Isoindolines and phthalides from the rhizomes of Ligusticum chuanxiong and their relaxant effects on the uterine smooth muscle. (June 2022)

• Record Type: Journal Article
• Authors: Liu, Juan; Feng, Rui; Dai, Ou; Ni, Hong; Liu, Lu-Si; Shu, Hong-Zhen; Lu, Yan; Peng, Cheng; Xiong, Liang
• Is Part Of: Phytochemistry. Volume 198(2022)
• Publication Date: 2022-06
• Subjects: Ligusticum chuanxiong -- Apiaceae -- Isoindoline alkaloids -- Phthalides -- Relaxant effect on uterine smooth muscle -- [Ca2+]i; Botanical chemistry -- Periodicals; Biochemistry -- Periodicals; Botany -- Periodicals; Chimie végétale -- Périodiques; 572.2
• DOI: 10.1016/j.phytochem.2022.113159
• Languages: English
• ISSNs: 0031-9422

Abstract

Abstract: Three undescribed isoindoline alkaloids, (+)-( R )-3-butyl-3-ethoxyisoindolin-1-one, (+)-(3 S, 6 S, 7 R )-3-butyl-6, 7-dihydroxy-3-methoxy-4, 5, 6, 7-tetrahydroisoindolin-1-one, and (−)-(3 R, 6 S, 7 R )-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 Ca 2+ influx and intracellular Ca 2+ release were assessed using high-KCl solution-induced and oxytocin-induced uterine smooth muscle contraction in a Ca 2+ -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 Ca 2+ influx and intracellular Ca 2+ release. Graphical abstract: Three previously undescribed isoindoline alkaloids and nine known phthalides were isolated from Ligusticum chuanxiong Hort. (Apiaceae). All the tested phthalides showed inhibitory effects on oxytocin-induced uterine smooth muscle contraction. Image 1 Highlights: Three undescribed isoindolines were isolated from Ligusticum chuanxiong. Most of the isolated phthalides have relaxant effects on uterine smooth muscle. Riligustilide had the greatest effect. Riligustilide inhibited extracellular Ca 2+ influx and intracellular Ca 2+ release.