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Traditional Chinese medicine (TCM) has a long history in the treatment of chronic hepatitis B (CHB) based on the syndrome identification. Previous studies reported CHB patients with damp-heat (DH) syndrome accompanied with a severe liver function damage, but lacked the medication analysis. In this study, we analyzed 999 CHB patients with unidentified individual-level data from database to explore clinical features of two common syndromes of CHB patients based on the real world. Compared with the spleen deficiency (SD) syndrome, the CHB patients with DH syndrome had a significantly higher level of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (P < 0.05) but took more immunomodulators and hepatoprotective drugs (P < 0.1). Similarly, in the follow-up of 207 patients after 3 months, the improvement trend of ALT and AST of patients with sustained SD syndrome was significantly better than those whose TCM syndrome changed from SD to DH (P < 0.05). The logistic model indicated DH syndrome was a significant negative factor for reducing ALT level in CHB patients (OR = 4.854, P=0.032). This study suggests that CHB patients with DH syndrome have potentially more serious and sustained liver damage than the SD syndrome, which provides a reference for the personalized management of CHB patients from the perspective of TCM syndromes.
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AIM: To elucidate tongue coating microbiota and metabolic differences in chronic hepatitis B (CHB) patients with yellow or white tongue coatings. METHODS: Tongue coating samples were collected from 53 CHB patients (28 CHB yellow tongue coating patients and 25 CHB white tongue coating patients) and 22 healthy controls. Microbial DNA was extracted from the tongue samples, and the bacterial 16S ribosomal RNA gene V3 region was amplified from all samples and sequenced with the Ion Torrent PGM™ sequencing platform according to the standard protocols. The metabolites in the tongue coatings were evaluated using a liquid chromatography-mass spectrometry (LC-MS) platform. Statistical analyses were then performed. RESULTS: The relative compositions of the tongue coating microbiotas and metabolites in the CHB patients were significantly different from those of the healthy controls, but the tongue coating microbiota abundances and diversity levels were not significantly different. Compared with the CHB white tongue coating patients, the CHB yellow tongue coating patients had higher hepatitis B viral DNA (HBV-DNA) titers (median 21210 vs 500, respectively, P = 0.03) and a significantly lower level of Bacteroidetes (20.14% vs 27.93%, respectively, P = 0.013) and higher level of Proteobacteria (25.99% vs 18.17%, respectively, P = 0.045) in the microbial compositions at the phylum level. The inferred metagenomic pathways enriched in the CHB yellow tongue coating patients were mainly those involved in amino acid metabolism, which was consistent with the metabolic disorder. The abundances of bacteria from Bacteroidales at the order level were higher in the CHB white tongue coating patients (19.2% vs 27.22%, respectively, P = 0.011), whereas Neisseriales were enriched in the yellow tongue coating patients (21.85% vs 13.83%, respectively, P = 0.029). At the family level, the abundance of Neisseriaceae in the yellow tongue patients was positively correlated with the HBV-DNA level but negatively correlated with the S-adenosyl-L-methionine level. CONCLUSION: This research illustrates specific clinical features and bacterial structures in CHB patients with different tongue coatings, which facilitates understanding of the traditional tongue diagnosis.
Assuntos
Bactérias/isolamento & purificação , Microbioma Gastrointestinal/fisiologia , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/microbiologia , Língua/microbiologia , Adulto , Bactérias/genética , Bactérias/metabolismo , Estudos de Casos e Controles , DNA Viral/isolamento & purificação , Feminino , Voluntários Saudáveis , Vírus da Hepatite B/genética , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/metabolismo , Humanos , Masculino , Medicina Tradicional Chinesa/métodos , Metagenômica , Pessoa de Meia-Idade , RNA Ribossômico 16S/genéticaRESUMO
A novel series of donepezil-trolox hybrids were designed, synthesized, and evaluated as multifunctional ligands against Alzheimer's disease (AD). Biological assays showed that these derivatives possessed moderate to good inhibitory activities against acetylcholinesterase (AChE) and monoamine oxidase B (MAO-B) as well as remarkable antioxidant effects. The optimal compound 6d exhibited balanced functions with good inhibition against hAChE (IC50 = 0.54 µM) and hMAO-B (IC50 = 4.3 µM), significant antioxidant activity (41.33 µM IC50 by DPPH method, 1.72 and 1.79 trolox equivalent by ABTS and ORAC methods), excellent copper chelation, and Aß1-42 aggregation inhibition effect. Furthermore, cellular tests indicated that 6d has very low toxicity and is capable of combating oxidative toxin (H2O2, rotenone, and oligomycin-A) induced neurotoxicity. Most importantly, oral administration of 6d demonstrated notable improvements on cognition and spatial memory against scopolamine-induced acute memory deficit as well as d-galactose (d-gal) and AlCl3 induced chronic oxidative stress in a mouse model without acute toxicity and hepatotoxicity. In summary, both in vitro and in vivo results suggested that 6d is a valuable candidate for the development of a safe and effective anti-Alzheimer's drug.