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1.
Int J Mol Sci ; 22(15)2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34360801

RESUMO

Senna and rhubarb are often used as routine laxatives, but there are differences in mechanism of action and potential side effects. Here, we studied metabolites of senna anthraquinones (SAQ), rhubarb anthraquinones (RAQ) and their chemical marker, sennoside A (SA), in a rat diarrhea model. In in vitro biotransformation experiments, SAQ, RAQ and SA were incubated with rat fecal flora solution and the metabolites produced were analyzed using HPLC. In in vivo studies, the same compounds were investigated for purgation induction, with measurement of histopathology and Aqps gene expression in six organs. The results indicated that SAQ and RAQ had similar principal constituents but could be degraded into different metabolites. A similar profile of Aqps down-regulation for all compounds was seen in the colon, suggesting a similar mechanism of action for purgation. However, in the kidneys and livers of the diarrhea-rats, down-regulation of Aqps was found in the RAQ-rats whereas up-regulation of Aqps was seen in the SAQ-rats. Furthermore, the RAQ-rats showed lower Aqp2 protein expression in the kidneys, whilst the SA-rats and SAQ-rats had higher Aqp2 protein expression in the kidneys. This may have implications for side effects of SAQ or RAQ in patients with chronic kidney or liver diseases.


Assuntos
Aquaporina 2/biossíntese , Regulação da Expressão Gênica/efeitos dos fármacos , Rim/metabolismo , Fígado/metabolismo , Rheum/química , Senna/química , Senosídeos/farmacologia , Animais , Masculino , Especificidade de Órgãos/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Senosídeos/química
2.
Int J Biol Macromol ; 178: 424-433, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33662415

RESUMO

Amyloid proteins were recognized as the crucial cause of many senile diseases. In this study, the inhibitory effects of Sennoside A (SA) and Sennoside C (SC) on amyloid fibrillation were evaluated by the combination of biophysical approaches and molecular docking tool using human lysozyme (HL) as amyloid-forming model. The results of thioflavin-T (ThT), 8-anilino-1-naphthalenesulfonic acid (ANS) and congo red (CR) assays indicated that both SA and SC could inhibit the amyloid fibrillation of HL in a dose-dependent manner. The IC50 value of SA and SC on HL fibrillation was 200.09 µM and 186.20 µM, respectively. These findings were further verified by transmission electron microscopy (TEM) and atomic force microscopy (AFM), which showed that the addition of SA or SC could sharply reduce the amyloid fibrillation of HL. Additionally, the interactions of HL with SA and SC were investigated by steady-state fluorescence spectra and molecular docking studies. The results suggested that both SA and SC could bind to the binding pocket of HL and form a stable complex mainly via hydrogen bonds, van-der-Waals forces and hydrophobic interactions. In conclusion, our experiments revealed that both SA and SC can significantly inhibit amyloid fibrillation of HL.


Assuntos
Amiloide/química , Muramidase/química , Agregados Proteicos , Extrato de Senna/química , Senosídeos/química , Humanos
3.
Artigo em Inglês | MEDLINE | ID: mdl-31874099

RESUMO

Background This study evaluates the antioxidant activity and enzyme inhibitory properties of the n-butanol fraction of Senna podocarpa leaves on α-amylase, α-glucosidase, acetylcholinesterase (AChE), butyrylcholinesterase (BChE), tyrosinase, arginase, phosphodiesterase 5 (PDE-5), and angiotensin converting enzyme (ACE). Methods The total phenol and flavonoids, iron (Fe) chelation, and 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) free radical scavenging were used to determine the antioxidant activity, and the inhibitory activities of α-glucosidase, α-amylase, AChE, BChE, tyrosinase, arginase, PDE-5 and ACE were also assessed. Results The n-butanol fraction of S. podocarpa shows high total phenol and total flavonoid contents. The n-butanol fraction of S. podocarpa leaves also chelates Fe2+ and ABTS radicals. The n-butanol fraction of S. podocarpa leaves also inhibited α-glucosidase, α-amylase, AChE, BChE, tyrosinase, arginase, PDE-5, and ACE at the concentration tested. Chromatographic analysis displayed the presence of ß-elemene, phytol and caryophyllene oxide chrysophanol, 3-oxo-methyl ester, α-humulene, ß-caryophyllene, rhein, emodin, and α-copaene. Conclusions Hence, the n-butanol fraction of S. podocarpa leaves demonstrates encouraging feat in controlling and/or managing cognitive dysfunction such as Alzheimer's disease and also hypertension, diabetes, erectile dysfunction, endothelial dysfunction, and hyperpigmentation.


Assuntos
1-Butanol/química , Antioxidantes/química , Inibidores Enzimáticos/química , Fabaceae/química , Folhas de Planta/química , Animais , Flavonoides/química , Masculino , Fenóis/química , Extratos Vegetais/química , Ratos , Ratos Wistar , Senosídeos/química
4.
Metabolomics ; 15(5): 80, 2019 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-31087208

RESUMO

INTRODUCTION: The demand to develop efficient and reliable analytical methods for the quality control of nutraceuticals is on the rise, together with an increase in the legal requirements for safe and consistent levels of its active principles. OBJECTIVE: To establish a reliable model for the quality control of widely used Senna preparations used as laxatives and assess its phyto-equivalency. METHODS: A comparative metabolomics approach via NMR and MS analyses was employed for the comprehensive measurement of metabolites and analyzed using chemometrics. RESULTS: Under optimized conditions, 30 metabolites were simultaneously identified and quantified including anthraquinones, bianthrones, acetophenones, flavonoid conjugates, naphthalenes, phenolics, and fatty acids. Principal component analysis (PCA) was used to define relative metabolite differences among Senna preparations. Furthermore, quantitative 1H NMR (qHNMR) was employed to assess absolute metabolites levels in preparations. Results revealed that 6-hydroxy musizin or tinnevellin were correlated with active metabolites levels, suggesting the use of either of these naphthalene glycosides as markers for official Senna drugs authentication. CONCLUSION: This study provides the first comparative metabolomics approach utilizing NMR and UPLC-MS to reveal for secondary metabolite compositional differences in Senna preparations that could readily be applied as a reliable quality control model for its analysis.


Assuntos
Metabolômica , Senosídeos/metabolismo , Acetofenonas/metabolismo , Antracenos/metabolismo , Antraquinonas/metabolismo , Flavonoides/metabolismo , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Estrutura Molecular , Naftalenos/metabolismo , Fenóis/metabolismo , Análise de Componente Principal , Controle de Qualidade , Senosídeos/química
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