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Chloroquine is a common antimalarial drug and is listed in the World Health Organization Standard List of Essential Medicines because of its safety, low cost and ease of use. Besides its antimalarial property, chloroquine also was used in anti-inflammatory and antivirus, especially in antitumor therapy. A mount of data showed that chloroquine mainly relied on autophagy inhibition to exert its antitumor effects. However, recently, more and more researches have revealed that chloroquine acts through other mechanisms that are autophagy-independent. Nevertheless, the current reviews lacked a comprehensive summary of the antitumor mechanism and combined pharmacotherapy of chloroquine. So here we focused on the antitumor properties of chloroquine, summarized the pharmacological mechanisms of antitumor progression of chloroquine dependent or independent of autophagy inhibition. Moreover, we also discussed the side effects and possible application developments of chloroquine. This review provided a more systematic and cutting-edge knowledge involved in the anti-tumor mechanisms and combined pharmacotherapy of chloroquine in hope of carrying out more in-depth exploration of chloroquine and obtaining more clinical applications.
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Antineoplásicos , Autofagia , Cloroquina , Neoplasias , Cloroquina/farmacologia , Cloroquina/uso terapêutico , Humanos , Neoplasias/tratamento farmacológico , Autofagia/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/química , Animais , Antimaláricos/farmacologia , Antimaláricos/uso terapêuticoRESUMO
Cancer is one of the most challenging diseases in the world. Recently, iron oxide nanoparticles (IONPs) are emerging materials with rapid development and high application value, and have shown great potential on tumor therapy due to their unique magnetic and biocompatible properties. However, some data hint us that IONPs were toxic to normal cells and vital organs. Thus, more data on biosafety evaluation is urgently needed. In this study, we compared the effects of silicon-coated IONPs (Si-IONPs) on two cell types: the tumor cells (Hela) and the normal cells (HEK293T, as 293 T for short), compared differences of protein composition, allocation and physical characteristics between these two cells. The major findings of our study pointed out that 293 T cells death occurred more significant than that of Hela cells after Si-IONPs treatment, and the rate and content of endocytosis of Si-IONPs in 293 T cells was more prominent than in Hela cells. Our results also showed Si-IONPs significant promoted the production of reactive oxygen species and disturbed pathways related to oxidative stress, iron homeostasis, apoptosis and ferroptosis in both two types of cells, however, Hela cells recovered from these disturbances more easily than 293 T. In conclusion, compared with Hela cells, IONPs are more likely to induce 293 T cells death and Hela cells have their own unique mechanisms to defense invaders, reminding scientists that future in vivo and in vitro studies of nanoparticles need to be cautious, and more safety data are needed for further clinical treatment.
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Alpha-enolase (ENO1), a multifunctional protein with carcinogenic properties, has emerged as a promising cancer biomarker because of its differential expression in cancer and normal cells. On the basis of this characteristic, we designed a cell-targeting peptide that specifically targets ENO1 and connected it with the drug doxorubicin (DOX) by aldehyde-amine condensation. A surface plasmon resonance (SPR) assay showed that the affinity for ENO1 was stronger (KD = 2.5 µM) for the resulting cell-targeting drug, DOX-P, than for DOX. Moreover, DOX-P exhibited acid-responsive capabilities, enabling precise release at the tumor site under the guidance of the homing peptide and alleviating DOX-induced cardiotoxicity. An efficacy experiment confirmed that, the targeting ability of DOX-P toward ENO1 demonstrated superior antitumor activity against colorectal cancer than that of DOX, while reducing its toxicity to cardiomyocytes. Furthermore, in vivo metabolic distribution results indicated low accumulation of DOX-P in nontumor sites, further validating its targeting ability. These results showed that the ENO1-targeted DOX-P peptide has great potential for application in targeted drug-delivery systems for colorectal cancer therapy.
