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1.
Chem Rev ; 123(11): 7119-7192, 2023 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-36749705

RESUMO

Since severe global warming and related climate issues have been caused by the extensive utilization of fossil fuels, the vigorous development of renewable resources is needed, and transformation into stable chemical energy is required to overcome the detriment of their fluctuations as energy sources. As an environmentally friendly and efficient energy carrier, hydrogen can be employed in various industries and produced directly by renewable energy (called green hydrogen). Nevertheless, large-scale green hydrogen production by water electrolysis is prohibited by its uncompetitive cost caused by a high specific energy demand and electricity expenses, which can be overcome by enhancing the corresponding thermodynamics and kinetics at elevated working temperatures. In the present review, the effects of temperature variation are primarily introduced from the perspective of electrolysis cells. Following an increasing order of working temperature, multidimensional evaluations considering materials and structures, performance, degradation mechanisms and mitigation strategies as well as electrolysis in stacks and systems are presented based on elevated temperature alkaline electrolysis cells and polymer electrolyte membrane electrolysis cells (ET-AECs and ET-PEMECs), elevated temperature ionic conductors (ET-ICs), protonic ceramic electrolysis cells (PCECs) and solid oxide electrolysis cells (SOECs).

2.
Pharm Res ; 41(6): 1201-1216, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38834905

RESUMO

BACKGROUND: Some glucoside drugs can be transported via intestinal glucose transporters (IGTs), and the presence of carbohydrate excipients in pharmaceutical formulations may influence the absorption of them. This study, using gastrodin as probe drug, aimed to explore the effects of fructose, lactose, and arabic gum on intestinal drug absorption mediated by the glucose transport pathway. METHODS: The influence of fructose, lactose, and arabic gum on gastrodin absorption was assessed via pharmacokinetic experiments and single-pass intestinal perfusion. The expression of sodium-dependent glucose transporter 1 (SGLT1) and sodium-independent glucose transporter 2 (GLUT2) was quantified via RT‒qPCR and western blotting. Alterations in rat intestinal permeability were evaluated through H&E staining, RT‒qPCR, and immunohistochemistry. RESULTS: Fructose reduced the area under the curve (AUC) and peak concentration (Cmax) of gastrodin by 42.7% and 63.71%, respectively (P < 0.05), and decreased the effective permeability coefficient (Peff) in the duodenum and jejunum by 58.1% and 49.2%, respectively (P < 0.05). SGLT1 and GLUT2 expression and intestinal permeability remained unchanged. Lactose enhanced the AUC and Cmax of gastrodin by 31.5% and 65.8%, respectively (P < 0.05), and increased the Peff in the duodenum and jejunum by 33.7% and 26.1%, respectively (P < 0.05). SGLT1 and GLUT2 levels did not significantly differ, intestinal permeability increased. Arabic gum had no notable effect on pharmacokinetic parameters, SGLT1 or GLUT2 expression, or intestinal permeability. CONCLUSION: Fructose, lactose, and arabic gum differentially affect intestinal drug absorption through the glucose transport pathway. Fructose competitively inhibited drug absorption, while lactose may enhance absorption by increasing intestinal permeability. Arabic gum had no significant influence.


Assuntos
Álcoois Benzílicos , Excipientes , Frutose , Transportador de Glucose Tipo 2 , Glucose , Glucosídeos , Goma Arábica , Absorção Intestinal , Lactose , Ratos Sprague-Dawley , Transportador 1 de Glucose-Sódio , Animais , Absorção Intestinal/efeitos dos fármacos , Glucosídeos/farmacologia , Glucosídeos/administração & dosagem , Glucosídeos/farmacocinética , Transportador 1 de Glucose-Sódio/metabolismo , Transportador 1 de Glucose-Sódio/genética , Masculino , Transportador de Glucose Tipo 2/metabolismo , Transportador de Glucose Tipo 2/genética , Ratos , Excipientes/química , Excipientes/farmacologia , Glucose/metabolismo , Lactose/química , Álcoois Benzílicos/farmacologia , Álcoois Benzílicos/farmacocinética , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Transporte Biológico/efeitos dos fármacos , Permeabilidade/efeitos dos fármacos
3.
J Adolesc ; 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38375869

