Multi-omics profiling reveals organ-specific anti-inflammatory metabolites and biosynthetic regulation in Lindera aggregata taproot-bark

Lindera aggregata is a highly valued traditional Chinese medicinal herb, with its tuberous roots (tubers) traditionally regarded as the principal medicinal organ due to their richness in bioactive metabolites. However, the pharmacological activities, metabolic composition, and underlying regulatory mechanism governing the biosynthesis of bioactive compounds in the non-tuberous roots (taproots), remain unclear. In this study, we systematically compared the anti-inflammatory activities and metabolomic profiles of L. aggregata leaves, taproots, and tubers. Multi-omics integration revealed tissue-specific distribution patterns and biosynthetic pathways of key anti-inflammatory isoquinoline alkaloids (IQAs). The underlying regulatory mechanisms were elucidated using transient expression assays and molecular approaches. Surprisingly, the taproot displayed superior anti-inflammatory activity, which was closely associated with the accumulation of 16 specific IQAs, particularly (S)-tetrahydrocolumbamine and isoboldine. IQAs biosynthesis was found to be more active in taproots, and the upregulation of key biosynthetic genes ( La6OMTs , LaNCSs , LaC4'OMT ) caused the accumulation, leading to high medicinal bioactivities of taproots. Notably, the transcription factor (TF) LaGL3 was identified as a direct activator of La6OMT2 expression. Spatial metabolite mapping using mass spectrometry imaging further revealed that alkaloid accumulation was primarily localized to the root bark. This spatial specificity correlated with the high expression levels of both biosynthetic genes and TFs in the bark tissue. These findings establish that the taproot and root bark, which are discarded during processing, possess significant medicinal value. Collectively, our results uncover the superior anti-inflammatory potential of L. aggregata taproots and elucidate the regulatory framework governing IQA biosynthesis and accumulation, thereby providing a foundation for the optimized utilization of L. aggregata resources, the development of high-quality medicinal products. • Both taproots and tubers of Lindera aggregata exhibit potent anti-inflammatory effects. • Isoboldine and (S)-tetrahydrocolumbamine show potent anti-inflammatory activity. • Isoquinoline alkaloids accumulate primarily in the root bark of Lindera aggregata . • LaGL3 enhances isoquinoline alkaloid accumulation by activating La6OMT-2 expression.