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Antibióticos Antineoplásicos , Neoplasias Colorretais , Doxorrubicina , Sistemas de Liberação de Medicamentos , Fosfopiruvato Hidratase , Proteínas Supressoras de Tumor , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacologia , Fosfopiruvato Hidratase/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Animais , Proteínas Supressoras de Tumor/metabolismo , Humanos , Camundongos , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/administração & dosagem , Camundongos Endogâmicos BALB C , Camundongos Nus , Masculino , Linhagem Celular Tumoral , Células HCT116 , Ensaios Antitumorais Modelo de Xenoenxerto/métodos , Biomarcadores TumoraisRESUMO
Ingenol diterpenoids continue to attract the attention for their extensive biological activity and novel structural features. To further explore this type of compound as anti-tumor agent, 13-oxyingenol dodecanoate (13-OD) was prepared by a standard chemical transformation from an Euphorbia kansui extract, and 29 derivatives were synthesized through parent 13-OD. Their inhibition activities against different types of cancer were screened and some derivatives showed superior anti-non-small cell lung cancer (NSCLC) cells cytotoxic potencies than oxaliplatin. In addition, TMBIM6 was identified as a crucial cellular target of 13-OD using ABPP target angling technique, and subsequently was verified by pull down, siRNA interference, BLI and CETSA assays. With modulating the function of TMBIM6 protein by 13-OD and its derivatives, Ca2+ release function was affected, causing mitochondrial Ca2+ overload, depolarisation of membrane potential. Remarkably, 13-OD, B6, A2, and A10-2 induced mitophagy and ferroptosis. In summary, our results reveal that 13-OD, B6, A2, and A10-2 holds great potential in developing anti-tumor agents for targeting TMBIM6.
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Antineoplásicos , Benzenoacetamidas , Carcinoma Pulmonar de Células não Pequenas , Diterpenos , Ferroptose , Neoplasias Pulmonares , Piperidonas , Humanos , Lauratos , Mitofagia , Antineoplásicos/farmacologia , Diterpenos/farmacologia , Diterpenos/química , Neoplasias Pulmonares/tratamento farmacológico , Proteínas de Membrana/metabolismo , Proteínas Reguladoras de ApoptoseRESUMO
Identifying the cellular targets of bioactive small molecules within tissues has been a major concern in drug discovery and chemical biology research. Compared to cell line models, tissues consist of multiple cell types and complicated microenvironments. Therefore, elucidating the distribution and heterogeneity of targets across various cells in tissues would enhance the mechanistic understanding of drug or toxin action in real-life scenarios. Here, we present a novel multi-omics integration pipeline called Single-cell TargEt Profiling (STEP) that enables the global profiling of protein targets in mammalian tissues with single-cell resolution. This pipeline integrates single-cell transcriptome datasets with tissue-level protein target profiling using chemoproteomics. Taking well-established classic drugs such as aspirin, aristolochic acid, and cisplatin as examples, we confirmed the specificity and precision of cellular drug-target profiles and their associated molecular pathways in tissues using the STEP analysis. Our findings provide more informative insights into the action modes of bioactive molecules compared to in vitro models. Collectively, STEP represents a novel strategy for profiling cellular-specific targets and functional processes with unprecedented resolution.
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Exposure to environmentally hazardous substances is recognized as a significant risk factor for neurological associated disorders. Among these substances, polystyrene microplastics (PS-MPs), widely utilized in various consumer products, have been reported to exhibit neurotoxicity. However, the potential association of PS-MPs with abnormal anxiety behaviors, along with the underlying molecular mechanisms and key proteins involved, remains insufficiently explored. Here, we delineated the potential mechanisms of PS-MPs-induced anxiety through proteomics and molecular investigations. We characterized the PS-MPs, observed their accumulation in the brain, leading to anxiety-like behavior in mice, which is correlated with microglia activation and pro-inflammatory response. Consistent with these findings, our studies on BV2 microglia cells showed that PS-MPs activated NF-κB-mediated inflammation resulting in the upregulation of pro-inflammatory cytokines such as TNFα and IL-1ß. Of particular significance, HRAS was identified as a key factor in the PS-MPs induced pro-inflammatory response through whole proteomics analysis, and knockdown of H-ras effectively inhibited PS-MPs induced PERK-NF-κB activation and associated pro-inflammatory response in microglia cells. Collectively, our findings highlight that PS-MPs induce anxiety of mice via the activation of the HRAS-derived PERK-NF-κB pathway in microlglia. Our results contribute valuable insights into the molecular mechanisms of PS-MPs-induced anxiety, and may offer implications for addressing neurotoxicity and prevention the adverse effects of environmentally hazardous substances, including microplastics.
