The green leaves and roots of Lycopus lucidus var. hirtus are highly valuable as edible and medicinal resources, which can be consumed alone as a decoction or in combination with other foods. Nevertheless, there remains a notable gap in the systematic and scientific exploration of its functional constituents. Through a bioactivity-guided fractionation approach using a BV-2 cell model to monitor antineuroinflammatory activity, 19 abietane diterpenoids were successfully isolated from Lycopus hirtus. Notably, in hirtuses A-D (1-4), four new diterpenoids were elucidated via ECD calculations and single-crystal X-ray diffraction analyses. Hirtuse A (1) was a highly modified nor-diterpenoid with an unprecedented 6/6/6/5/4 pentacyclic ring skeleton and possesses an uncommon spiro5.4 ring system constructed by one γ-lactonic ring and one oxetane unit. Additionally, the proposed biosynthetic pathways of 1 were also deduced. In terms of the antineuroinflammatory activity, the crude extract of L. hirtus presented strong activity. The newly identified compound 4 demonstrated significant efficacy by modulating the NF-κB signaling pathway. A comprehensive understanding of the phytochemical composition, along with activity evaluation of crude and abietane diterpenoids from L. hirtus, could facilitate their targeted selection and development.
Li et al. (Tue,) studied this question.