Bioactive compounds from Cornus officinalis fruits and their effects on diabetic nephropathy.
The fruit of Cornus 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.


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 anti-diabetic 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 anti-diabetic 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 μg/mL; and loganin (3) and its derivatives (1 and 2) could significantly inhibit the expression of FN and IL-6 at concentration of 10 μM, respectively.


CONCLUSIONS
The results suggested that loganin and its derivatives were the active compounds in Cornus officinalis fruit (Shanzhuyu) on diabetic nephropathy. This study further supported the traditional use of Shanzhuyu to treat diabetic nephropathy and related kidney diseases.
Anhui Key Laboratory of Bioactivity of Natural Products, School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei 230032, PR China.
Wei
W
Ma
School of Life Sciences, Anhui University, 3 Feixi Road, Hefei 230039, PR China.
Kai-Jin
KJ
Wang
School of Life Sciences, Anhui University, 3 Feixi Road, Hefei 230039, PR China.
Chen-Shu
CS
Cheng
School of Life Sciences, Anhui University, 3 Feixi Road, Hefei 230039, PR China.
Guo-qing
GQ
Yan
Anhui Key Laboratory of Bioactivity of Natural Products, School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei 230032, PR China.
Wei-Li
WL
Lu
Anhui Key Laboratory of Bioactivity of Natural Products, School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei 230032, PR China.
Jing-Fang
JF
Ge
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650204, PR China. Electronic address: yxcheng@mail.kib.ac.cn.
Yong-Xian
YX
Cheng
Anhui Key Laboratory of Bioactivity of Natural Products, School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei 230032, PR China. Electronic address: ln0110@sina.com.
Ning
N
Li
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D024141:Collagen Type IV / Q000037:antagonists & inhibitors / Q000378:metabolism; D029768:Cornus; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000378:metabolism; D005353:Fibronectins / Q000037:antagonists & inhibitors / Q000378:metabolism; D005638:Fruit; D015850:Interleukin-6 / Q000378:metabolism; D050527:Mesangial Cells / Q000187:drug effects* / Q000378:metabolism; D064209:Phytochemicals / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D000093242:Interleukin-6 Inhibitors
D024141:Collagen Type IV; D005353:Fibronectins; D015850:Interleukin-6; D064209:Phytochemicals; D010936:Plant Extracts; D000093242:Interleukin-6 Inhibitors
7-α-morroniside (PubChem CID: 21593530); Caffeic acid (PubChem CID: 689043); Cornus officinalis fruit; Cornuside (PubChem CID: 131348); Diabetic nephropathy; Iridoid glucoside; Kaempferol-3-O-β-d-rutinoside (PubChem CID: 12313332); Loganic acid (PubChem CID: 89640); Loganin; Loganin (PubChem CID: 87691); Quercetin (PubChem CID: 5280343); Secoxyloganin (PubChem CID: 162868); Tachioside (PubChem CID: 11962143)