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NF-kappa B , Síndromes Neurotóxicas , Animais , Camundongos , Ansiedade/induzido quimicamente , Substâncias Perigosas , Microplásticos/toxicidade , Plásticos , Poliestirenos/toxicidadeRESUMO
Background: Acute kidney injury (AKI) is a syndrome, posing a substantial healthcare burden. The pathological basis of AKI is associated with inflammation and oxidative stress which cause additional damage to mitochondria. Artesunate (ATS) is a derivative of artemisinin isolated from Artemisia annua L. that is an effective treatment for malaria and favored for the prevention and treatment of kidney diseases. However, there are still challenges related to its efficacy, including poor water solubility, limited oral bioavailability and short half-life. Liposome-based nanoparticles are used for drug delivery due to their ideal biocompatibility and their ability to improve the bioavailability of specific drugs and enhance drug efficacy. Methods: In this study, a novel TPP-based natural ATS-nanoliposome, namely T-A-Ls, was applied for the treatment of AKI. ATS was encapsulated with or without triphenylphosphonium (TPP)-modified nanoliposomes. AKI was induced by cisplatin in C57BL/6J mice and a cisplatin-induced injury model was generated in HK-2 cells in vitro. Blood urea nitrogen (BUN), serum creatinine (Scr) measurements and section staining were utilized to assess renal protective effect of T-A-Ls. Inflammatory-related factors and proteins were quantified via Elisa, Immunofluorescence and Western Blot (WB). The anti-mitochondrial oxidative stress effect of T-A-Ls was determined by ROS, JC-1 and oxygen consumption rate (OCR) kits. Immunohistochemistry and WB were conducted to measure associated protein expressions. In vivo biodistribution and the concentration of T-A-Ls in kidney were also explored. Results: T-A-Ls exhibited good oxidative resistance, preferential renal uptake, mitochondrial targeting, and it ameliorated kidney injury in cisplatin-induced AKI mice. Mitochondrial dysfunction, ATP production and respiratory capacity were improved in damaged HK-2 cells; ROS content decreased while mitochondrial membrane potential recovered. T-A-Ls exerted renal protection by inhibiting inflammation and reducing oxidative stress; these effects were mediated by a downregulation in the expression of RAGE and iNOS and an upregulation in both Nrf2 and HO-1. Conclusion: T-A-Ls could improve the delivery of ATS to the kidney, offering a promising avenue to treat AKI.
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Injúria Renal Aguda , Cisplatino , Compostos Organofosforados , Animais , Camundongos , Cisplatino/toxicidade , Artesunato , Espécies Reativas de Oxigênio/metabolismo , Distribuição Tecidual , Camundongos Endogâmicos C57BL , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/prevenção & controle , Rim , Estresse Oxidativo , Mitocôndrias/metabolismo , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Sistemas de Liberação de Medicamentos/efeitos adversosRESUMO
Retraction of 'Dealcoholized muscadine wine was partially effective in preventing and treating dextran sulfate sodium-induced colitis and restoring gut dysbiosis in mice' by Hao Li et al., Food Funct., 2023, 14, 5994-6011, https://doi.org/10.1039/D3FO00047H.
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In recent years, a number of initially approved magnetic iron oxide nanoparticle (IONP)-based nano-medicines have been withdrawn due to the obscure nano-bio effects. Therefore, there is an urgent need to study the cellular effects triggered by IONPs on cells. In this study, we investigate the time-course cellular effects on the response of RAW 264.7 cells caused by Si-IONPs via pharmacological and mass spectrometry-based proteomics techniques. Our results revealed that Si-IONPs were internalized by clathrin-mediated endocytosis within 1 hour, and gradually degraded in endolysosomes over time, which might influence autophagy, oxidative stress, innate immune response, and inflammatory response after 12 hours. Our research provides a necessary assessment of Si-IONPs for further clinical treatment.
