Pentacyclic Triterpenoids from Astilbe rivularis that Enhance Glucose Uptake via the Activation of Akt and Erk1/2 in C2C12 Myotubes

• Published in: Journal of natural products (Washington, D.C.) Vol. 78; no. 5; pp. 1005 - 1014
• Main Authors: Han, Joo-Hui, Zhou, Wei, Li, Wei, Tuan, Pham Quoc, Khoi, Nguyen Minh, Thuong, Phuong Thien, Na, MinKyun, Myung, Chang-Seon
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society and American Society of Pharmacognosy 22.05.2015; Amer Chemical Soc
• Subjects: Biological Transport; Chemistry, Medicinal; Glucose - metabolism; Glucose Transporter Type 4 - metabolism; Insulin - pharmacology; Life Sciences & Biomedicine; Mitogen-Activated Protein Kinase 3 - metabolism; Molecular Structure; Muscle Fibers, Skeletal - metabolism; Nuclear Magnetic Resonance, Biomolecular; Pentacyclic Triterpenes - chemistry; Pentacyclic Triterpenes - isolation & purification; Pentacyclic Triterpenes - pharmacology; Pharmacology & Pharmacy; Phosphorylation; Plant Roots - chemistry; Plant Sciences; Proto-Oncogene Proteins c-akt - metabolism; Saxifragaceae - chemistry; Science & Technology; Vietnam; Vietnam; PATHWAYS; TRANSPORT; LIPID-METABOLISM; ACID; THERAPY; INSULIN-RESISTANCE; PROTEIN-KINASE; PHOSPHATASE; ROSIGLITAZONE; INHIBITOR
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/np5009174

Glucose uptake into insulin-sensitive tissues is important for the regulation of blood glucose. This study has investigated whether the pentacyclic triterpenoids substituted with a carboxylic acid at the C-27 position isolated from Astilbe rivularis can enhance glucose uptake and subsequently to also examine their underlying molecular mechanisms. The structure of the new pentacyclic triterpenoid 1 was assigned by spectroscopic data interpretation. To evaluate the activity of compounds 1 and 2, glucose uptake and glucose transporter 4 (GLUT4) translocation were measured in C2C12 myotubes. The C-27-carboxylated triterpenoids 1 and 2 significantly increased basal and insulin-stimulated glucose uptake and GLUT4 translocation to plasma membrane. Both compounds stimulated the phosphorylation of insulin receptor substrate-1 (IRS-1), protein kinase B (Akt), and extracellular signal-regulated kinase 1/2 (Erk1/2). Pretreatment with the Akt inhibitor triciribine or the Erk1/2 inhibitor U0126 decreased the ability of both compounds to enhance basal- and insulin-stimulated glucose uptake and stimulate GLUT4 translocation. These results indicate that compounds 1 and 2 activated both the IRS-1/Akt and Erk1/2 pathways and subsequently stimulated GLUT4 translocation, leading to enhanced glucose uptake. Thus, these observations suggest that C-27-carboxylated-pentacyclic triterpenoids may serve as scaffolds for development as agents for the management of blood glucose levels in disease states such as diabetes.