RESUMO

INTRODUCTION: Left-behind children are a special group that needs urgent attention. Due to enduring separation from their parents, loneliness is considered the most common and prevalent developmental hurdle in the experiences of left-behind children. This longitudinal cross-lagged study examined the direction of the association between loneliness and both internalizing and externalizing symptoms, with considering gender and left-behind status differences. METHODS: A total of 1175 rural Chinese children (48.3% boys, 39.9% left-behind children, Mage = 14.54 ± 1.18 at baseline) completed self-reported loneliness, social anxiety, and mobile phone addiction at two-time points with 6 months intervals. Descriptive statistics, cross-lagged panel analysis, and multiple group analysis were estimated in the present study. RESULTS: Loneliness exacerbated social anxiety and mobile phone addiction, and vice versa. In addition, gender and left-behind status moderated these relationships, with boys more likely to be mobile phone addicted due to loneliness and girls more likely to be lonely due to mobile phone addiction. More importantly, left-behind children with loneliness are more prone to social anxiety and mobile phone addiction, and vice versa, compared with non-left-behind children. CONCLUSIONS: The targeted interventions should be carried out for different genders and left-behind statuses. Particularly for left-behind children, neglecting to address both the symptoms of loneliness and both social anxiety and mobile phone addiction could significantly undermine the efficacy of intervention programs that solely target either one of these afflictions.

4.
J Sci Food Agric ; 2024 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-38523062

RESUMO

BACKGROUND: The microbial community plays a crucial role in Chinese strong-flavor baijiu (SFB) fermentation. However, the seasonal dynamics of the microbial community in the SFB fermentation system and its contribution to the unique flavor of SFB have not been fully elucidated. In this study, we investigated the seasonal dynamics of the microbial community through 16S rRNA and ITS gene sequencing. RESULTS: The results revealed significant temporal dynamics of microbial communities and environmental variables throughout the four seasons. The influence of seasons on fungal communities was found to be more significant than on bacterial communities. The diversity of bacteria was higher during the winter and summer, whereas fungal diversity was more prominent in summer and autumn. Stochastic processes maintained their dominance in microbial assembly throughout all four seasons but the significance of heterogeneous selection increased during summer for both bacteria and fungi, whereas homogeneous selection became more pronounced during winter for fungi. The pH and environmental temperature were important drivers of microbial community assembly across different seasons, primarily impacting the core genera responsible for the production of major volatile flavor compounds (VFCs), especially ethyl caproate. CONCLUSION: These findings provide new insights into the impact of seasons on microbial communities and hold promise for improving the quality-control measures for SFB brewed in different seasons. © 2024 Society of Chemical Industry.

5.
Photosynth Res ; 2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-38108929

RESUMO

The quality of light is an important abiotic factor that affects the growth and development of green plants. Ultraviolet, red, blue, and far-red light all have demonstrated roles in regulating green plant growth and development, as well as light morphogenesis. However, the mechanism underlying photosynthetic organism responses to green light throughout the life of them are not clear. In this study, we exposed the unicellular green alga Chlamydomonas reinhardtii to green light and analyzed the dynamics of transcriptome changes. Based on the whole transcriptome data from C. reinhardtii, a total of 9974 differentially expressed genes (DEGs) were identified under green light. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that these DEGs were mainly related to "carboxylic acid metabolic process," "enzyme activity," "carbon metabolism," and "photosynthesis and other processes." At the same time, 253 differentially expressed long non-coding RNAs (DELs) were characterized as green light responsive. We also made a detailed analysis of the responses of photosynthesis- and pigment synthesis-related genes in C. reinhardtii to green light and found that these genes exhibited obvious dynamic expression. Lastly, we constructed a co-expression regulatory network, comprising 49 long non-coding RNAs (lncRNAs) and 20 photosynthesis and pigment related genes, of which 9 mRNAs were also the predicted trans/cis-targets of 8 lncRNAs, these results suggested that lncRNAs may affect the expression of mRNAs related to photosynthesis and pigment synthesis. Our findings give a preliminary explanation of the response mechanism of C. reinhardtii to green light at the transcriptional level.

