Gnaphaliin A and Gnaphaliin B Identified as Active Principles of Gnaphalium liebmannii Sch. B.p. ex Klatt (Asteraceae) with Tracheal Smooth Muscle Relaxant Properties

Abstract

Inflorescences of Gnaphalium liebmannii Sch. B.p. ex Klatt, commonly known as „Gordolobo“, is the most important remedy in Mexican traditional medicine to treat respiratory diseases, including asthma. Using a bio-guided fractionation of the n-hexane extract of this plant, following the relaxant effect on guinea pig tracheal smooth muscle, the flavones 5,7-dihydroxy-3,8-dimethoxyflavone (1) and 3,5-dihydroxy-7,8-dimethoxyflavone (2) were identified as the active relaxant compounds. Both 1 and 2 have been described as gnaphaliin in the past; The EIMS data, NMR experiments for both compounds, and X-ray diffraction analysis for 1, provided structural information to suggest that 1 and 2 should be named gnaphaliins A and B, respectively. Gnaphaliin A and gnaphaliin B induced relaxation on guinea pig trachea with EC50 values of 181.58±2.22µM and 128.36±1.88µM respectively. Both flavones were more potent to relax the guinea pig trachea than enoximone, rolipram and aminophylline, but they were less potent than sildenafil. Gnaphaliin A and B were also effective to inhibit cAMP (IC50=120.8±26µM and 72.1±11µM, respectively) and cGMP (IC50=2.9±0.3µM and 6.4±2µM, respectively) degradation by PDE, showing preference to inhibit the degradation of cGMP, with the follow activity order: sildenafil > rolipram > gnaphaliin A > gnaphaliin B > aminophylline > IBMX, enoximone. In addition, both flavones inhibited the flux of extracellular calcium in guinea-pig trachea. Acknowledgements: This work was supported by grant of Dirección General de Asuntos del Personal Académico DGAPA-UNAM IN 205008 and CONACYT 82613. F. Rodríguez-Ramos acknowledges fellowship from CONACYT 131381.