Bioactive compounds from Comus officinalis fruits and their effects on diabetic nephropathy

Ethnoparmacological relevance: The fruit of Comus officinalis, called Shanzhuyu, a traditional medicine in China, is used for the treatment of kidney diseases, including diabetic nephropathy. The aim of this study is to investigate the anti-diabetic nephropathy activity of Shanzhuyu and the active compounds in the fruit. Materials and methods: The air dried fruit of Cornus officinalis was extracted in 80% EtOH, the obtained residue was fractioned on D101 resin column eluted with H2O/EtOH solution to get five crude fractions (fr. A-E). The anti-diabetic nephropathy activity of fractions (fr. A-E) was evaluated.in vitro by inhibiting the expression of collagen IV (Col V), fibronectin (FN) and IL-6 in high-glucose-induced mesangial cells. By preliminary bio-assay screenings, repeated column chromatography on fraction B-D led the isolation of 22 compounds, whose structures were determined by extensive spectroscopic analysis, and the antidiabetic nephropathy activity of the isolated compounds was also evaluated. Results: Two new iridoid glucosides, logmalicids A and B (1 and 2), together with 20 known compounds (3-22) were isolated from the extract of Shanzhuyu under the bioassay-guided screenings. The antidiabetic nephropathy activity assay displayed that fractions A, D and E could significantly inhibit the production of Col IV; fractions A and C could significantly inhibit the expression of FN and IL-6 in the high-glucose-stimulated mesangial cells at concentration of 50 mu g/mL; and loganin (3) and its derivatives (1 and 2) could significantly inhibit the expression of FN and IL-6 at concentration of 10 mu M, respectively. Conclusions: The results suggested that loganin and its derivatives were the active compounds in Comus officinalis fruit (Shanzhuyu) on diabetic nephropathy. This study further supported the traditional use of Shanzhuyu to treat diabetic nephropathy and related kidney diseases. (c) 2014 Published by Elsevier Ireland Ltd.