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Endocitose , Proteômica , Lisossomos/metabolismo , Endossomos , Nanopartículas Magnéticas de Óxido de FerroRESUMO
Standard Palm Oil (SPO) is widely used as a food ingredient partially due to its unique thermophysical properties. However, the American Heart Association recommends a saturated fat consumption of <5% of the caloric intake per day. The OxG Palm hybrid yields oil known as "palm oil with a higher content of oleic acid" (HOPO), with <35% SFA and >50% oleic acid. Characterizing novel high oleic oils is the starting point to find processes that can functionalize them such as oleogelation. This study compared the thermophysical properties of HOPO to SPO using Differential Scanning Calorimetry, shear rheology, polarized light microscopy, and texture analysis to characterize the differences between these oils. HOPO had a lower onset crystallization temperature (Δ7 °C) and its rheological behavior followed similar trends to SPO; however, large viscosity offsets were observed and were correlated to differences in crystallization temperatures. The maximum peak force of SPO was an order of magnitude higher than that of HOPO. Overall similar trends between the oils were observed, but differences in firmness, crystal morphology, and viscosity were not linearly correlated with the offset in crystallization temperature. This study quantified differences between these oils that will better enable industry to use HOPO in specific applications.
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Sepsis is characterized by a severe and life-threatening host immune response to polymicrobial infection accompanied by organ dysfunction. Studies on the therapeutic effect and mechanism of immunomodulatory drugs on the sepsis-induced hyperinflammatory or immunosuppression states of various immune cells remain limited. This study aimed to investigate the protective effects and underlying mechanism of artesunate (ART) on the splenic microenvironment of cecal ligation and puncture-induced sepsis model mice using single-cell RNA sequencing (scRNA-seq) and experimental validations. The scRNA-seq analysis revealed that ART inhibited the activation of pro-inflammatory macrophages recruited during sepsis. ART could restore neutrophils' chemotaxis and immune function in the septic spleen. It inhibited the activation of T regulatory cells but promoted the cytotoxic function of natural killer cells during sepsis. ART also promoted the differentiation and activity of splenic B cells in mice with sepsis. These results indicated that ART could alleviate the inflammatory and/or immunosuppressive states of various immune cells involved in sepsis to balance the immune homeostasis within the host. Overall, this study provided a comprehensive investigation of the regulatory effect of ART on the splenic microenvironment in sepsis, thus contributing to the application of ART as adjunctive therapy for the clinical treatment of sepsis.
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AIMS: We investigated the stage-specific mechanisms of partial resistance to artemisinin (ART, an antimalarial drug) in Plasmodium falciparum (P. falciparum) carrying the Kelch13 C580Y mutation. METHODS: Using fluorescence labeling and activity-based protein profiling, we systematically profile the ART activation levels in P. falciparum during the entire intra-erythrocytic developmental cycle (IDC), and determined the ART-targets profile of the ART-sensitive and -resistant strains at different stages. We retrieved and integrated datasets of single-cell transcriptomics and label-free proteomics across three IDC stages of wild-type P. falciparum. We also employed lipidomics to validate lipid metabolic reprogramming in the resistant strain. RESULTS: The activation and expression patterns of genes and proteins of ART-targets in both ART-sensitive and resistant strains varied at different stages and periods of P. falciparum development, with the late trophozoite stage harboring the largest number of ART targets. We identified and validated 36 overlapping targets, such as GAPDH, EGF-1a, and SpdSyn, during the IDC stages in both strains. We revealed the ART-insensitivity of fatty acid-associated activities in the partially resistant strain at both the early ring and early trophozoite stages. CONCLUSIONS: Our multi-omics strategies provide novel insights into the mechanisms of ART partial resistance in Kelch13 mutant P. falciparum, demonstrating the stage-specific interaction between ART and malaria parasites.
