Three pairs of new enantiomeric adenine alkaloids, (+)/(-)-liguadenines A-C [(+)/(-)-1-3], were isolated from the rhizome of Ligusticum chuanxiong Hort. The structures and absolute configurations of these compounds were determined using spectroscopic data, single-crystal X-ray diffraction, and electronic circular dichroism analyses. To the best of our knowledge, com-pounds (+)-1 and (-)-1 are the first hybrid phthalide-adenines to be ever reported. The linkage between the phthalide and adenine units in these compounds forms a rare 5-oxa-1-azaspiro[3,4] octane moiety. Analyses of the anti-inflammatory activities of the isolated compounds show that (+)/(-)-1 and (+)-3 exhibit significant inhibitory activity against LPS-induced TNF-a and IL-6 production in RAW264.7 cells. RT-qPCR analysis confirms that the most active compound, (+)-3, exerts anti-inflammatory activity by downregulating the mRNA expressions of TNF-a and IL-6 in the cells.(c) 2023 The Author(s). Published by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).