGN.
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Medicamentos de Ervas Chinesas , Glomerulonefrite , Animais , Ratos , Ácido Araquidônico , Biomarcadores/sangue , Proteínas Sanguíneas , Cromatografia Líquida de Alta Pressão , Creatinina , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Glomerulonefrite/sangue , Glomerulonefrite/tratamento farmacológico , Glomerulonefrite/metabolismo , Metabolômica , Ureia , Doença Crônica , Modelos Animais de Doenças , Misturas Complexas/farmacologia , Misturas Complexas/uso terapêuticoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Yiyi Fuzi Baijiang formula (YFB) is a traditional Chinese medicine prescription composed of Coix seed, Radix Aconiti Lateralis and Patrinia villosa, which has been used to treat ulcerative colitis (UC) for thousands of years. AIM OF THE STUDY: To investigate the therapeutic effect and metabolic analysis of YFB formula on UC in rats induced by 2,4,6-trinitro-benzene sulfonic acid (TNBS). MATERIALS AND METHODS: Six main alkaloids in the YFB formula were determined by UPLCâMS/MS. The rat UC model was induced by TNBS, and the therapeutic effect of YFB formula on UC was evaluated by disease activity index (DAI) score and hematoxylin-eosin (HE) staining. UPLC-QTRAP-MS metabolomics technology was used to screen potential biomarkers for YFB treatment of UC in combination with multivariate data statistics and further analyze related metabolic pathways. Western blotting was used to detect the protein levels of NLRP1, NLRP3, NLRC4, ASC, pro-caspase1 and Caspase-1 in rat liver tissues. ELISA and immunohistochemistry were used to detect the contents of interleukin (IL)-17A, IL-21, IL-22, IL-6, TNF-α, IL-1ß and IL-18 in rat serum and liver tissues. RESULTS: The DAI scores of the YFB groups were significantly reduced, and colon tissue injury was significantly improved (p < 0.01). The results of metabolomics analysis revealed 29 potential biomarkers in serum and 27 potential biomarkers in liver. YFB formula can treat UC by affecting glycerophospholipid metabolism, primary bile acid biosynthesis, glyoxylic acid and dicarboxylic acid metabolism, and arginine and proline metabolism. Compared with the model group, the contents of IL-17A, IL-21, IL-22, IL-6, TNF-α, IL-1ß and IL-18 in the YFB groups were decreased in a dose-dependent manner (p < 0.01). Compared with those in the model group, the protein levels of NLRP1, NLRP3, NLRC4, ASC, pro-caspase1 and Caspase-1 in the YFB groups were significantly decreased in a dose-dependent manner (p < 0.01). CONCLUSIONS: The therapeutic effect of YFB formula on UC rats was dose dependent, and the effect of the YFB (2.046 g/kg) group was close to that of the positive group. YFB formula has an anti-inflammatory effect on UC by regulating the balance of Th17/Treg cells in rats.
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Colite Ulcerativa , Ratos , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Interleucina-18/efeitos adversos , Interleucina-6 , Fator de Necrose Tumoral alfa/farmacologia , Linfócitos T Reguladores , Ácido Trinitrobenzenossulfônico/toxicidade , Cromatografia Líquida , Proteína 3 que Contém Domínio de Pirina da Família NLR , Espectrometria de Massas em Tandem , Colo , Biomarcadores , Caspases , Modelos Animais de DoençasRESUMO
This study aimed to investigate the effective substances and mechanism of Yishen Guluo Mixture in the treatment of chronic glomerulonephritis(CGN) based on metabolomics and serum pharmacochemistry. The rat model of CGN was induced by cationic bovine serum albumin(C-BSA). After intragastric administration of Yishen Guluo Mixture, the biochemical indexes related to renal function(24-hour urinary protein, serum urea nitrogen, and creatinine) were determined, and the efficacy evaluations such as histopathological observation were carried out. The serum biomarkers of Yishen Guluo Mixture in the treatment of CGN were screened out by ultra-performance liquid chromatography-quadrupole time-of-flight/mass spectrometry(UPLC-Q-TOF-MS) combined with multivariate statistical analysis, and the metabolic pathways were analyzed. According to the mass spectrum ion fragment information and metabolic pathway, the components absorbed into the blood(prototypes and metabolites) from Yishen Guluo Mixture were identified and analyzed by using PeakView 1.2 and MetabolitePilot 2.0.4. By integrating metabolomics and serum pharmacochemistry data, a mathematical model of correlation analysis between serum biomarkers and components absorbed into blood was constructed to screen out the potential effective substances of Yishen Guluo Mixture in the treatment of CGN. Yishen Guluo mixture significantly decreased the levels of 24-hour urinary protein, serum urea nitrogen, and creatinine in rats with CGN, and improved the pathological damage of the kidney tissue. Twenty serum biomarkers of Yishen Guluo Mixture in the treatment of CGN, such as arachidonic acid and lysophosphatidylcholine, were screened out, involving arachidonic acid metabolism, glycerol phosphatide metabolism, and other pathways. Based on the serum pharmacochemistry, 8 prototype components and 20 metabolites in the serum-containing Yishen Guluo Mixture were identified. According to the metabolomics and correlation analysis of serum pharmacochemistry, 12 compounds such as genistein absorbed into the blood from Yishen Guluo Mixture were selected as the potential effective substances for the treatment of CGN. Based on metabolomics and serum pharmacochemistry, the effective substances and mechanism of Yishen Guluo Mixture in the treatment of CGN are analyzed and explained in this study, which provides a new idea for the development of innovative traditional Chinese medicine for the treatment of CGN.