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Antioxidantes/uso terapêutico , Fármacos do Sistema Nervoso Central/uso terapêutico , Inibidores da Colinesterase/uso terapêutico , Cromanos/uso terapêutico , Indanos/uso terapêutico , Inibidores da Monoaminoxidase/uso terapêutico , Piperidinas/uso terapêutico , Peptídeos beta-Amiloides/efeitos dos fármacos , Animais , Antioxidantes/farmacologia , Antioxidantes/toxicidade , Barreira Hematoencefálica , Linhagem Celular , Fármacos do Sistema Nervoso Central/farmacologia , Fármacos do Sistema Nervoso Central/toxicidade , Quelantes/farmacologia , Quelantes/uso terapêutico , Quelantes/toxicidade , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/toxicidade , Cromanos/farmacologia , Cromanos/toxicidade , Cobre , Donepezila , Desenho de Fármacos , Avaliação Pré-Clínica de Medicamentos , Humanos , Indanos/farmacologia , Indanos/toxicidade , Masculino , Camundongos Endogâmicos ICR , Microglia/efeitos dos fármacos , Simulação de Acoplamento Molecular , Inibidores da Monoaminoxidase/farmacologia , Inibidores da Monoaminoxidase/toxicidade , Neurotoxinas/toxicidade , Oxidantes/toxicidade , Células PC12 , Fragmentos de Peptídeos/efeitos dos fármacos , Piperidinas/farmacologia , Piperidinas/toxicidade , Agregação Patológica de Proteínas/tratamento farmacológico , Ratos , Relação Estrutura-AtividadeRESUMO
BACKGROUND: To elucidate whether rice protein can possess a vital function in improving lipids level and adiposity, the effects of rice proteins extracted by alkaline (RP-A) and α-amylase (RP-E) on triglyceride metabolism were investigated in 7-week-old male Wistar rats fed cholesterol-enriched diets for 2 weeks, as compared with casein (CAS). RESULTS: Compared with CAS, plasma concentrations of glucose and lipids were significantly reduced by RP-feeding (P < 0.05), as well as hepatic accumulation of lipids (P < 0.05). RP-A and RP-E significantly depressed the hepatic activities of fatty acid synthase (FAS), glucose 6-phosphate dehydrogenase (G6PD) and malate dehydrogenase (MDH) (P < 0.05), whereas the activities of lipoprotein lipase (PL) and hepatic lipase (HL) were significantly stimulated (P < 0.05), as compared to CAS. Neither lipids level nor activities of enzymes were different between RP-A and RP-E (P > 0.05). There was a significant positive correlation between protein digestibility and deposit fat (r = 0.8567, P < 0.05), as well as the plasma TG concentration (r = 0.8627, P < 0.05). CONCLUSIONS: The present study demonstrates that rice protein can modify triglyceride metabolism, leading to an improvement of body weight and adiposity. Results suggest that the triglyceride-lowering action as well as the potential of anti-adiposity induced by rice protein is attributed to upregulation of lipolysis and downregulation of lipogenesis, and the lower digestibility of rice protein may be the main modulator responsible for the lipid-lowering action.
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Adiposidade/efeitos dos fármacos , Fármacos Antiobesidade/farmacologia , Lipídeos/sangue , Lipotrópicos/farmacologia , Oryza/química , Extratos Vegetais/farmacologia , Proteínas de Plantas/farmacologia , Triglicerídeos/metabolismo , Redução de Peso/efeitos dos fármacos , Alanina Transaminase/sangue , Aminoácidos/sangue , Animais , Fármacos Antiobesidade/isolamento & purificação , Aspartato Aminotransferases/sangue , Dieta Hiperlipídica , Fezes/química , Lipogênese/efeitos dos fármacos , Lipólise/efeitos dos fármacos , Lipotrópicos/isolamento & purificação , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/metabolismo , Masculino , Extratos Vegetais/isolamento & purificação , Proteínas de Plantas/isolamento & purificação , Ratos , Ratos WistarRESUMO
INTRODUCTION: Esophageal cancer consists of two distinct types, esophageal adenocarcinoma (EAC) and squamous cell carcinoma, both of which differ significantly in their etiology. Freeze-dried black raspberry (BRB) has been consistent in its ability to modulate the biomarkers and reduce the incidence of carcinogen-induced squamous cell carcinoma in rats. In our previous studies in the esophagoduodenal anastomosis (EDA) model, we have shown that the early modulation of manganese superoxide dismutase (MnSOD) significantly correlates with the development of reflux-induced EAC in rats. In this study we looked at the short-term effects of a BRB-supplemented diet on the modulation of antioxidant enzymes in reflux-induced esophagitis. METHODS: Male SD rats (8 wk old; n = 3-5) were randomized into three groups--sham-operated, fed control AIN-93M diet (SH-CD), EDA operated and fed either control diet (EDA-CD) or 2.5% (w/w) BRB diet (EDA-BRB). The effect of both reflux and dietary supplementation was analyzed 2 and 4 wk after EDA surgery. RESULTS: Animals in the EDA groups had significantly lower weight gain and diet intake compared to SH-CD (P < 0.05). The sham-operated animals received an average esophagitis score of 0.1 ± 0.1; this increased significantly in EDA-CD animals to 1.8 ± 0.14 (P < 0.001 versus SH-CD) and in EDA-BRB group to 1.7 ± 0.06 (P < 0.001 versus SH-CD), with BE changes also present. However, dietary supplementation of BRB did not alter or ameliorate the grade of esophagitis or the induction of BE. BRB diet caused a 43% increase in MnSOD levels compared to EDA-CD (0.73 ± 0.16; P = 0.09); however, this effect was not statistically significant and at 4 wk, EDA-CD (0.58 ± 0.12) showed an increase in MnSOD expression compared to SH-CD (0.34 ± 0.01). CONCLUSIONS: In conclusion, our data suggest that dietary BRB does not increase the levels of cellular antioxidant enzymes or reduce the levels of lipid peroxidation compared to a control diet, in a short-term study of gastroesophageal reflux induction in the EDA animal model. However, it remains to be tested whether this is indicative of its ineffectiveness to inhibit reflux-induced EAC incidence over the long term.