Distinctive Cassane Diterpenoids Corroborated Biogenetic Evolutionary Process from Caesalpinia mimosoides with Anti-renal Fibrosis Activity

Comprehensive Summary Eighteen diterpenoids were isolated from the seeds of Caesalpinia mimosoides, including four extremely infrequent cassane diterpenes, together with nine new and five known structures. Compounds 7 and 8 represent the first examples of cassane diterpenoids fused with a ketone carbonyl and a ternary oxygen ring at C-4, respectively. Compounds 9 and 10 possess a rare five-member ring in cassane diterpenes. Intriguingly, these isolated components are a clue to the fact that there are lower and higher levels in the plant secondary metabolites, demonstrating the evolution of secondary metabolism of C. mimosoides. All the isolated compounds were tested for their anti-renal fibrosis activity against TGF-beta 1 induced NRK-52E cell model. The mRNA levels of fibrosis marker alpha-SMA, E-cadherin, Collagen I were tested by qRT-PCR. The data showed compounds 6 and 9 exhibited the best anti-renal fibrosis activity and provided preliminary structure-activity relationships.