TY - JOUR
T1 - Pharmacodynamic interaction of 3α-hydroxymasticadienonic acid and diligustilide against indomethacin-induced gastric damage in rats
AU - Pineda-Peña, Elizabeth A.
AU - Meza-Pérez, Dulce G.
AU - Chávez-Piña, Aracely E.
AU - Velázquez-Moyado, Josué A.
AU - Tavares-Carvalho, José C.
AU - Navarrete Castro, Andrés
N1 - Publisher Copyright:
© 2019 Wiley Periodicals, Inc.
PY - 2019
Y1 - 2019
N2 - The aims of the study were to evaluate the pharmacodynamic interaction between 3α-hydroxymasticadienonic acid and diligustilide (DLG), isolated from the plants Amphiptherygium adstringens and Ligusticum porteri, respectively, using the indomethacin-induced gastric injury model, as well as their individual gastroprotective efficacy in this model. Male Wistar rats were orally administered with 3α-hydroxymasticadienonic acid, DLG or the mixture of 3α-hydroxymasticadienonic acid-DLG (at a fixed-ratio combination of 1:1, 1:3, and 3:1). Thirty minutes later, the gastric damage was induced by a single oral dose of indomethacin (30 mg/kg). Three hours later, the gastric injury (mm2) was determined. 3α-hydroxymasticadienonic acid and DLG as individual compounds showed a gastroprotective effect against indomethacin-induced gastric damage (p <.05). The effective dose (ED50) values for each compound were 6.96 ± 1.25 mg/kg for 3α-hydroxymasticadienonic acid and 2.63 ± 0.37 mg/kg for DLG. The isobolographic analysis performed showed that the combination exhibited super-additive interaction as the experimental ED50 values (Zexp) were lower than theoretical additive dose values (Zadd; p <.05). Our results identify the super-additive (synergist) interaction between 3α-hydroxymasticadienonic acid and DLG and the gastric safety of both compounds in the indomethacin—induced gastric injury model, suggesting their potential in the future as a strategy to decrease the gastric damage associated to the chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs).
AB - The aims of the study were to evaluate the pharmacodynamic interaction between 3α-hydroxymasticadienonic acid and diligustilide (DLG), isolated from the plants Amphiptherygium adstringens and Ligusticum porteri, respectively, using the indomethacin-induced gastric injury model, as well as their individual gastroprotective efficacy in this model. Male Wistar rats were orally administered with 3α-hydroxymasticadienonic acid, DLG or the mixture of 3α-hydroxymasticadienonic acid-DLG (at a fixed-ratio combination of 1:1, 1:3, and 3:1). Thirty minutes later, the gastric damage was induced by a single oral dose of indomethacin (30 mg/kg). Three hours later, the gastric injury (mm2) was determined. 3α-hydroxymasticadienonic acid and DLG as individual compounds showed a gastroprotective effect against indomethacin-induced gastric damage (p <.05). The effective dose (ED50) values for each compound were 6.96 ± 1.25 mg/kg for 3α-hydroxymasticadienonic acid and 2.63 ± 0.37 mg/kg for DLG. The isobolographic analysis performed showed that the combination exhibited super-additive interaction as the experimental ED50 values (Zexp) were lower than theoretical additive dose values (Zadd; p <.05). Our results identify the super-additive (synergist) interaction between 3α-hydroxymasticadienonic acid and DLG and the gastric safety of both compounds in the indomethacin—induced gastric injury model, suggesting their potential in the future as a strategy to decrease the gastric damage associated to the chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs).
KW - 3α-hydroxymasticadienonic acid
KW - NSAIDs
KW - diligustilide
KW - gastric injury
KW - isobolographic analysis
UR - http://www.scopus.com/inward/record.url?scp=85063988847&partnerID=8YFLogxK
U2 - 10.1002/ddr.21535
DO - 10.1002/ddr.21535
M3 - Artículo
C2 - 30957263
SN - 0272-4391
VL - 80
SP - 585
EP - 594
JO - Drug Development Research
JF - Drug Development Research
IS - 5
ER -