6.
Molecules ; 28(23)2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-38067420

RESUMO

Asperulosidic acid is a bioactive iridoid isolated from Hedyotis diffusa Willd. with anti-inflammatory and renal protective effects. However, its mechanism on renal interstitial fibrosis has not been elucidated yet. The present study aims to explore whether asperulosidic acid could retard renal fibrosis by reducing the circulating indoxyl sulfate (IS), which is a uremic toxin and accelerates chronic kidney disease progression by inducing renal fibrosis. In this paper, a unilateral ureteral obstruction (UUO) model of Balb/C mice was established. After the mice were orally administered with asperulosidic acid (14 and 28 mg/kg) for two weeks, blood, liver and kidney were collected for biochemical, histological, qPCR and Western blot analyses. Asperulosidic acid administration markedly reduced the serum IS level and significantly alleviated the histological changes in glomerular sclerosis and renal interstitial fibrosis. It is noteworthy that the mRNA and protein levels of the organic anion transporter 1 (OAT1), OAT3 and hepatocyte nuclear factor 1α (HNF1α) in the kidney were significantly increased, while the mRNA expressions of cytochrome P450 2e1 (Cyp2e1) and sulfotransferase 1a1 (Sult1a1) in the liver were not altered after asperulosidic acid administration. These results reveal that asperulosidic acid could accelerate the renal excretion of IS by up-regulating OATs via HNF1α in UUO mice, thereby alleviating renal fibrosis, but did not significantly affect its production in the liver, which might provide important information for the development of asperulosidic acid.


Assuntos
Nefropatias , Transportadores de Ânions Orgânicos , Insuficiência Renal Crônica , Obstrução Ureteral , Camundongos , Animais , Obstrução Ureteral/tratamento farmacológico , Obstrução Ureteral/metabolismo , Obstrução Ureteral/patologia , Indicã/metabolismo , Transportadores de Ânions Orgânicos/metabolismo , Nefropatias/tratamento farmacológico , Nefropatias/etiologia , Nefropatias/metabolismo , Rim , Insuficiência Renal Crônica/metabolismo , Fibrose , RNA Mensageiro/metabolismo
7.
Biochem Biophys Res Commun ; 632: 24-31, 2022 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-36191374

RESUMO

Postpartum depression (PPD) is a serious mental health concern of new mothers worldwide. In view of the particularity of puerpera, the research on pathogenesis and drug development of PPD are highly dependent on animal models. Although both maternal separation (MS) and chronic unpredictable mild stress (CUMS) modeling approaches have been used in PPD studies, the characteristics of the two rodent models have not been compared to explain which is more advantageous in PPD research. In this study, we applied 21-day MS and CUMS paradigms to induce mouse model of PPD and compared their differences in behavior, physiology and gut microbiota. As a result, the two models exhibited significant increases of immobility time in forced swim test (FST) and tail suspension test (TST), whereas sucrose preference index and pup weight were significantly decreased. Both displayed depression-like behaviors, and CUMS was more obvious, which demonstrated by the lower levels of 5-hydroxytryptamine (5-HT) and higher hypothalamic-pituitary-adrenal (HPA) axis related mRNA expression (corticotropin releasing hormone, corticotropin releasing hormone receptor 1) in CMUS group than that in MS group. The gut microbiota in MS and CUMS groups were significantly different in terms of the relative abundances of Bacteroidetes, Firmicutes, Proteobacteria. In conclusion, MS model and CUMS model have different performance in behavior and physiology. The CUMS model showed more obvious parameter changes, which may be more suitable for PPD induced by various social environmental factors.


Assuntos
Depressão Pós-Parto , Privação Materna , Serotonina , Animais , Feminino , Camundongos , Antidepressivos/farmacologia , Hormônio Liberador da Corticotropina/genética , Hormônio Liberador da Corticotropina/metabolismo , Depressão/metabolismo , Depressão Pós-Parto/etiologia , Receptores de Hormônio Liberador da Corticotropina , RNA Mensageiro , Serotonina/metabolismo , Estresse Psicológico/metabolismo , Sacarose , Modelos Animais de Doenças
8.
J Cardiovasc Pharmacol ; 80(3): 476-488, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35881903

