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.
