Lariciresinol Displays Anti‐Diabetic Activity through Inhibition of α‐Glucosidase and Activation and Enhancement of Insulin Signaling

Abstract

Scope: The aim of this study is to investigate the antidiabetic effect of lariciresinol (LSR) in C2C12 myotubes and streptozotocin (STZ)-induced diabetic mice. Methods and results: To investigate antidiabetic potential of LSR, 𝜶-glucosidase inhibitory assay, molecular docking, glucose uptake assay, western blot assay on antidiabetic biomarkers are performed. STZ-induced diabetic model is used for in vivo study by calculating oral glucose tolerance test, histochemical examination, and glycogen assay. LSR inhibits 𝜶-glucosidase activity with an IC 50 value of 6.97 ± 0.37 µM and acts as a competitive inhibitor with an inhibitory constant (Ki) value of 0.046 µM. In C2C12 cells, LSR activates insulin signaling leading to glucose transporter 4 (GLUT4) translocation and augmented glucose uptake. Furthermore, in Streptozotocin (STZ)-treated diabetic mice, 3 weeks of oral LSR administration (10 mg kg −1 ) considerably decrease blood glucose levels, while increasing insulin levels in an oral glucose tolerance test, improve pancreatic islet size, increase GLUT4 expression, and significantly enhance insulin signaling in skeletal muscle. LSR treatment also activates glycogen synthase kinase 3𝜷 (GSK-3𝜷) resulting in improved glycogen content. Conclusion: The findings indicate a potential usefulness for oral LSR in the management and prevention of diabetes by enhancing glucose homeostasis.

Terpenoid-Rich Extract of Dillenia indica L. Bark Displays Antidiabetic Action in Insulin-Resistant C2C12 Cells and STZ-Induced Diabetic Mice by Attenuation of Oxidative Stress

“…As shown ( Figure 6 C), diabetic control animals (G2) exhibited extensive islet shrinkage and lower numbers of islet cells in the pancreas when compared with control animals (G1), whereas G4 animals (TRDI; 150 mg/kg) exhibited islet cells, normal acini cells, and few pancreatic cell regeneration foci. As excess glucose is stored as glycogen in the liver and skeletal muscle [ 30 ], we examined glycogen levels in skeletal muscle in the STZ-induced diabetic mice. As indicated ( Figure 6 D,E), glycogen levels in the skeletal muscle had increased significantly in G4 when compared with G2 and G3.…”

“…DM is a multifaceted metabolic condition with several negative health implications. To combat this, extensive methods and therapeutics are used to improve glycemic control such as insulin sensitizers, insulin secretagogues, and prandial glucose regulators [ 30 ]. However, some drugs elicit serious side effects in patients with poor tolerance.…”

Metabolite Profiling of Microwave-Assisted Sargassum fusiforme Extracts with Improved Antioxidant Activity Using Hybrid Response Surface Methodology and Artificial Neural Networking-Genetic Algorithm

“…Proteins were separated according to their molecular weight using 10% SDS gel electrophoresis, followed by the transfer of bands to nitrocellulose membranes for 2 h. A 5% bovine serum albumin (BSA) was added to the membrane and incubated overnight at 4 °C with the first antibody, followed by incubation with a secondary antibody (anti-goat IgG). Bands were detected using a chemiluminescence system (PerkinElmer) [ 29 ].…”

Biological activities, identification, method development, and validation for analysis of polyphenolic compounds in Nymphaea rubra flowers and leaves by UHPLC‐Q‐cIM‐TOF‐MS and UHPLC‐TQ‐MS

“…α-Glucosidase breaks down oligosaccharides into monosaccharides, which are taken into the bloodstream from the colon. 4,5 Therefore, α-glucosidase inhibitors can effectively reduce postprandial hyperglycaemia after a mixedcarbohydrate diet and treat DM. Mounting evidence revealed that many plant species' therapeutic properties, such as antidiabetic, anticancer, antiaging, and antimelanin activities, are attributed to antioxidant polyphenolics.…”

“…Additionally, α‐glucosidase is a crucial enzyme for diabetes mellitus (DM). α‐Glucosidase breaks down oligosaccharides into monosaccharides, which are taken into the bloodstream from the colon 4,5 . Therefore, α‐glucosidase inhibitors can effectively reduce postprandial hyperglycaemia after a mixed‐carbohydrate diet and treat DM.…”