Anti-inflammatory, antioxidant, and gaso-protective mechanism of 3α-hydroxymasticadienoic acid and diligustilide combination on indomethacin gastric damage

Elizabeth Arlen Pineda-Peña, Alejandra Orona-Ortiz, Josué Arturo Velázquez-Moyado, José Carlos Tavares-Carvalho, Aracely Evangelina Chávez-Piña, José Luis Balderas-López, Andrés Navarrete

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    The co-administration of 3α-hydroxymasticadienoic acid (3α-OH MDA) and diligustilide (DLG) generates a synergist gastroprotective effect on indomethacin-induced gastric damage. However, the related protective activities of the compounds alone (or in combination) remain unclear. In the present study, we evaluated the anti-inflammatory and antioxidative activities, as well as the potential modulation of important gasotransmitters of each compound individually and in combination using the indomethacin-induced gastric damage model. Male Wistar rats were treated orally with the 3α-OH MDA, DLG, or their combination (at a fixed ratio of 1:1, 1:3, and 3:1) 30 min before the generation of gastric mucosal lesions with indomethacin (30 mg/kg, p.o.). Three hours later, the gastric injury (mm2) was determined. Results from these experiments indicate, in addition to maintaining basal levels of PGE2, the gastroprotective effect of the pre-treatment with 3α-OH MDA (70%), DLG (81%), and their combination (72%) which was accompanied by significant decreases in leukocyte recruitment, as well as decreases in TNF-α and LTB4 gastric levels (p < 0.05). We also found that the pre-treatment maintains the basal antioxidant enzyme activities (SOD) and gastric NO and H2S production even in the presence of indomethacin (p < 0.05). In conclusion, when 3α-OH MDA-DLG is given at a 1:1 combination ratio, the gastroprotective effect and the inflammatory, antioxidant, and gaso-modulation properties are not different from those of treatments using the maximum doses of each compound, revealing that this combination produces promising results for the treatment of gastric ulcers.

    Original languageEnglish
    JournalNaunyn-Schmiedeberg's Archives of Pharmacology
    StateAccepted/In press - 1 Jan 2020



    • 3α-Hydroxymasticadienoic acid
    • Anti-inflammatory
    • Antioxidant
    • Diligustilide
    • Gasotransmitters
    • Gastric ulcer
    • Indomethacin

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