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 (<b>1</b>, <b>2</b>, <b>4</b>, and <b>7</b>-<b>10</b>) and three known analogues (<b>3</b>, <b>5</b>, and <b>6</b>), were isolated from <i>Pinus yunnanensis</i> 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 <i>α</i>-SMA in transforming growth factor-<i>β</i>1 (TGF-<i>β</i>1)-induced NRK-52E and NRK-49F cells. Specifically, compounds <b>1</b>-<b>10</b> reduced the expression of <i>α</i>-SMA at 40 μM in both cell lines, while compounds <b>6</b>-<b>8</b> and <b>10</b> decreased the expression of these three markers at 40 μM in both cell lines with the potency of compound <b>10</b> superior to the others in <i>α</i>-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-<i>β</i>/Smad signaling pathway by inhibiting the phosphorylation of Smad2/3. In particular, compounds <b>1</b>, <b>3</b>, <b>6</b>, and <b>7</b> 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.