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Antimaláricos , Artemisininas , Malária Falciparum , Humanos , Plasmodium falciparum/genética , Multiômica , Resistência a Medicamentos/genética , Proteínas de Protozoários/genética , Proteínas de Protozoários/farmacologia , Proteínas de Protozoários/uso terapêutico , Artemisininas/farmacologia , Artemisininas/uso terapêutico , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Malária Falciparum/tratamento farmacológico , Malária Falciparum/parasitologia , MutaçãoRESUMO
Muscadine wine has a unique polyphenol profile consisting of anthocyanins, ellagic acids, and flavonols. This study aims to compare the prevention, treatment, and combined activity (P + T) of dealcoholized muscadine wine (DMW) on DSS-induced colitis in mice and its impact on the gut microbiome. Male C57BL/6 mice in the healthy and colitis group received an AIN-93M diet for 28 days. In the prevention, treatment, and P + T (prevention + treatment) groups, mice received an AIN-93M diet containing 2.79% (v/w) DMW on days 1-14, 15-28, and 1-28, respectively. Except for mice in the healthy group, all mice were given water with 2.5% (w/v) DSS on days 8-14 to induce colitis. DMW in all three receiving groups reduced myeloperoxidase activity, histology scores, and phosphorylation of Iκb-α in the colon. Colon shortening, serum IL-6, and colonic mRNA of TNF-α were blunted only in the P + T group. Gut permeability was reduced in the treatment and P + T groups. DMW in P + T group showed higher activity to increase microbiome evenness, modulate ß-diversity, elevate the cecal content of SCFAs, and enrich SCFA-producing bacteria, including Lactobacillaceae, Lachnospiraceae, Ruminococcaceae, and Peptococcaceae. This was accompanied by a decrease in pathogenic Burkholderiaceae in mice. This study suggests that muscadine wine has partial preventive and therapeutic effects against inflammatory bowel disease. The combination of prevention and treatment using DMW showed better activities than either prevention or treatment.
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Colite , Vitis , Vinho , Masculino , Animais , Camundongos , Sulfato de Dextrana/efeitos adversos , Antocianinas/farmacologia , Antocianinas/uso terapêutico , Disbiose/microbiologia , Camundongos Endogâmicos C57BL , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/patologia , Colo , Modelos Animais de DoençasRESUMO
Nanocarriers have therapeutic potential to facilitate drug delivery, including biological agents, small-molecule drugs, and nucleic acids. However, their efficiency is limited by several factors; among which, endosomal/lysosomal degradation after endocytosis is the most important. This review summarizes advanced strategies for overcoming endosomal/lysosomal barriers to efficient nanodrug delivery based on the perspective of cellular uptake and intracellular transport mechanisms. These strategies include promoting endosomal/lysosomal escape, using non-endocytic methods of delivery to directly cross the cell membrane to evade endosomes/lysosomes and making a detour pathway to evade endosomes/lysosomes. On the basis of the findings of this review, we proposed several promising strategies for overcoming endosomal/lysosomal barriers through the smarter and more efficient design of nanodrug delivery systems for future clinical applications.
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Objectives: In this study, we aimed to explore the impact of education in changing child health behavior in China and mediating role of information technology. Methods: The theoretical framework of this study incorporated variables including mental health literacy, health education, information technology, and health behavior. This is a quantitative study that has utilized secondary data for determining the results. Based on the cross-sectional data collection method, 778 responses were considered for structural equation modeling. Smart PLS 3 was used to validate the research hypotheses. Results: We found that health education and mental health literacy have a substantial impact on Chinese child health behavior. Furthermore, our data also revealed that the mediating role of information technology is useful for children's health behavior enhancement. Conclusions: The health behavior of children is influenced by education and information technology mediates the health education-health behavior relationship.
