Abstract:

Objective To investigate the inhibitory effects of different Ginkgo biloba leaf extract (GBE) ingredients on the proliferation and extracellular matrix (ECM) accumulation of high glucose-treated mesangial cells,and to clarify their mechanisms. Methods The high glucose-treated mesangial cells (HBZY-1) were given GBE,total flavonoids,total ginkgolide,total flavonoids hydrolyzate,quercetin,kaempferol,isorhamnetin,ginkgolide A,B,and ginkgolide C; the concentrations were 0(high glucose control group),3.125,6.250,12.500,25.000 and 50.000 mg·L^-1,meanwhile low glucose control group was set up. The cell proliferation was detected by MTT assay. The high glucose-treated mesangial cells were given GBE,total flavonoids,total ginkgolide,ginkgolide A,ginkgolide B,and ginkgolide C;the concentrations were 0(high glucose control group),0.05,0.50,5.00,50.00 mg·L^-1,meanwhile low glucose control group was set up. The levels of fibronectin(FN) and type Ⅳ collagen (Col Ⅳ) were detected by ELISA method. Results The MTT results showed that compared with high glucose control group,the proliferation activity of mesangial cells in 50.00 mg·L^-1 GBE group was decreased significantly (P<0.01);the proliferation activities of mesangial cells in 25.00 and 50.00 mg·L^-1 total flavonoids group were decreased significantly(P<0.05 or P<0.01);the proliferation activities of mesangial cells in all quercetin,kaempferol,isorhamnetin and total flavonoids hydrolyzate groups were decreased significantly (P<0.01);the proliferation activity of mesganial cells in 50.00 mg·L^-1 ginkgolide C group was decreased significantly (P<0.01). The ELISA results showed that compared with high glucose control group,the levels of Col Ⅳand FN in 5.00 and 50.00 mg·L^-1 GBE groups were decreased significantly (P<0.01),and the FN level in 0.50 mg·L^-1 GBE group was decreased significantly (P<0.05);the Col Ⅳ levels in 0.50,5.00,and 50.00 mg·L^-1 total flavonoids groups were decreased significantly(P<0.05 or P<0.01);the Col Ⅳand FN levels in all total ginkgolide groups had no obviously differences except 50.00 mg·L^-1ginkgolide C group (P<0.05 or P<0.01);the FN level in 50 mg·L^-1 ginkgolide C group was decreased significantly(P<0.05). Conclusion GBE can inhibit the high glucose-induced proliferation only in the high concentration (50 mg·L^-1) and inhibit the high glucose-induced mesangial cell ECM accumulation in the low concentration (0.50-25.00 mg·L-1);the total flavonoids plays a major role in the inhibition of cell proliferation and ECM accumulation,and the total ginkgolide has no significant effect;the inhibitory effect of aglycones on mesangial cell proliferation is much stronger than that of glucoside.

Key words: Ginkgo biloba leaf extract, diabetic nephropathy, total flavonoids of ginkgo biloba, ginkgolide, aglycones, glucoside