Theabrownin from Dark Tea Ameliorates Insulin Resistance via Attenuating Oxidative Stress and Modulating IRS-1/PI3K/Akt Pathway in HepG2 Cells

Abstract

Dark tea has great potential in regulating glycolipid metabolism, and theabrownin (TB) is considered to be the characteristic and bioactive constituent of dark tea. This study evaluated the ability of TB1 (fermented for 7 days) and TB2 (fermented for 14 days) isolated from dark tea to reverse insulin resistance (IR) in HepG2 cells. The results indicated that TB significantly ameliorated oxidative stress by improving mitochondrial function. In addition, TB improved glycogen synthesis and glucose consumption, and inhibited gluconeogenesis and fatty acid synthesis, by regulating GSK3β (Glycogen synthase kinase 3β), G6Pase (Glucose-6-phosphatase), GCK (Glucokinase), PEPCK1 (Phosphoenolpyruvate carboxy kinase 1), SREBP-1C (sterol regulatory element-binding protein 1C), FASN (fatty acid synthase), and ACC (Acetyl-CoA carboxylase). Additionally, the results of Western blot and real-time PCR experiments demonstrated that TB modulated glucolipid metabolism through the IRS-1 (Insulin receptor substrate 1)/PI3K (phosphatidylinositol-3 kinase)/Akt (protein kinase B) signaling pathway. Treatment with the PI3K inhibitor demonstrated a favorable correlation between PI3K activation and TB action on glycolipid metabolism. Notably, we observed that TB2 had a greater effect on improving insulin resistance compared with TB1, which, due to its prolonged fermentation time, increased the degree of oxidative polymerization of TB.

Modulation of Gut Microbial Biomarkers and Metabolites in Cancer Management by Tea Compounds

“…TB is a microbial fermented polyphenol found in dark tea like Pu-erh tea and Fu Brick tea [ 73 , 74 ]. The health benefits of TB include preventing tumors, improving immunity, anti-inflammation, alleviating obesity and metabolic syndromes, and ability to improve gut microbiota [ 73 , 74 , 75 , 76 , 77 , 78 ]. TB demonstrated anti-tumorigenesis effects on CRC in the AOM/DSS model [ 33 ].…”

'Nine Steaming Nine Sun‐drying' processing enhanced properties of Polygonatum kingianum against inflammation, oxidative stress and hyperglycemia

“…50 Consistently, the reduction of G6pase and GDK3⊎ in cells often accompanies the positive regulation of the transport and metabolism of glucose. 51 A global view of the compounds-target-pathway network was constructed (Fig. 6(A-C); Supporting Information, Tables S4 and S5) and the top ten pathways and top five key compounds with higher degree of connectivity in each network were presented.…”