Discovered cassane diterpenoids from Caesalpinia mimosoides lam. Exhibited anti-renal fibrosis activity via regulating TGF-β1/Smads signaling pathway.

Renal fibrosis is marker and common pathway of progressive chronic kidney disease (CKD), eventually leading to renal dysfunction. So far, there is still a lack of secure drugs and effective therapeutic strategies. Caesalpinia mimosoides is an edible Dai folk medicinal plant and exhibits good effect on inducing diuresis to alleviate edema, hinting that C. mimosoides might possess the potential to treat kidney disease. Thus, this study aimed to search potential active ingredients for the treatment of kidney disease. Based on the biological activity-guided separation strategy, ten undescribed cassane diterpenoids (1-10) including six furan lactone-types (1-6), two furan-types (7-8), and two nocassane-types (9-10), together with five known cassane derivatives (11-15) were discovered from C. mimosoides, among of them, compounds 1, 2 and 3, 11 to be two pairs of epimers at asymmetric center C-14. The structures including absolute configuration were unambiguously elucidated by detailed spectroscopic methods complemented with X-ray diffractions and ECD calculations. The anti-renal fibrosis activity of isolated diterpenoids were evaluated in TGF-β1-induced NRK-52E cells. Compound 14 exerted excellent renal fibrosis inhibitory activity by regulating the expression of EMT markers (E-cadherin, α-SMA) and ECM components (collagen I, fibronectin). The underlying mechanistic study revealed that 14 suppressed renal fibrosis via inhibiting TGF-β1/Smads signaling pathway. This work reported the potential of C. mimosoides in the treatment of kidney disease, and the systematically disclosed the anti-renal fibrosis activity of cassane diterpenoids, implying the cassane diterpenoids to be the promising new type anti-renal fibrosis drug precursors in future. Additionally, our work also substantiated the potential of C. mimosoides as a prospective natural source of bioactive compounds in functional food and pharmaceutical industries.