Scutellariae Radix and Coptidis Rhizoma Improve Glucose and Lipid Metabolism in T2DM Rats via Regulation of the Metabolic Profiling and MAPK/PI3K/Akt Signaling Pathway

• Published in: International journal of molecular sciences 2018-11, Vol.19 (11), p.3634
• Main Authors: Cui, Xiang, Qian, Da-Wei, Jiang, Shu, Shang, Er-Xin, Zhu, Zhen-Hua, Duan, Jin-Ao
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; Adipocytes; AKT protein; AKT2 protein; Animals; Atrophy; Biomarkers; Blood Glucose - metabolism; c-Jun protein; Compatibility; Coptis chinensis; Cytokines; Cytokines - metabolism; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - pathology; Disease; Down-regulation; Drug dosages; Drugs, Chinese Herbal - pharmacology; Drugs, Chinese Herbal - therapeutic use; Dyslipidemia; Dyslipidemias - blood; Dyslipidemias - drug therapy; Enzymes; Extracellular signal-regulated kinase; Gene expression; Glucokinase; Glucose; Glucose - metabolism; Glucose transporter; Glycogen; Glycogen phosphorylase; Glycogen synthase kinase 3; Glycogens; High fat diet; Hyperglycemia; Hyperglycemia - blood; Hyperglycemia - drug therapy; Inflammation; Inflammation - pathology; Insulin; Insulin - metabolism; Insulin Resistance; Investigations; Lipid metabolism; Lipid Metabolism - drug effects; Lipids; Liquid chromatography; Liver; Liver - drug effects; Liver - metabolism; Male; Mass spectrometry; Metabolic Networks and Pathways - drug effects; Metabolism; Metabolites; Metabolomics; Metformin - pharmacology; Metformin - therapeutic use; Mitogen-Activated Protein Kinases - metabolism; Oral administration; Phosphatidylinositol 3-Kinases - metabolism; Principal Component Analysis; Proteins; Proto-Oncogene Proteins c-akt - metabolism; Pyruvate kinase; Quadrupoles; Rats, Sprague-Dawley; Scutellaria baicalensis - chemistry; Signal transduction; Signal Transduction - drug effects; Transcription factors
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms19113634

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. 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. 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), phosphofructokinas