Specialized metabolites from the Chinese liverwort Heteroscyphus coalitus (Hook.) Schiffn and their anti-inflammatory activity.

Four previously undescribed diterpenoids, ent-clerodanoids, coalitins A-C (1-3), an ent-abietanoid, coalisin A (5), and one 2-nor-ent-aromadendrane-type sesquiterpenoid, coalisin B (15), along with sixteen known compounds were isolated from the liverwort Heteroscyphus coalitus (Hook.) Schiffn. Interestingly, coalisin B (15), a norsesquiterpenoid featuring an unprecedented 2-nor-ent-aromadendrane skeleton different from the common natural series, was identified. Their structures were determined by NMR spectroscopic data analysis, high resolution electrospray ionization mass spectroscopy data and experimental electronic circular dichroism measurements. Subsequently, bioactivity assessments revealed that compounds 12, 17, and 20 exhibited potent NO inhibition in RAW 264.7 cells, with IC50 values of 21.35, 27.36 and 13.98 μM, respectively. Further mechanistic studies manifested that the potent anti-inflammatory activity of 12, 17, and 20 were precisely evidenced by their ability to downregulate the relative phosphorylation levels of NF-κB p65 and concurrently suppress the production of cytokines TNF-α, IL-6, and IL-1β.