Ribemansides A and B, TRPC6 Inhibitors from Ribes manshuricum That Suppress TGF-β1-Induced Fibrogenesis in HK-2 Cells.

Two new acylated β-hydroxynitrile glycosides, ribemansides A (1) and B (2), were isolated from the aerial parts of Ribes manshuricum. Their structures were elucidated by comprehensive spectroscopic analysis. Ribemansides A and B inhibited transforming growth factor β1 (TGF-β1)-induced expression of α-smooth muscle actin, fibronectin release, and changes in cell morphology in the human proximal tubular epithelial cell line (human kidney-2, HK-2). Further biological evaluation demonstrated that both 1 and 2 inhibit the activity of canonical transient receptor potential cation channel 6 (TRPC6), with IC50 values of 24.5 and 25.6 μM, respectively. The antifibrogenic effect of these compounds appears to be mediated through TRPC6 inhibition, since the TRPC6 inhibitor, SAR7334, also suppressed TGF-β1-induced fibrogenesis in HK-2 cells.