Biscaesalmins A and B from Caesalpinia minax, highly oxidized dimeric cassane diterpenoids as interleukin-1β inhibitors

Abstract To search naturally occurring interleukin-1β (IL-1β) inhibitors, biscaesalmins A (1) and B (2), two highly oxidized dimeric cassane diterpenoids with newly formed alicyclic skeleton, have been isolated from the traditional Chinese medicine Kushilian (Caesalpinia minax). Their full structures were determined by comprehensive spectroscopic analysis and quantum chemical TD-DFT (time-dependent density functional theory) calculation. Biosynthetically, 1 and 2 were formed via an intermolecular [4 + 2] Diels-Alder cycloaddition of two monomers, affording an additional six-membered carbon ring linkage. Compounds 1 and 2 inhibited nitric oxide production on lipopolysaccharide-stimulated THP-1 macrophages, with IC50 values being at 1.20 ± 0.23 and 2.30 ± 0.15 μmol/L, respectively. Furthermore, compound 1 inhibited NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) inflammasome-mediated IL-1β production and blocked the migration of macrophages towards adipocyte conditioned medium. Biscaesalmins A and B might be candidates for treating inflammation-related metabolic diseases.