Computationally-Assisted Discovery and Assignment of a New Class of 6/6/5/5 Fused-Ring Diterpene Acting as Pregnane X Receptor Ligands from .

We report here the orchestration of molecular ion networking (MoIN) and a set of computationally assisted structural elucidation approaches in the discovery and assignment of a new class of rearranged 4,5--abietane diterpenoids including serra A (), which possesses an unusual 6/6/5/5 fused-ring skeleton system, together with two previously unreported diterpenoids serras B-C (-) and five known compounds were isolated from (). The structures were elucidated by spectroscopic analysis in conjunction with computationally assisted structure elucidation tools. , serras A-C (-) bind well to PXR, suggesting their potential role in reducing inflammation. The results of serra A () with hPXR demonstrated agonist activity with an EC value of 15 μM. Serra A (), graciliflorin F (), gerardianin C (), 11,12,15-trihydroxy-8,11,13-abietatrien-7-one (), rabdosin D (), and 15-hydroxysalprionin () exhibited promising anti-inflammatory activities in lipopolysaccharide (LPS)-induced RAW 267.4 cells, and their inhibition rates on NO production were more than 65% at 10 μM.