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Animais , Ratos , Ácido Araquidônico , Biomarcadores/sangue , Proteínas Sanguíneas , Cromatografia Líquida de Alta Pressão , Creatinina , Medicamentos de Ervas Chinesas/uso terapêutico , Glomerulonefrite/metabolismo , Metabolômica , Ureia , Doença Crônica , Modelos Animais de Doenças , Misturas Complexas/uso terapêuticoRESUMO
The aim of this study was to investigate the effect and molecular mechanism of Xuebijing Injection in the treatment of sepsis-associated acute respiratory distress syndrome(ARDS) based on network pharmacology and in vitro experiment. The active components of Xuebijing Injection were screened and the targets were predicted by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The targets of sepsis-associated ARDS were searched against GeneCards, DisGeNet, OMIM, and TTD. Weishengxin platform was used to map the targets of the main active components in Xuebijing Injection and the targets of sepsis-associated ARDS, and Venn diagram was established to identify the common targets. Cytoscape 3.9.1 was used to build the "drug-active components-common targets-disease" network. The common targets were imported into STRING for the building of the protein-protein interaction(PPI) network, which was then imported into Cytoscape 3.9.1 for visualization. DAVID 6.8 was used for Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment of the common targets, and then Weishe-ngxin platform was used for visualization of the enrichment results. The top 20 KEGG signaling pathways were selected and imported into Cytoscape 3.9.1 to establish the KEGG network. Finally, molecular docking and in vitro cell experiment were performed to verify the prediction results. A total of 115 active components and 217 targets of Xuebijing Injection and 360 targets of sepsis-associated ARDS were obtained, among which 63 common targets were shared by Xuebijing Injection and the disease. The core targets included interleukin-1 beta(IL-1β), IL-6, albumin(ALB), serine/threonine-protein kinase(AKT1), and vascular endothelial growth factor A(VEGFA). A total of 453 GO terms were annotated, including 361 terms of biological processes(BP), 33 terms of cellular components(CC), and 59 terms of molecular functions(MF). The terms mainly involved cellular response to lipopolysaccharide, negative regulation of apoptotic process, lipopolysaccharide-mediated signaling pathway, positive regulation of transcription from RNA polyme-rase Ⅱ promoter, response to hypoxia, and inflammatory response. The KEGG enrichment revealed 85 pathways. After diseases and generalized pathways were eliminated, hypoxia-inducible factor-1(HIF-1), tumor necrosis factor(TNF), nuclear factor-kappa B(NF-κB), Toll-like receptor, and NOD-like receptor signaling pathways were screened out. Molecular docking showed that the main active components of Xuebijing Injection had good binding activity with the core targets. The in vitro experiment confirmed that Xuebijing Injection suppressed the HIF-1, TNF, NF-κB, Toll-like receptor, and NOD-like receptor signaling pathways, inhibited cell apoptosis and reactive oxygen species generation, and down-regulated the expression of TNF-α, IL-1β, and IL-6 in cells. In conclusion, Xuebijing Injection can regulate apoptosis and response to inflammation and oxidative stress by acting on HIF-1, TNF, NF-κB, Toll-like receptor, and NOD-like receptor signaling pathways to treat sepsis-associated ARDS.
