Abrus precatorius Leaf Extract Stimulates Insulin-mediated Muscle Glucose Uptake: In vitro Studies and Phytochemical Analysis.

Diabetes mellitus, linked with insulin resistance and hyperglycaemia, is a leading cause of mortality. Glucose uptake through glucose transporter type 4, especially in skeletal muscle, is crucial for maintaining euglycaemia and is a key pathway targeted by antidiabetic medication. Abrus precatorius is a medicinal plant with demonstrated antihyperglycaemic activity in animal models, but its mechanisms are unclear.This study evaluated the effect of a 50% ethanolic (v/v) A. precatorius leaf extract on (1) insulin-stimulated glucose uptake and (2) related gene expression in differentiated C2C12 myotubes using rosiglitazone as a positive control, and (3) generated a comprehensive phytochemical profile of A. precatorius leaf extract using liquid chromatography-high resolution mass spectrometry to elucidate its antidiabetic compounds. A. precatorius leaf extract significantly increased insulin-stimulated glucose uptake, and insulin receptor substrate 1 and Akt substrate of 160 kDa gene expression; however, it had no effect on glucose transporter type 4 gene expression. At 250 µg/mL A. precatorius leaf extract, the increase in glucose uptake was significantly higher than 1 µM rosiglitazone. Fifty-five phytochemicals (primarily polyphenols, triterpenoids, saponins, and alkaloids) were putatively identified, including 24 that have not previously been reported from A. precatorius leaves. Abrusin, precatorin I, glycyrrhizin, hemiphloin, isohemiphloin, hispidulin 4'-O-ß-D-glucopyranoside, homoplantaginin, and cirsimaritin were putatively identified as known major compounds previously reported from A. precatorius leaf extract. A. precatorius leaves contain antidiabetic phytochemicals and enhance insulin-stimulated glucose uptake in myotubes via the protein kinase B/phosphoinositide 3-kinase pathway by regulating insulin receptor substrate 1 and Akt substrate of 160 kDa gene expression. Therefore, A. precatorius leaves may improve skeletal muscle insulin sensitivity and hyperglycaemia. Additionally, it is a valuable source of bioactive phytochemicals with potential therapeutic use for diabetes.

The effects of pioglitazone and rosiglitazone on liver function in hypothyroid rats.

OBJECTIVES: This study aimed to investigate the antioxidant effect of rosiglitazone (ROG) and pioglitazone (POG) on oxidative damage and dysfunction of hepatic tissue in hypothyroid rats. METHODS: The male rats were classified into six groups: (1) Control; (2) Hypothyroid, (3) Hypothyroid-POG 10, (4) Hypothyroid-POG 20, (5) Hypothyroid-ROG 2, and (6) Hypothyroid-ROG 4. To induction hypothyroidism in rats, propylthiouracil (PTU) (0.05 %w/v) was added to drinking water. In groups 2-6, besides PTU, the rats were also intraperitoneal administrated with 10 or 20 mg/kg POG or 2 or 4 mg/kg ROG for six weeks. Finally, after deep anesthesia, the blood was collected to measure the serum biochemical markers and hepatic tissue was separated for biochemical oxidative stress markers. RESULTS: Administration of PTU significantly reduced serum thyroxin concentration, total thiol levels, activity of superoxide dismutase (SOD) and catalase (CAT) enzymes, and increased serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (Alk-P) and malondialdehyde (MDA) in the liver. Additionally, our results showed that prescription of POG or ROG for six weeks to hypothyroid rats resulted in an improvement in liver dysfunction (decrease in serum levels of AST, ALT, and ALK-P) through reducing oxidative damage in hepatic tissue (increase in CAT, SOD, or total thiols and decrease in MDA levels). CONCLUSIONS: The findings of the present study presented that the IP administration of POG and ROG for six weeks improves liver dysfunction induced by hypothyroidism in juvenile rats by reducing oxidative damage.

Essential oil from Fructus Alpiniae zerumbet ameliorates vascular endothelial cell senescence in diabetes by regulating PPAR-γ signalling: A 4D label-free quantitative proteomics and network pharmacology study.

ETHNOPHARMACOLOGICAL RELEVANCE: Vascular endothelial cell senescence is associated with cardiovascular complications in diabetes. Essential oil from Fructus Alpiniae zerumbet (Pers.) B.L.Burtt & R.M.Sm. (EOFAZ) has potentially beneficial and promising diabetes-related vascular endothelial cell senescence-mitigating effects; however, the underlying molecular mechanisms remain unclear. AIM OF THE STUDY: To investigate the molecular effects of EOFAZ on vascular endothelial cell senescence in diabetes. MATERIALS AND METHODS: A diabetes mouse model was developed using a high-fat and high-glucose diet (HFD) combined with intraperitoneal injection of low-dose streptozotocin (STZ, 30 mg/kg) and oral treatment with EOFAZ. 4D label-free quantitative proteomics, network pharmacology, and molecular docking techniques were employed to explore the molecular mechanisms via which EOFAZ alleviates diabetes-related vascular endothelial cell senescence. A human aortic endothelial cells (HAECs) senescence model was developed using high palmitic acid and high glucose (PA/HG) concentrations in vitro. Western blotting, immunofluorescence, SA-ß-galactosidase staining, cell cycle, reactive oxygen species (ROS), cell migration, and enzyme linked immunosorbent assays were performed to determine the protective role of EOFAZ against vascular endothelial cell senescence in diabetes. Moreover, the PPAR-γ agonist rosiglitazone, inhibitor GW9662, and siRNA were used to verify the underlying mechanism by which EOFAZ combats vascular endothelial cell senescence in diabetes. RESULTS: EOFAZ treatment ameliorated abnormal lipid metabolism, vascular histopathological damage, and vascular endothelial aging in diabetic mice. Proteomics and network pharmacology analysis revealed that the differentially expressed proteins (DEPs) and drug-disease targets were associated with the peroxisome proliferator-activated receptor gamma (PPAR-γ) signalling pathway, a key player in vascular endothelial cell senescence. Molecular docking indicated that the small-molecule compounds in EOFAZ had a high affinity for the PPAR-γ protein. Western blotting and immunofluorescence analyses confirmed the significance of DEPs and the involvement of the PPAR-γ signalling pathway. In vitro, EOFAZ and rosiglitazone treatment reversed the effects of PA/HG on the number of senescent endothelial cells, expression of senescence-related proteins, the proportion of cells in the G0/G1 phase, ROS levels, cell migration rate, and expression of pro-inflammatory factors. The protective effects of EOFAZ against vascular endothelial cell senescence in diabetes were aborted following treatment with GW9662 or PPAR-γ siRNA. CONCLUSIONS: EOFAZ ameliorates vascular endothelial cell senescence in diabetes by activating PPAR-γ signalling. The results of the present study highlight the potential beneficial and promising therapeutic effects of EOFAZ and provide a basis for its clinical application in diabetes-related vascular endothelial cell senescence.