A Rational Combination of Cyclocarya paliurus Triterpene Acid Complex (TAC) and Se-Methylselenocysteine (MSC) Improves Glucose and Lipid Metabolism via the PI3K/Akt/GSK3β Pathway

Cyclocarya paliurus (CP) contains triterpene acids that can improve glucose and lipid metabolism disorders. However, controlling the composition and content of these active ingredients in CP extracts is challenging. The main active components in CP triterpene acids, including ursolic acid (UA), oleanolic acid (OA), and betulinic acid (BA), exhibit antihyperglycemic and antihypertensive effects. The response surface methodology was utilized to design and optimize the ratio of UA, OA, and BA based on the inhibition rate of pancrelipase and α-amylase. The proportional mixture of UA, OA, and BA resulted in the formation of a complex known as Cyclocarya paliurus triterpenoid acid (TAC). Se-methylselenocysteine (MSC), a compound with various physiological functions such as antioxidant properties and tumor inhibition, has been used in combination with TAC to form the TAC/MSC complex. Our data demonstrate that TAC/MSC improved palmitic acid (PA)-induced insulin resistance in HepG2 cells through activating the phosphoinositide 3-kinase (PI3K) /protein kinase B (AKT)/glycogen synthase kinase 3 beta (GSK3β) pathway. Moreover, TAC/MSC effectively improved hyperglycemia, glucose intolerance, insulin resistance, and lipid metabolism disorder in mice with type 2 diabetes mellitus (T2DM), attenuated hepatic steatosis, and reduced oxidative stress to alleviate T2DM characteristics.