Chemical constituents and anti-renal fibrosis activity of the resin from Pinus yunnanensis.

Thirty-nine compounds were obtained from the resin of Pinus yunnanensis, including five previously undescribed diterpenoids, designated pinuskesiols G-K (1-5). On the basis of spectroscopic methods, NMR chemical shifts calculations and experimental electron circular dichroism (ECD) measurements, their planar structures and stereochemical configurations were elucidated. Pinuskesiol G (1) exhibits an uncommon lactone moiety in the C-ring, whereas pinuskesiol H (2) features a rare B-ring-opened framework. Pinuskesiols I (3) and J (4) are distinguished by the replacement of the C-13 isopropyl substituent with an acetonyl group. In vitro anti-renal fibrotic evaluation showed that compounds 1-5 exhibited pronounced activity in NRK-52E and NRK-49F cells, significantly attenuating TGF-β1-induced upregulation of fibronectin, collagen I, and α-SMA expression. Further mechanistic studies revealed that these compounds could downregulate TGF-β1-induced p-Smad2/3 expression. On this basis, the in vitro activities of known compounds 6-39 were then assessed, enabling a preliminary discussion of their structure-activity relationships.