RESUMO

ABSTRACT: Atherosclerosis is the primary cause of many cardiovascular diseases, and an increasing number of studies have shown that berberine could delay plaque formation and development. Therefore, we aimed to evaluate its effects and explore its mechanisms in this meta-analysis. We searched PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang, and VIP databases for original preclinical studies to conduct meta-analysis. Twelve articles (16 studies; 312 ApoE -/- mice) were included, and all the studies scored 3-5 points according to SYRCLE's risk of bias tool. Berberine could significantly decrease plaque area and plaque macrophage content (plaque area, SMD = -2.02, 95% CI: -2.80 to -1.24, P = 0.000; plaque macrophage content, SMD = -4.28, 95% CI: -7.67 to -0.88, P = 0.013); lower the levels of TC, triglyceride, and low-density lipoprotein (TC, SMD = -1.47, 95% CI: -2.20 to -0.74, P = 0.000; triglyceride, SMD = -0.77, 95% CI: -1.21 to -0.33, P = 0.000; low-density lipoprotein, SMD = -0.61, 95% CI: -1.11 to -0.11, P = 0.000), and change the secretion of inflammatory cytokines (IL-1ß, SMD = -2.29, 95% CI: -3.40 to -1.18, P = 0.000; interleukin-6, SMD = -1.48, 95% CI: -2.11 to -0.85, P = 0.008; tumor necrosis factor-α, SMD = -1.98, 95% CI: -3.01 to -0.94, P = 0.000; interleukin-10, SMD = 1.78, 95% CI: 0.76 to 2.80, P = 0.015), but there were no significant differences in high-density lipoprotein levels and plaque lipid content (high-density lipoprotein, SMD = 0.02, 95% CI: -0.35 to 0.40, P = 0.021; plaque lipid content, SMD = -6.85, 95% CI: -21.09 to 7.39, P = 0.007). The results were robust across a range of sensitivity analyses. Therefore, the results indicate that berberine is a promising drug for the treatment of atherosclerosis through regulating lipid metabolism, inflammation, and plaque composition. However, some potential mechanisms remain to be further elucidated.


Assuntos
Aterosclerose , Berberina , Animais , Aterosclerose/tratamento farmacológico , Aterosclerose/prevenção & controle , Berberina/farmacologia , Berberina/uso terapêutico , Lipoproteínas HDL , Lipoproteínas LDL , Camundongos , Camundongos Knockout para ApoE , Triglicerídeos
9.
Acta Pharmacol Sin ; 43(9): 2351-2361, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35149852

RESUMO

Nuclear receptor corepressor 1 (NCoR1) is a corepressor of the epigenetic regulation of gene transcription that has important functions in metabolism and inflammation, but little is known about its role in alcohol-associated liver disease (ALD). In this study, we developed mice with hepatocyte-specific NCoR1 knockout (NCoR1Hep-/-) using the albumin-Cre/LoxP system and investigated the role of NCoR1 in the pathogenesis of ALD and the underlying mechanisms. The traditional alcohol feeding model and NIAAA model of ALD were both established in wild-type and NCoR1Hep-/- mice. We showed that after ALD was established, NCoR1Hep-/- mice had worse liver injury but less steatosis than wild-type mice. We demonstrated that hepatocyte-specific loss of NCoR1 attenuated liver steatosis by promoting fatty acid oxidation by upregulating BMAL1 (a circadian clock component that has been reported to promote peroxisome proliferator activated receptor alpha (PPARα)-mediated fatty ß-oxidation by upregulating de novo lipid synthesis). On the other hand, hepatocyte-specific loss of NCoR1 exacerbated alcohol-induced liver inflammation and oxidative stress by recruiting monocyte-derived macrophages via C-C motif chemokine ligand 2 (CCL2). In the mouse hepatocyte line AML12, NCoR1 knockdown significantly increased ethanol-induced CCL2 release. These results suggest that hepatocyte NCoR1 plays distinct roles in controlling liver inflammation and steatosis, which provides new insights into the development of treatments for steatohepatitis induced by chronic alcohol consumption.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas , Fígado Gorduroso , Hepatopatias Alcoólicas , Animais , Quimiocinas/metabolismo , Modelos Animais de Doenças , Epigênese Genética , Etanol/toxicidade , Hepatócitos/metabolismo , Inflamação/metabolismo , Ligantes , Fígado/metabolismo , Hepatopatias Alcoólicas/patologia , Macrófagos/metabolismo , Camundongos , Camundongos Knockout , Correpressor 1 de Receptor Nuclear/genética , Correpressor 1 de Receptor Nuclear/metabolismo
10.
Molecules ; 27(3)2022 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-35163972

RESUMO

With the widespread clinical use of drug combinations, the incidence of drug-drug interactions (DDI) has significantly increased, accompanied by a variety of adverse reactions. Drug transporters play an important role in the development of DDI by affecting the elimination process of drugs in vivo, especially in the pathological state. Tubulointerstitial fibrosis (TIF) is an inevitable pathway in the progression of chronic kidney disease (CKD) to end-stage renal disease. Here, the dynamic expression changes of eleven drug transporters in TIF kidney have been systematically investigated. Among them, the mRNA expressions of Oat1, Oat2, Oct1, Oct2, Oatp4C1 and Mate1 were down-regulated, while Oat3, Mrp2, Mrp4, Mdr1-α, Bcrp were up-regulated. Pearson correlation analysis was used to analyze the correlation between transporters and Creatinine (Cr), OCT2 and MATE1 showed a strong negative correlation with Cr. In contrast, Mdr1-α exhibited a strong positive correlation with Cr. In addition, the pharmacokinetics of cimetidine, ganciclovir, and digoxin, which were the classical substrates for OCT2, MATE1 and P-glycoprotein (P-gp), respectively, have been studied. These results reveal that changes in serum creatinine can indicate changes in drug transporters in the kidney, and thus affect the pharmacokinetics of its substrates, providing useful information for clinical use.


