TY - JOUR
T1 - Structure-activity relationship study of acyclic terpenes in blood glucose levels
T2 - Potential α-Glucosidase and Sodium Glucose Cotransporter (SGLT-1) Inhibitors
AU - Valdes, Miguel
AU - Calzada, Fernando
AU - Mendieta-Wejebe, Jessica
N1 - Publisher Copyright:
© 2019 by the authors.
PY - 2019
Y1 - 2019
N2 - Twelve terpenoids were evaluated in the treatment of type 2 diabetes mellitus: seven monoterpenes (geranyl acetate (1), geranic acid (2), citral (3), geraniol (4), methyl geranate (5), nerol (6), and citronellic acid (7)), three sesquiterpenes (farnesal (8), farnesol (9), and farnesyl acetate (10)), one diterpene (geranylgeraniol (11)), and one triterpene (squalene (12)) were selected to carry out a study on normoglycemic and streptozotocin-induced diabetic mice. Among these, 2, 3, 7, 8, 9, and 10 showed antihyperglycemic activity in streptozotocin-induced diabetic mice. They were then selected for evaluation in oral sucrose and lactose tolerance tests (OSTT and OLTT) as well as in an oral glucose tolerance test (OGTT). In the OSTT and OLTT, compounds 3, 7, 8, 9, and 10 showed a reduction in postprandial glucose peaks 2 h after a sucrose or lactose load (comparable to acarbose). In the case of the OGTT, 2, 7, 8, 9, and 10 showed a reduction in postprandial glucose peaks 2 h after a glucose load (comparable to canagliflozin). Our results suggest that the control of postprandial hyperglycemia may be mediated by the inhibition of disaccharide digestion, such as sucrose and lactose, and the regulation of the absorption of glucose. The first case could be associated with an∞/-glucosidase inhibitory effect and the second with an inhibition of the sodium-glucose type 1 (SGLT-1) cotransporter. Finally, five acyclic terpenes may be candidates for the development and search for new α-glucosidase and SGLT-1 cotransporter inhibitors.
AB - Twelve terpenoids were evaluated in the treatment of type 2 diabetes mellitus: seven monoterpenes (geranyl acetate (1), geranic acid (2), citral (3), geraniol (4), methyl geranate (5), nerol (6), and citronellic acid (7)), three sesquiterpenes (farnesal (8), farnesol (9), and farnesyl acetate (10)), one diterpene (geranylgeraniol (11)), and one triterpene (squalene (12)) were selected to carry out a study on normoglycemic and streptozotocin-induced diabetic mice. Among these, 2, 3, 7, 8, 9, and 10 showed antihyperglycemic activity in streptozotocin-induced diabetic mice. They were then selected for evaluation in oral sucrose and lactose tolerance tests (OSTT and OLTT) as well as in an oral glucose tolerance test (OGTT). In the OSTT and OLTT, compounds 3, 7, 8, 9, and 10 showed a reduction in postprandial glucose peaks 2 h after a sucrose or lactose load (comparable to acarbose). In the case of the OGTT, 2, 7, 8, 9, and 10 showed a reduction in postprandial glucose peaks 2 h after a glucose load (comparable to canagliflozin). Our results suggest that the control of postprandial hyperglycemia may be mediated by the inhibition of disaccharide digestion, such as sucrose and lactose, and the regulation of the absorption of glucose. The first case could be associated with an∞/-glucosidase inhibitory effect and the second with an inhibition of the sodium-glucose type 1 (SGLT-1) cotransporter. Finally, five acyclic terpenes may be candidates for the development and search for new α-glucosidase and SGLT-1 cotransporter inhibitors.
KW - Acyclic terpenes
KW - Antihyperglycemic activity
KW - Diabetes mellitus
UR - http://www.scopus.com/inward/record.url?scp=85074712047&partnerID=8YFLogxK
U2 - 10.3390/molecules24224020
DO - 10.3390/molecules24224020
M3 - Artículo
C2 - 31698833
AN - SCOPUS:85074712047
SN - 1420-3049
VL - 24
JO - Molecules
JF - Molecules
IS - 22
M1 - 4020
ER -