Baicalein, a major component of the root of Oroxylum indicum (L.) Kurz (Bignoniaceae), inhibits phosphodiesterase 5 and vasodilates isolated pulmonary arteries through endothelium-independent mechanisms

Abstract

Oroxylum indicum (L.) Kurz root has been traditionally used as an aphrodisiac. This study aimed to elucidate the phosphodiesterase (PDE) 5 inhibition and vasodilatory effects of O. indicum root extract and its main constituent. LC-QTOF-MS/MS analysis identified twenty constituents within the extract, including baicalein, biochanin A, and chrysin, detected in both positive and negative modes. HPLC analysis confirmed baicalein as the major constituent of O. indicum root extract. The extract exhibited potential for PDE5 inhibition, with an IC₅₀ value of 1.96 μg/mL. Among the three compounds, biochanin A demonstrated the highest PDE5 inhibition, with an IC₅₀ value of 6.16 μM, followed by baicalein (IC₅₀ = 20.54 μM) and chrysin (IC₅₀ = 42.18 μM). The vascular effects and mechanisms of O. indicum extract (0.01–300 μg/mL) and compounds (10⁻¹¹–10⁻⁶ M) were evaluated in rat-isolated pulmonary artery (PA) and aorta. Both O. indicum extract and baicalein exhibited potent vasodilatory effects, with greater efficacy in the PA compared to the aorta. E_max values for PA versus aorta were 84.8 % versus 24.8 % (p < 0.001) for O. indicum extract and 85.3 % versus 31.9 % (p < 0.001) for baicalein. O. indicum-induced PA relaxation was endothelium-dependent, involving eNOS activation, COX pathways, and EDHF production. Conversely, baicalein-induced PA relaxation was endothelium-independent, mediated by inhibition of K_v channels, intracellular calcium release, and blockade of alpha-1 adrenergic receptors. Taken together, these findings expand the biological profile of O. indicum root and highlight baicalein as a promising candidate for cardiovascular disease treatment.