Assuntos
Proteínas de Transporte de Ânions/farmacocinética , Nefropatias/tratamento farmacológico , Transportadores de Ânions Orgânicos/farmacocinética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Animais , Proteínas de Transporte de Ânions/farmacologia , Transporte Biológico , China , Creatinina/metabolismo , Interações Medicamentosas , Fibrose , Rim/metabolismo , Rim/patologia , Nefropatias/metabolismo , Falência Renal Crônica/patologia , Masculino , Transportadores de Ânions Orgânicos/farmacologia , Proteínas de Transporte de Cátions Orgânicos/genética , Preparações Farmacêuticas/metabolismo , Ratos , Ratos Sprague-Dawley
11.
Molecules ; 26(20)2021 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-34684685

RESUMO

Chemical compositions, antioxidants, and anti-aging activities of Cortex Moutan (CM), from different collection periods and different producing areas, were measured and compared in order to obtain excellent CM extracts. The bioactivities of CM extracts were examined by an in vitro antioxidant method and a UVB irradiated human dermal fibroblast (HDF) model. Phytochemical properties were obtained from ultra-fast liquid chromatography quadrupole time-of-flight mass spectrometry (UFLC-Q-TOF-MS) prior to the multivariate statistical analysis. As for the results, the extracts of Heze CM (HZCM) and Luoyang CM (LYCM) collected in June had better in vitro antioxidant activities, significantly increased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and reduced the content of malondialdehyde (MDA), compared to other CM extracts. HZCM and LYCM extracts could upregulate the relative expression of SOD and GSH-Px mRNA. The extract of HZCM collected in June could significantly repress the production of matrix metalloproteinase 1 (MMP-1) and improve the production of procollagen type I (PCOL)-I in UVB irradiated HDF. In total, 50 compounds, including 17 monoterpenoids, 19 flavonoids, 13 phenols, and 1 amino acid were identified or tentatively identified in the CM extracts. Gallic acid, p-hydroxybenzoic acid, oxypaeoniflorin, paeoniflorin, 1,2,3,4,6-O-pentagalloyl glucose, and paeonol were predominant compounds in the CM extracts. Taken together, CM collected from April to September had better antioxidant and anti-aging effects for external usage.


Assuntos
Antioxidantes/farmacologia , Paeonia/química , Compostos Fitoquímicos/farmacologia , Linhagem Celular , Cromatografia Líquida de Alta Pressão/métodos , Glutationa Peroxidase/metabolismo , Humanos , Malondialdeído/metabolismo , Espectrometria de Massas/métodos , Paeonia/metabolismo , Fenóis/química , Compostos Fitoquímicos/química , Casca de Planta/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Estações do Ano , Superóxido Dismutase/metabolismo
12.
Toxicol Appl Pharmacol ; 359: 91-101, 2018 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-30248416

RESUMO

Aggravating effect of probenecid (a traditional anti-gout agent) on emodin-induced hepatotoxicity was evaluated in this study. 33.3% rats died in combination group, while no death was observed in rats treated with emodin alone or probenecid alone, indicating that emodin-induced (150 mg/kg) hepatotoxicity was exacerbated by probenecid (100 mg/kg). In toxicokinetics-toxicodynamics (TK-TD) study, aspartate aminotransferase (AST) and systemic exposure (area under the serum concentration-time curve, AUC) of emodin and its glucuronide were significantly increased in rats after co-administrated with emodin and probenecid for 28 consecutive days. Results showed that the increased AUC (increased by 85.9%) of emodin was mainly caused by the decreased enzyme activity of UDP-glucuronosyltransferases (UGTs, decreased by 11.8%-58.1%). In addition, AUC of emodin glucuronide was increased 5-fold, which was attributed to the decrease of multidrug-resistant-protein 2 (MRP2) protein levels (decreased by 54.4%). Similarly, in vitro experiments proved that probenecid reduced the cell viability of emodin-treated HepG2 cells through inhibiting UGT1A9, UGT2B7 and MRP2. Our findings demonstrated that emodin-induced hepatoxicity was exacerbated by probenecid through inhibition of UGTs and MRP2 in vivo and in vitro, indicating that gout patients should avoid taking emodin-containing preparations in combination with probenecid for a long time.


