Chuanxiongdiolides R4 and R5, phthalide dimers with a complex polycyclic skeleton from the aerial parts of Ligusticum chuanxiong and their vasodilator activity

[Display omitted] •Three novel phthalide dimers were isolated from the aerial parts of L. chuanxiong.•Compounds 1, 3, 4, 5, and 6 showed significant vasodilation effects.•Compounds 1, 3, and 5a showed the obvious Cav1.2 block activity.•The structure-activity relationship of phthalide dimers in vasodilation was discussed. Chuanxiongdiolides R4-R6 (1–3), three novel phthalide dimers featuring two classes of unreported monomeric units (ligustilide/senkyunolide A and ligustilide/neocnidilide) with an unprecedented linkage style (3a,7′/7a,7′a), were isolated from the aerial parts of Ligusticum chuanxiong, together with three pairs of enantiomeric phthalide dimers [(−)/(+)-4a/4b, 5a/5b, and 6a/6b]. The bioassays revealed that compounds 1, 3, 4, 5, and 6 showed significant vasodilation effects, and the mechanism may be attributed to Cav1.2 activation blockade. Based on the established compounds library, the structure activity relationship of the phthalides was proposed. Our findings afford possible leads for developing new vasodilator against cardiovascular and cerebrovascular diseases such as hypertension and ischemic stroke.