Spasmolytic Activity of a Lipidic Extract from Sabal serrulata Fruits: Further Study of the Mechanisms Underlying this Activity

Abstract

The mechanisms involved in the spasmolytic effect of a lipidic extract from Sabal serrulata fruits were investigated. The extract relaxed vanadate-induced contractions on rat uterus incubated in a calcium free solution (EC₅₀ = 11.41 ± 1.38 µg/ml). The modification of the effect by a cyclooxygenase inhibitor (indomethacin), a protein kinase A inhibitor (TPCK), calcium modifying drugs, and drugs interfering with transcription and protein synthesis has been assayed. The effect was unmodified by a 3 µM concentration of indomethacin, (EC₅₀ = 8.77 ± 1.28 vs 11.41 ± 1.38 µg/ml) and a 5 µg/ml concentration of the transcription inhibitor, actinomycin D, (EC₅₀ = 8.23 ± 2.19 vs 11.41 ± 1.38 µg/ml). The inhibitor of intracellular calcium mobilization TMB-8 (0.1 mM), the Na⁺/Ca⁺⁺ exchanger inhibitor amiloride (0.1 mM), the calcium chelator BAPTA-AM (50 µM), the PKA inhibitor TPCK (10 µM), and the protein synthesis inhibitor cycloheximide (10 µg/ml) significantly shifted to the right the dose-response curve of the extract (EC₅₀ = 17.83 ± 1.87 µg/ml, 18.61 ± 2.50 µg/ml, 35.28 ± 9.13 µg/ml, 33.99 ± 3.07 µg/ml, and 27.31 ± 4.93 µg/ml, respectively, vs 11.41 ± 1.38 µg/ml). These results suggest that the effect of the lipidic extract from S. serrulata fruits could be partially due to Na⁺/Ca⁺⁺ exchanger activation and interference with intracellular calcium mobilization, and point to cAMP as a possible mediator. Moreover, protein synthesis seems to be involved in the spasmolytic activity.

Key words

Spasmolytic action - Sabal serrulata - Palmae - cAMP - calcium - protein synthesis