Assuntos
Transportadores de Cassetes de Ligação de ATP/antagonistas & inibidores , Catárticos/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/patologia , Emodina/toxicidade , Glucuronosiltransferase/antagonistas & inibidores , Probenecid/toxicidade , Fármacos Renais/toxicidade , Animais , Catárticos/farmacocinética , Sobrevivência Celular/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/enzimologia , Sinergismo Farmacológico , Emodina/farmacocinética , Células Hep G2 , Humanos , Cinética , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/enzimologia , Probenecid/farmacocinética , Ratos , Ratos Sprague-Dawley , Fármacos Renais/farmacocinética
13.
Int J Mol Sci ; 19(7)2018 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-30002289

RESUMO

Hedyotis diffusa is a folk herb that is used for treating inflammation-related diseases in Asia. Previous studies have found that iridoids in H. diffusa play an important role in its anti-inflammatory activity. This study aimed to investigate the anti-inflammatory effect and potential mechanism of five iridoids (asperuloside (ASP), asperulosidic acid (ASPA), desacetyl asperulosidic acid (DAA), scandoside methyl ester (SME), and E-6-O-p-coumaroyl scandoside methyl ester (CSME)) that are presented in H. diffusa using lipopolysaccharide (LPS)-induced RAW 264.7 cells. ASP and ASPA significantly decreased the production of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in parallel with the inhibition of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α, and IL-6 mRNA expression in LPS-induced RAW 264.7 cells. ASP treatment suppressed the phosphorylation of the inhibitors of nuclear factor-kappaB alpha (IκB-α), p38, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK). The inhibitory effect of ASPA was similar to that of ASP, except for p38 phosphorylation. In summary, the anti-inflammatory effects of ASP and ASPA are related to the inhibition of inflammatory cytokines and mediators via suppression of the NF-κB and mitogen-activated protein kinase (MAPK) signaling pathways, which provides scientific evidence for the potential application of H. diffusa.


Assuntos
Anti-Inflamatórios/farmacologia , Glucosídeos/farmacologia , Glicosídeos/farmacologia , Lipopolissacarídeos/toxicidade , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , NF-kappa B/metabolismo , Piranos/farmacologia , Animais , Monoterpenos Ciclopentânicos , Macrófagos/patologia , Camundongos , Células RAW 264.7
14.
Int J Mol Sci ; 19(2)2018 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-29401674

RESUMO

The iridoids of Hedyotis diffusa Willd play an important role in the anti-inflammatory process, but the specific iridoid with anti-inflammatory effect and its mechanism has not be thoroughly studied. An iridoid compound named scandoside (SCA) was isolated from H. diffusa and its anti-inflammatory effect was investigated in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. Its anti-inflammatory mechanism was confirmed by in intro experiments and molecular docking analyses. As results, SCA significantly decreased the productions of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and inhibited the levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α and IL-6 messenger RNA (mRNA) expression in LPS-induced RAW 264.7 macrophages. SCA treatment suppressed the phosphorylation of inhibitor of nuclear transcription factor kappa-B alpaha (IκB-α), p38, extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK). The docking data suggested that SCA had great binding abilities to COX-2, iNOS and IκB. Taken together, the results indicated that the anti-inflammatory effect of SCA is due to inhibition of pro-inflammatory cytokines and mediators via suppressing the nuclear transcription factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, which provided useful information for its application and development.


Assuntos
Anti-Inflamatórios/farmacologia , Hedyotis/química , Iridoides/farmacologia , Lipopolissacarídeos/antagonistas & inibidores , NF-kappa B/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Sobrevivência Celular/efeitos dos fármacos , Ciclo-Oxigenase 2/química , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/antagonistas & inibidores , Dinoprostona/biossíntese , Quinase I-kappa B/antagonistas & inibidores , Quinase I-kappa B/química , Quinase I-kappa B/genética , Quinase I-kappa B/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Iridoides/química , Iridoides/isolamento & purificação , Proteínas Quinases JNK Ativadas por Mitógeno/genética , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Lipopolissacarídeos/farmacologia , Camundongos , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Simulação de Acoplamento Molecular , NF-kappa B/genética , NF-kappa B/metabolismo , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II/química , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Extratos Vegetais/química , Células RAW 264.7 , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
15.
Biomed Chromatogr ; 31(12)2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28557019

