Mechanistics Studies on the Antidiabetic Activity of Oleanolic Acid
Jose M. Castellano, Teresa Delgado, Ángeles Guinda, Mirela Rada, Pilar Gutiérrez-Adanez, Jose A. Cayuela
Instituto de la Grasa – CSIC, Seville (Spain)

Oleanolic acid (OA) (3β-hydroxy-olean-12-en-28-oic acid), a natural component of many plant food and medicinal herbs, is endowed with a wide range of pharmacological properties, including an antidiabetic effect. This last action of OA results from a complex and multifactorial mechanism which includes the post-prandial control of glycemia, improvement of the insulin response, preservation of functionality and survival of β-cell, and protection against diabetes complications. In this communication, as integrated in a more general study on the molecular basis of the antidiabetic action of this triterpene, we show that OA exerts a low-moderate antioxidant activity in vitro, but plays a significant inhibition of enteric enzymes involved in digestion of complex carbohydrates. 
Type-2 diabetes is now recognized as phenotype of mitochondrial dysfunction, where impaired oxidative activity accumulates superoxide and other ROS. The resultant oxidative stress injures tissues by promoting DNA fragmentation, protein crosslinking, membrane phospholipids peroxidation, and activation of stress pathways. Our results support that rather than a chemical direct action, the major contribution of OA as antidiabetic agent is derived from its interaction with important transduction pathways. The management of type-2 diabetes requires an integrated approach, which includes the early intervention to prevent or delay the disease progression, and the use of therapies to control glycemia and lipidemia in its late stages. In this sense, the use of functional foods or drugs containing oleanolic acid is, undoubtedly, an interesting via.