Facultad de Química, Departamento de Farmacia, Universidad Nacional Autónoma de México, Ciudad Universitaria, Ciudad de México, Mexico.
Laboratorio de Farmacología, Programa Institucional en Biomedicina Molecular, Escuela, Nacional de Medicina y Homeopatía del Instituto Politécnico Nacional, Ciudad de México, Mexico.
Drug Dev Res. 2019 Aug;80(5):585-594. doi: 10.1002/ddr.21535. Epub 2019 Apr 8.
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 (mm ) was determined. 3α-hydroxymasticadienonic acid and DLG as individual compounds showed a gastroprotective effect against indomethacin-induced gastric damage (p < .05). The effective dose (ED ) 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 ED 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).
本研究旨在评估分别从植物短序崖姜和川芎中分离得到的 3α-羟基齐墩果烯酸和地奥司明（DLG）之间的药效学相互作用，采用吲哚美辛诱导的胃损伤模型，并评价它们在该模型中的单独胃保护作用。雄性 Wistar 大鼠口服给予 3α-羟基齐墩果烯酸、DLG 或 3α-羟基齐墩果烯酸-DLG（固定比例 1:1、1:3 和 3:1）混合物。30 分钟后，单次口服给予吲哚美辛（30mg/kg）诱导胃损伤。3 小时后，测定胃损伤（mm）。3α-羟基齐墩果烯酸和 DLG 作为单独的化合物对吲哚美辛诱导的胃损伤均表现出胃保护作用（p<.05）。各化合物的有效剂量（ED）值分别为 3α-羟基齐墩果烯酸 6.96±1.25mg/kg 和 DLG 2.63±0.37mg/kg。进行的等比分析表明，组合表现出超相加相互作用，因为实验 ED 值（Zexp）低于理论加性剂量值（Zadd；p<.05）。我们的结果表明 3α-羟基齐墩果烯酸和 DLG 之间存在超加（协同）相互作用，并且在吲哚美辛诱导的胃损伤模型中两种化合物具有胃安全性，提示它们在未来作为减少与非甾体抗炎药（NSAIDs）慢性使用相关的胃损伤的策略具有潜力。