RESUMO

Humantenmine (HMT), the most toxic compound isolated from Gelsemium elegans Benth, is a well-known active herbal compound. A rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated to estimate the absolute oral bioavailability of HMT in rats. Quantification was performed by multiple reaction monitoring using electrospray ionization operated in positive ion mode with transitions of m/z 327.14 → m/z 296.19 for HMT and m/z 323.20 → m/z 236.23 for gelsemine (internal standard, IS). The linear range of the calibration curve was 1-256 nmol/L, with a lower limit of quantification at 1 nmol/L. The accuracy of HMT ranged from 89.39 to 107.5%, and the precision was within 12.24% (RSD). Excellent recovery and negligible matrix effect were observed. HMT remained stable during storage, preparation and analytical procedures. The pharmacokinetics of HMT in rats showed that HMT reached the concentration peak at 12.50 ± 2.74 min with a peak concentration of 28.49 ± 6.65 nmol/L, and the corresponding area under the concentration-time curve (AUC0-t ) was 1142.42 ± 202.92 nmol/L min after 200 µg/kg HMT was orally administered to rats. The AUC0-t of HMT given at 20 µg/kg by tail vein administration was 1518.46 ± 192.24 nmol/L min. The calculated absolute bioavailability of HMT was 7.66%.


Assuntos
Alcaloides/sangue , Alcaloides/farmacocinética , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas em Tandem/métodos , Alcaloides/química , Animais , Disponibilidade Biológica , Estabilidade de Medicamentos , Modelos Lineares , Masculino , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
16.
Molecules ; 22(9)2017 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-28869577

RESUMO

Forsythiae Fructus, as a traditional Chinese medicine, has been widely used both as a single herb and in compound prescriptions in Asia, mainly due to its heat-clearing and detoxifying effects. Modern pharmacology has proved Forsythiae Fructus possesses various therapeutic effects, both in vitro and in vivo, such as anti-inflammatory, antibacterial and antiviral activities. Up to now, three hundred and twenty-one compounds have been identified and sensitive analytical methods have been established for its quality control. Recently, the pharmacokinetics of Forsythiae Fructus and its bioactive compounds have been reported, providing valuable information for its clinical application. Therefore, this systematic review focused on the newest scientific reports on Forsythiae Fructus and extensively summarizes its phytochemistry, pharmacology, pharmacokinetics and standardization procedures, especially the difference between the two applied types-unripe Forsythiae Fructus and ripe Forsythiae Fructus-in the hope of providing a helpful reference and guide for its clinical applications and further studies.


Assuntos
Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Forsythia/química , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Anti-Inflamatórios/farmacocinética , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacocinética , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/química , Antioxidantes/farmacocinética , Antioxidantes/farmacologia , Antivirais/química , Antivirais/farmacocinética , Antivirais/farmacologia , Descoberta de Drogas , Medicamentos de Ervas Chinesas/farmacocinética , Humanos , Compostos Fitoquímicos/farmacocinética
17.
Molecules ; 21(6)2016 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-27248992

RESUMO

Hedyotis diffusa Willd (H. diffusa) is a well-known Chinese medicine with a variety of activities, especially its anti-cancer effect in the clinic. Up to now, 171 compounds have been reported from H. diffusa, including 32 iridoids, 26 flavonoids, 24 anthraquinones, 26 phenolics and their derivatives, 50 volatile oils and 13 miscellaneous compounds. In vitro and in vivo studies show these phytochemicals and plant extracts to exhibit a range of pharmacological activities of anti-cancer, antioxidant, anti-inflammatory, anti-fibroblast, immunomodulatory and neuroprotective effects. Although a series of methods have been established for the quality control of H. diffusa, a feasible and reliable approach is still needed in consideration of its botanical origin, collecting time and bioactive effects. Meanwhile, more pharmacokinetics researches are needed to illustrate the characteristics of H. diffusa in vivo. The present review aims to provide up-to-date and comprehensive information on the phytochemistry, pharmacology, quality control and pharmacokinetic characteristics of H. diffusa for its clinical use and further development.


