Abietane-Type Diterpenoids from the Resin of Pinus yunnanensis and Their Potential Anti-Renal Fibrosis Activities.

Chronic kidney disease (CKD) has emerged as a pressing global public health concern, making the identification of renal fibrosis inhibitors a key research focus. In this study, seven undescribed abietane-type diterpenoids, pinusyunins A-G (1, 2, 4, and 7-10) and three known analogues (3, 5, and 6), were isolated from Pinus yunnanensis resin, which were identified by spectroscopic analyses and quantum computational chemistry methods. Biological evaluation showed that all the isolates exhibited inhibitory activity against the expression of collagen I, fibronectin, and α-SMA in transforming growth factor-β1 (TGF-β1)-induced NRK-52E and NRK-49F cells. Specifically, compounds 1-10 reduced the expression of α-SMA at 40 μM in both cell lines, while compounds 6-8 and 10 decreased the expression of these three markers at 40 μM in both cell lines with the potency of compound 10 superior to the others in α-SMA inhibition in NRK-52E cells. Variations in activity are associated with differences in substituents at the C-13 position. Further studies demonstrated that these abietane-type diterpenoids block the TGF-β/Smad signaling pathway by inhibiting the phosphorylation of Smad2/3. In particular, compounds 1, 3, 6, and 7 suppressed only p-Smad3 other than p-Smad2, indicating their specificity. The research on these abietane-type diterpenoids provides novel candidate molecules and a scientific underpinning for developing anti-renal fibrosis drugs.