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Herbal formula, Scutellariae radix and Rhei rhizoma attenuate dimethylnitrosamine-induced liver fibrosis in a rat model.

ABSTRACT: The bioactive components extracted from Scutellariae radix and Rhei rhizoma (SR) have been commonly used to treat liver diseases. The aim of this study was to verify the underlying mechanisms and antifibrotic effects of ethanol extract from the herbal combinatorial formula (SRE) in a dimethylnitrosamine (DMN)-administered rat model, with functional proteome tools. Our results indicated that the hepatic collagen content and alpha-smooth muscle actin expression were obviously alleviated by treatment with SRE. Comprehensive proteomics revealed global protein changes, and the network analysis implied that SRE application would attenuate oxidative stress and cytoskeleton dysregulation caused by DMN exposure. Next, marked downregulation of antioxidant enzymes mediated by DMN treatment was restored in the presence of SRE, while SRE treatment contributed to decreased MDA content. Moreover, protein carbonylation and DNA adduction induced by oxidative stress finally leading to liver injury were also reduced under SRE administration. These findings demonstrate that SRE could effectively prevent hepatic fibrosis mainly through regulating the redox status, and subsequently modulating the modification of intracellular molecules. Our experiments might help in developing novel therapeutic strategies against oxidation-caused liver diseases.

SUBMITTER: Pan TL

PROVIDER: S-EPMC4488958 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Herbal formula, Scutellariae radix and Rhei rhizoma attenuate dimethylnitrosamine-induced liver fibrosis in a rat model.

Pan Tai-Long TL Wang Pei-Wen PW Huang Chun-Hsun CH Leu Yann-Lii YL Wu Tung-Ho TH Wu Yun-Ru YR You Jyh-Sheng JS

Scientific reports 20150702

The bioactive components extracted from Scutellariae radix and Rhei rhizoma (SR) have been commonly used to treat liver diseases. The aim of this study was to verify the underlying mechanisms and antifibrotic effects of ethanol extract from the herbal combinatorial formula (SRE) in a dimethylnitrosamine (DMN)-administered rat model, with functional proteome tools. Our results indicated that the hepatic collagen content and alpha-smooth muscle actin expression were obviously alleviated by treatme ...[more]

PMID: 26133262

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Project description:Aim Scutellariae Radix (SR) and Coptidis Rhizoma (CR) have often been combined to cure type 2 diabetes mellitus (T2DM) in the clinical practice for over thousands of years, but their compatibility mechanism is not clear. Mitogen-activated protein kinase (MAPK) signaling pathway has been suggested to play a critical role during the process of inflammation, insulin resistance, and T2DM. This study was designed to investigate their compatibility effects on T2DM rats and explore the underlying mechanisms by analyzing the metabolic profiling and MAPK/PI3K/Akt signaling pathway. Methods The compatibility effects of SR and CR were evaluated with T2DM rats induced by a high-fat diet (HFD) along with a low dose of streptozocin (STZ). Ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was performed to discover potential biomarkers. The levels of pro-inflammatory cytokines; biochemical indexes in serum, and the activities of key enzymes related to glycometabolism in liver were assessed by ELISA kits. qPCR was applied to examine mRNA levels of key targets in MAPK and insulin signaling pathways. Protein expressions of p65; p-p65; phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K); phosphorylated-PI3K (p-PI3K); protein kinase B (Akt); phosphorylated Akt (p-Akt) and glucose transporter 2 (Glut2) in liver were investigated by Western blot analysis. Results Remarkably, hyperglycaemia, dyslipidemia, inflammation, and insulin resistance in T2DM were ameliorated after oral administration of SR and CR, particularly their combined extracts. The effects of SR, CR, low dose of combined extracts (LSC) and high dose of combined extracts (HSC) on pro-inflammatory cytokine transcription in T2DM rats showed that the MAPK pathway might account for the phenomenon with down-regulation of MAPK (P38 mitogen-activated protein kinases (P38), extracellular regulated protein kinases (ERK), and c-Jun N-terminal kinase (JNK)) mRNA, and protein reduction in p-P65. While mRNA levels of key targets such as insulin receptor substrate 1 (IRS1), PI3K, Akt2, and Glut2 in the insulin signaling pathway were notably up-modulated, phosphorylations of PI3K, Akt, and expression of Glut2 were markedly enhanced. Moreover, the increased activities of phosphoenolpyruvate carboxykinase (PEPCK), fructose-1,6-bisphosphatase (FBPase), glucose 6-phosphatase (G6Pase), and glycogen phosphorylase (GP) were highly reduced and the decreased activities of glucokinase (GK), phosphofructokinase (PFK), pyruvate kinase (PK), and glycogen synthase (GS) in liver were notably increased after treatment. Further investigation indicated that the metabolic profiles of plasma and urine were clearly improved in T2DM rats. Fourteen potential biomarkers (nine in plasma and five in urine) were identified. After intervention, these biomarkers returned to normal level to some extent. Conclusion The results showed that SR, CR, and combined extract groups were normalized. The effects of combined extracts were more remarkable than single herb treatment. Additionally, this study also showed that the metabonomics method is a promising tool to unravel how traditional Chinese medicines work.

Project description:Both plants and animals are living things made up of similar cells as well as organelles, and their essence of life is the same. However, plants face more environmental stress than animals and generate excessive reactive oxygen species (ROS), a group of small molecules that can harm proteins, necessitating distinctive metabolic processes. Secondary metabolites in plants are a group of chemical components that can eliminate ROS and can also exhibit medicinal properties; therefore, herbal medicines are often closely linked to the ecological significance of secondary metabolites. Why plants contain so many, not few, active medicinal ingredients is unknown. The root of Scutellaria baicalensis, a popular herbal medicine, is rich in various flavonoids with diverse structural features. Sodium hydrosulfite (Na2S2O4) can produce O˙-2 radicals and induce physical conditions under environmental stress. Using UHPLC-ESI-Q-TOF-MS/MS analysis, a total of 25 different compounds were identified in the roots of S. baicalensis between the Na2S2O4 groups and suitable conditions. Based on the results of the t-test (P<0.05) performed for the groups and ions with values of VIP ≥ 2, the most significantly different chemical markers with Na2S2O4 treatment were shikimic acid, citric acid, baicalin, wogonoside, baicalein, wogonin, 3,5,7,2',6'-pentahydroxyflavanone, 5,2',6'-trihydroxy-7,8-dimethoxy flavone, chrysin, eriodictyol, 5,8-dihydroxy-6,7 -dimethoxy flavone, skullcapflavone Ⅱ, and 5,7-dihydroxy-6,8,2',3'-tetrame thoxyflavone, and most of them were free flavonoids with many phenolic hydroxyl or methoxyl groups and characteristically high antioxidant activities. S. baicalensis roots modified their ability to eliminate ROS and maintained the equilibrium of ROS through the multitudinous biosynthesis and conversion of flavonoids, which is similar to the equilibrium established by an intricate buffer solution and perfectly explains the diversity and complexity of medicinal plant ingredients.

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Herbal formula, Scutellariae radix and Rhei rhizoma attenuate dimethylnitrosamine-induced liver fibrosis in a rat model.

Publications

Herbal formula, Scutellariae radix and Rhei rhizoma attenuate dimethylnitrosamine-induced liver fibrosis in a rat model.

Similar Datasets

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