Damsin and neoambrosin: Two sesquiterpene lactones with affinity and different activity for PPAR and TRPA1 receptors.

Ambrosia maritima L. (family Asteraceae) is an annual herb widely distributed throughout the Mediterranean region and Africa. The herb is employed in folk medicine for the treatment of many ailments. Herein, we report a comprehensive investigation of the diverse biological potential of two sesquiterpene lactones, damsin and neoambrosin, isolated from Ambrosia maritima. 1D and 2D NMR and HR-ESI-MS/MS were employed to characterize the chemical structures of both compounds. In order to identify biological targets of both compounds we investigated their potential affinity for peroxisome proliferator-activated receptors (PPARs) and transient receptor potential (TRP) channels, which are pleiotropic classes of receptors implicated in essential functions of the body. This was investigated using a luciferase assay and a calcium fluorometric assay. A carbonic anhydrase inhibition assay was also performed using stopped flow CO ₂ hydrase spectrophotometric assay. Our analysis revealed that unlike damsin, neoambrosin showed a selective partial agonist effect on PPARγ receptors and TRPA1 channels. Its binding mode was investigated through in silico analysis. Both compounds showed no affinity for the tested carbonic anhydrases. Overall, our study details the chemical properties of neoambrosin and damsin and highlights neoambrosin as novel, cost-effective partial agonist of PPARɣ and TRPA1 receptors despite additional in vivo studies are needed to elucidate its biological and pharmacological properties.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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