Isoindolines and phthalides from the rhizomes of Ligusticum chuanxiong and their relaxant effects on the uterine smooth muscle

Abstract

Three undescribed isoindoline alkaloids, (+)-(R)-3-butyl-3-ethoxyisoindolin-1-one, (+)-(3S,6S,7R)-3-butyl-6,7-dihydroxy-3-methoxy-4,5,6,7-tetrahydroisoindolin-1-one, and (-)-(3R,6S,7R)-3-butyl-6,7-dihydroxy-3-methoxy-4,5,6,7-tetrahydroisoindolin-1-one, along with nine known phthalides were isolated from a water decoction of the rhizomes of Ligusticum chuanxiong using chromatographic methods. Their structures and absolute configurations were determined by extensive spectroscopic analyses and ECD data calculations. The relaxant effects of the isolated compounds on uterine contractions induced by oxytocin were investigated using a rat uterine smooth muscle contraction model. Furthermore, the effects of riligustilide on extracellular Ca²⁺ influx and intracellular Ca²⁺ release were assessed using high-KCl solution-induced and oxytocin-induced uterine smooth muscle contraction in a Ca²⁺-free balanced salt solution. The results showed that all the tested phthalides had inhibitory effects on oxytocin-induced uterine smooth muscle contraction. Riligustilide, a phthalide dimer, was the most active. Further examinations indicated that riligustilide reduced uterine smooth muscle contraction by inhibiting extracellular Ca²⁺ influx and intracellular Ca²⁺ release.

Keywords: Apiaceae; Isoindoline alkaloids; Ligusticum chuanxiong; Phthalides; Relaxant effect on uterine smooth muscle; [Ca(2+)](i).