Assuntos
Extratos Vegetais/química , Extratos Vegetais/farmacologia , Rubiaceae/química , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/normas , Humanos , Fatores Imunológicos/química , Fatores Imunológicos/farmacologia , Metabolômica/métodos , Processos Fotoquímicos , Fotoquímica , Compostos Fitoquímicos , Extratos Vegetais/normas , Controle de Qualidade
18.
Molecules ; 21(9)2016 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-27618004

RESUMO

Both Rosa roxburghii and R. sterilis, belonging to the Rosaceae, are endemic species in Guizhou Province, China. The fruits of these two species are mixed-used as functional food in the region. Aiming to elucidate the phytochemical characteristics of R. roxburghii and R. sterilis fruits, the essential oils and constituents in a methanol extract have been analyzed and compared by GC-MS and UFLC/Q-TOF-MS, respectively. As a result, a total of 135 volatile compounds were identified by GC-MS and 91 components were different between R. roxburghii and R. sterilis fruits; a total of 59 compounds in methanol extracts were identified by UFLC/Q-TOF-MS, including 13 organic acids, 12 flavonoids, 11 triterpenes, nine amino acids, five phenylpropanoid derivatives, four condensed tannins, two stilbenes, two benzaldehyde derivatives and one benzoic acid derivative; and nine characteristic compounds were found between R. roxburghii and R. sterilis fruits. This systematic study plays an important role for R. roxburghii and R. sterilis fruits in the product development.


Assuntos
Análise de Alimentos , Frutas/química , Extratos Vegetais/análise , Rosa/química
19.
Int J Mol Sci ; 16(11): 27252-69, 2015 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-26580602

RESUMO

Protective effect of Hedyotis diffusa (H. diffusa) Willd against lipopolysaccharide (LPS)-induced renal inflammation was evaluated by the productions of cytokines and chemokine, and the bioactive constituents of H. diffusa were detected by the ultra-fast liquid chromatography-diode array detector-quadrupole-time of flight mass spectrometry (UFLC-DAD-Q-TOF-MS/MS) method. As the results showed, water extract of H. diffusa (equal to 5.0 g/kg body weight) obviously protected renal tissues, significantly suppressed the productions of tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-6, and monocyte chemoattractant protein (MCP)-1, as well as significantly promoted the production of IL-10 in serum and renal tissues. According the chemical profiles of H. diffusa, flavonoids, iridoid glycosides and anthraquinones were greatly detected in serum from H. diffusa extract treatment mice. Two main chemotypes, including eight flavonoids and four iridoid glycosides were found in renal tissues from H. diffusa extract treatment mice. The results demonstrated that water extract of H. diffusa had protective effect on renal inflammation, which possibly resulted from the bioactive constituents consisting of flavonoids, iridoids and anthraquinones.


Assuntos
Hedyotis/química , Nefrite/metabolismo , Nefrite/patologia , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Animais , Quimiocinas/biossíntese , Cromatografia Líquida de Alta Pressão , Citocinas/biossíntese , Lipopolissacarídeos/efeitos adversos , Macrófagos/metabolismo , Macrófagos/patologia , Camundongos , Nefrite/induzido quimicamente , Nefrite/tratamento farmacológico , Extratos Vegetais/química , Substâncias Protetoras/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Espectrometria de Massas em Tandem
20.
Int J Mol Sci ; 16(3): 5047-71, 2015 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-25751722

RESUMO

Radix Astragali (RA) is one of the commonly-used traditional Chinese medicines (TCMs) with an immunomodulatory effect confirmed in the clinic. In order to better understand the material basis for the therapeutic effects, this study was to investigate the absorbed components and their pharmacokinetic profile after oral administration of RA on cyclophosphamide-induced immunosuppression in Balb/c mice. As a result, 51 compounds in RA extract and 31 prototype compounds with nine metabolites were detected in mice plasma by the ultra-fast liquid chromatography (UFLC)-DAD-Q-TOF-MS/MS method. The pharmacokinetic parameters of five main constituents, including calycosin-7-O-glucoside, ononin, calycosin, formononetin and astragaloside IV, were obtained using HPLC-MS/MS. These results offered useful information for research on the pharmacological mechanism of RA and for its further development.


Assuntos
Ciclofosfamida/farmacologia , Medicamentos de Ervas Chinesas/química , Tolerância Imunológica/efeitos dos fármacos , Imunossupressores/farmacologia , Administração Oral , Animais , Astragalus propinquus/química , Astragalus propinquus/metabolismo , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/análise , Medicamentos de Ervas Chinesas/farmacocinética , Masculino , Medicina Tradicional Chinesa , Camundongos , Camundongos Endogâmicos BALB C , Raízes de Plantas/química , Raízes de Plantas/metabolismo , Espectrometria de Massas por Ionização por Electrospray
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