Cyclotides Isolated from an Ipecac Root Extract Antagonize the Corticotropin Releasing Factor Type 1 Receptor

摘要

FIGURE 1. Analytical profile of ipecac cyclotide extract. (A) Image of a representative Carapichea ipecacuanha root [photograph by courtesy and with permission of Orlando Vargas Ramírez (Vargas, 2017), Organization for Tropical Studies, Costa Rica]. (B) Analytical reversed-phase liquid chromatography (RP-HPLC) of crude cyclotide-enriched extract of C. ipecacuanha, with magnification of cyclotide fractions (inset), performed using linear gradients as described in the section “Materials and Methods.” (C,D) Matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectra of (C) the hydrophobic cyclotide-rich fraction and (D) the hydrophilic non-cyclotide containing fraction from the crude extract. (E) Inhibition of human CRF-induced CRE-specific luciferase activity by ipecac cyclotide extracts. The data presented are mean ± SD of five separate experiments performed in triplicate. (F) The ipecac extract inhibits human CRF response in a concentration-dependent manner with an IC50 of 2.0 μg mL-1. Masses labeled in the spectra refer to monoisotopic [M+H]+.