Assuntos
Humanos , Farmacologia em Rede , Fator A de Crescimento do Endotélio Vascular , NF-kappa B , Interleucina-6 , Lipopolissacarídeos , Simulação de Acoplamento Molecular , Síndrome do Desconforto Respiratório do Recém-Nascido , Fator de Necrose Tumoral alfa , Sepse/genética , Proteínas NLRRESUMO
The antimicrobial resistance (AMR) has opened a new market for functional foods with antibacterial activities. More than ever before, people are interested in the natural foods that offer a pathogen fighting benefits due to their obvious advantages over management of diseases. Consumers who are health aware are continually using functional foods in their dietary regimens both for their nutritious, associated health benefits values and convenience. Examples include plant-based essential oils, garlic, and mushrooms. Many studies were conducted on mushrooms crude extracts as functional food with antimicrobial properties, yet the bioactive compounds isolated are few or even rare. Because antimicrobial resistance and biofilm formation are exacerbating the severity of infectious diseases worldwide, this review summarized the antimicrobial molecules compared to the number of extracts as well as the biofilm acting compounds and extracts from edible mushrooms in the last seven years to facilitate drawing the roadmap of anti-infectious agent's discovery from functional foods in the future. 156 compounds and more than 100 edible mushroom extracts with antibacterial, antifungal or biofilm inhibiting activities through the period from 2015 to 2022 were reviewed. Pubmed, Web of Science, and Scopus were thoroughly searched with relevant search words, and data reviewed indicated ninety active compounds against Gram (-ve), hundred and twenty active compounds against Gram (+ve), sixty-eight active compounds against fungi. The biofilm inhibition was revealed by nineteen compounds. Effective combinations active in biofilm inhibition were represented by quinic acid with uridine/inosine or adenine/oxalic mixtures. Activities against multi-resistant strains, represented by ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species), MRSA (Methicillin Resistant Staphylococcus aureus), VRSA (Vancomycin Resistant Staphylococcus aureus) and multi-resistant tuberculosis were shown by 39 compounds and extracts. Terpenoid compounds revealed the most potent antimicrobial action; for instance, cyathanes, cerevisterol, psathyrins and grifolaone. Because variation in cultural media is accompanied by a different response in fungal growth and mass yield as well as the variation of compounds of interest from one strain to another, the methods of isolation, cultures and media used are highlighted together with structure activity relationships when available.
Assuntos
Agaricales , Anti-Infecciosos , Alho , Staphylococcus aureus Resistente à Meticilina , Humanos , Anti-Infecciosos/farmacologia , Antibacterianos/farmacologia , BiofilmesRESUMO
This study investigated the influence of carrier oils on the in vitro and in vivo bioavailability of PTE encapsulated in scallop gonad protein isolates (SGPIs)-epigallocatechin gallate (EGCG) conjugate stabilized emulsions. The SGPIs-EGCG stabilized emulsions were subjected to an in vitro simulated digestion, and the resulting corn oil and MCT micelles were used to evaluate the PTE transportation using the Caco-2 cell model. Both emulsions remarkably improved the bioaccessibility of PTE in the micelle phase. Nevertheless, corn oil emulsions increased trans-enterocyte transportation of PTE more efficiently than MCT emulsions. Furthermore, the maximum plasma concentrations of PTE and its metabolites in mice fed with PTE emulsions were prominently higher than those in mice fed with PTE solution, while the in vivo metabolic patterns of PTE in different oil-stabilized emulsions were different. Therefore, SGPIs-EGCG stabilized emulsions could enhance the bioavailability of PTE through controlled release, in which corn oil is more suitable than MCT.
Assuntos
Micelas , Pectinidae , Animais , Disponibilidade Biológica , Células CACO-2 , Catequina/análogos & derivados , Óleo de Milho/metabolismo , Preparações de Ação Retardada/metabolismo , Emulsões/metabolismo , Excipientes/metabolismo , Gônadas/metabolismo , Humanos , Camundongos , Óleos/metabolismo , Pectinidae/metabolismo , Proteínas/metabolismo , EstilbenosRESUMO
This study investigated the potential active components against cyclooxygenase-2(COX-2) from Trachelospermi Caulisetfolium and explored the pharmacodynamic material basis.A pharmacophore-based virtual screening method was adopted to establish a COX-2 ligands-based HipHop pharmacophore model on the basis of the information on compounds with COX-2 inhibitory activity reported in published research articles.The reported components in Trachelospermi Caulisetfolium were collected to establish the compound library and matched with the pharmacophores.Subsequently, the matched small molecule compounds underwent molecular docking with COX-2 targets(PDB ID: 3 LN1), and the interaction of potential active monomers and COX-2 was further explored by molecular dynamics.The antiepileptic effect of active monomer arctigenin(15) was determined based on the pentylenetetrazole(PTZ)-induced seizure model, and its modulatory effect on the COX-2 level was evaluated.A compound library containing 118 chemical constituents in Trachelospermi Caulisetfolium was established by literature retrieval.The preferred pharmacophore 04 was selected through test set verification for virtual screening of the compound library of Trachelospermi Caulisetfolium.After matching, six potential constituents with COX-2 inhibitory activity were obtained.The interaction of five compounds with COX-2 and COX-1 was analyzed by molecular docking, and 10 ns molecular dynamics was performed on two compounds.Compound 15 could prolong the latent time of PTZ-induced seizures at medium and high doses, improve the anxiety-and depression-like behaviors induced by PTZ, reduce the expression level of COX-2, and decrease the number of COX-2 immuno-posi-tive cells in the hippocampal CA1 region.The results showed that it was reasonable to investigate the components in Trachelospermi Caulisetfolium with COX-2 inhibitory activity based on virtual screening and activity evaluation.