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Saúde da Criança , Tecnologia da Informação , Criança , Humanos , Estudos Transversais , Comportamentos Relacionados com a Saúde , ChinaRESUMO
This study aimed to investigate the effect of muscadine grape polyphenols (MGP) and muscadine wine polyphenols (MWP) on the onset and progression of arthritis in mice. Arthritis in male DBA/1J mice was induced by two intradermal injections of type II collagen. MGP or MWP (400 mg/kg) were orally gavaged to mice. MGP and MWP were found to delay the onset and reduce the severity and clinical symptoms of collagen induced arthritis (CIA) (P ≤ .05). In addition, MGP and MWP significantly reduced the plasma concentration of TNF-α, IL-6, anticollagen antibodies, and matrix metalloproteinase-3 in CIA mice. Based on nano computerized tomography (CT) and histological analysis, MGP and MWP reduced pannus formation, cartilage destruction, and bone erosion in CIA mice. Analysis of 16S ribosomal RNA revealed that arthritis in mice is associated with gut dysbiosis. MWP was more effective than MGP at alleviating such dysbiosis by shifting the microbiome composition toward the direction of healthy mice. Relative abundance of several genera of gut microbiome correlated with plasma inflammatory biomarkers and bone histology scores, suggesting they play a role in the development and progression of arthritis. This study suggests that muscadine grape or wine polyphenols can be used as a diet-based strategy to prevent and manage arthritis in humans.
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Artrite Experimental , Microbioma Gastrointestinal , Vitis , Vinho , Humanos , Masculino , Camundongos , Animais , Vinho/análise , Polifenóis/farmacologia , Polifenóis/análise , Disbiose , Camundongos Endogâmicos DBA , Artrite Experimental/tratamento farmacológico , Antioxidantes/análiseRESUMO
Intake biomarkers of cranberry juice in women can assess consumption in clinical trials. Discriminant biomarkers in urine may explain urinary tract infection (UTI) preventive activities. We hypothesized that validated and annotated discriminant metabolites in human urine could be used as intake biomarkers in building predictive multivariate models to classify cranberry consumers. Urine samples were collected from 16 healthy women aged 18 to 29 years at baseline and after 3- and 21-day consumption of cranberry or placebo juice in a double-blind, crossover study. Urine metabolomes were analyzed using ultra high-performance liquid chromatography coupled with Orbitrap mass spectrometry. Paired and unpaired multivariate analyses were used to annotate or identify discriminant metabolic features after cranberry consumption. Twenty-six discriminant metabolic features (paired analysis) and 27 (unpaired analysis) after cranberry consumption in an open-label intervention were rediscovered in the blinded study. These metabolites included exogenous (quinic acid) and endogenous ones (hippuric acid). The paired analysis showed better model fitting with partial least-square discriminant analysis models built on all metabolites than the unpaired analysis. Predictive models built on shared metabolites by the unpaired analysis were able to classify cranberry juice consumers with 84.4% to 100% correction rates, overall better than the paired analysis (50%-100%). The double-blind study validated discriminant metabolites from a previous open-label study. These urinary metabolites may be associated with the ability of cranberries to prevent UTIs and serve as potential cranberry intake biomarkers. It reveals the importance of selecting the right predictive models to classify cranberry consumers with higher than 95% correction rates.
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Infecções Urinárias , Vaccinium macrocarpon , Humanos , Feminino , Vaccinium macrocarpon/química , Estudos Cross-Over , Infecções Urinárias/prevenção & controle , Infecções Urinárias/tratamento farmacológico , Metaboloma , Extratos Vegetais , Biomarcadores/urinaRESUMO
Collagens in the human skin are susceptible to glycation due to their long half-life of about 15 years, accumulating advanced glycation end products (AGEs). The formation of AGEs and the subsequent AGE-induced collagen crosslinking are major factors for skin aging. The objective of this study was to determine the capacity of cranberry juice polyphenols (CJPs) and their fractions to inhibit collagen glycation and to break AGE-induced crosslinks in collagens. Concentrated cranberry juice was extracted to obtain the CJP, which was further fractionated into an ethyl acetate fraction, water fraction, 30% methanol (MeOH) fraction, 60% MeOH fraction, MeOH fraction, and acetone fraction. CJPs and their fractions contained different ratios of anthocyanins, procyanidins, and flavonols. All the fractions significantly inhibited collagen glycation assessed with the collagen-methylglyoxal (MGO) or collagen-dehydroascorbic acid (DHAA) assays. The ethyl acetate fraction and 60% MeOH had the lowest IC50 values in the collagen-MGO and collagen-DHAA assays. The methanol fraction (IC50 = 0.52 µg/mL) and acetone fraction (IC50 = 0.019 mg/mL) had the lowest IC50 values in the inhibition and breakage of AGE-induced collagen crosslinking, respectively. The ethyl acetate fraction significantly scavenged the highest amount of MGO and DHAA after incubation compared to the other fractions. Results suggested that procyanidins were the most effective antiglycation agent in both collagen glycation assays, followed by flavonols and anthocyanins. High-performance liquid chromatography-electrospray ionizationâtandem mass spectrometry showed that the reactions of DHAA with quercetin or epicatechin formed several adducts with unreported proposed structures. This study suggested that CJPs may be used as active ingredients in cosmetics to prevent skin collagen glycation and crosslinking and to break the formed crosslinks.
