Ultrasound-assisted optimisation of Cinnamomum cassia (L.) polyphenol extraction and their antidiabetic effects via AMPK – GLUT4 activation

Cinnamomum cassia (L.) polyphenols (CPs) exhibit diverse pharmacological activities. This study optimised ultrasound-assisted extraction (UAE) of CPs and investigated their potential antidiabetic mechanisms. Response surface methodology identified optimal extraction conditions, yielding 4.093% extraction efficiency. Non-targeted metabolomics identified 1-palmitoyl-sn-glycero-3-phosphocholine (LPC (16:0)) and 1-oleoyl-glycerophosphocholine as major identified components, accounting for 10.49% and 6.97%, respectively. In an insulin-resistant LO2 cell model, CPs significantly promoted glucose consumption and glycogen synthesis while inhibiting key gluconeogenic enzymes phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase). Furthermore, CPs upregulated superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) levels while decreasing malondialdehyde (MDA) production. CP exerts hypoglycaemic effects by activating the 5′-adenosine monophosphate-activated protein kinase (AMPK)-glucose transporter 4 (GLUT4) axis. These findings reveal the antidiabetic potential of CPs and their underlying molecular mechanisms, providing a theoretical basis for the bioactive role of this traditional Chinese medicine.