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Proantocianidinas , Vaccinium macrocarpon , Humanos , Proantocianidinas/farmacologia , Polifenóis , Vaccinium macrocarpon/química , Produtos Finais de Glicação Avançada/química , Antocianinas , Metanol , Acetona , Óxido de Magnésio , Aldeído Pirúvico/química , Colágeno/química , FlavonóisRESUMO
Berberine is widely used for the prevention of cancers and diabetes. However, the absorption rate of berberine is less than 1% in humans. The objective of this research was to determine whether emulsification improves the absorption and affects the metabolism of orally ingested berberine. Twelve healthy subjects, both men and women, received 800 mg berberine in a powder or emulsified form by vitamin E TPGS or Quillaja extract using a randomized crossover design. Blood samples were collected 12 hours after a dose. Berberine and its metabolites in plasma were analyzed with and without hydrolysis by glucuronidase and sulfatase on UHPLC-MS/MS. The area under the curve (AUC0-12 h) and peak plasma concentration (Cmax) of berberine was 6.7 nM h and 0.9 nM in participants who received berberine powder. They were increased to 12.6 nM h and 2.0 nM by TPGS emulsification and 28.0 nM h and 5.1 nM by Quillaja extract emulsification, respectively. Berberrubine and demethyleneberberine were detected as major phase-1 metabolites of berberine. The AUC0-12 of both free and total berberrubine was significantly increased by TPGS and Quillaja extract. Emulsification by Quillaja extract was more effective than TPGS to increase the plasma concentrations of free and total demethyleneberberine. However, the ratios of phase-1 metabolites and ratios of phase-2 conjugates were not affected by emulsification. Absorption increases of berberine by TPGS or Quillaja extract emulsification may lead to enhanced bioactivity in humans.
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Berberina , Quillaja , Feminino , Humanos , Masculino , Extratos Vegetais , Pós , Espectrometria de Massas em Tandem , Vitamina E , Estudos Cross-OverRESUMO
Background: Aristolochic acids (AAs), a class of carcinogenic and mutagenic natural products from Aristolochia and Asarum plants, are well-known to be responsible for inducing nephrotoxicity and urothelial carcinoma. Recently, accumulating evidence suggests that exposure to AAs could also induce hepatotoxicity and even hepatocellular carcinoma, though the mechanisms are poorly defined. Methods: Here, we aimed to dissect the underlying cellular and molecular mechanisms of aristolochic acid I (AAI)-induced hepatotoxicity by using advanced single-cell RNA sequencing (scRNA-seq) and proteomics techniques. We established the first single-cell atlas of mouse livers in response to AAI. Results: In hepatocytes, our results indicated that AAI activated NF-κB and STAT3 signaling pathways, which may contribute to the inflammatory response and apoptosis. In liver sinusoidal endothelial cells (LSECs), AAI activated multiple oxidative stress and inflammatory associated signaling pathways and induced apoptosis. Importantly, AAI induced infiltration of cytotoxic T cells and activation of proinflammatory macrophage and neutrophil cells in the liver to produce inflammatory cytokines to aggravate inflammation. Conclusions: Collectively, our study provides novel knowledge of AAs-induced molecular characteristics of hepatotoxicity at a single-cell level and suggests future treatment options for AAs associated hepatotoxicity.