Inhibitory effect of Tripterygium wilfordii multiglycoside on increased glomerular albumin permeability in vitro

Abstract

Background. Tripterygium wilfordii Hook F is a medicinal plant used for the treatment of glomerulonephritis in China. We studied the effect of Tripterygium wilfordii multiglycoside (TWG) on glomerular albumin permeability (P(albumin)) in vitro. Methods. Isolated rat glomeruli were incubated with protamine (600 μg/ml) for 30 min, or with human recombinant tumour necrosis factor (TNF-α, 0.4 ng/ml), superoxide (10 units/ml), or serum from a focal segmental glomerular sclerosis (FSGS) patient for 10 min at 37°C. TWG, 1 mg/ml, was added in parallel tubes to study the effect on P(albumin). Control glomeruli were incubated under identical conditions. The albumin reflection coefficient (σ(albumin)) was calculated from the change in glomerular volume in response to an applied oncotic gradient. Convectional permeability (P(albumin)) was calculated as (1-σ(albumin)). Results, Compared with controls, protamine increased the P(albumin) of glomeruli (0.83 ± 0.05, n = 25 vs 0.18 ± 0.03, n = 20); pretreatment with TWG blocked this effect (0.13 ± 0.04, n = 25). TNF-α also increased the P(albumin) (0.79 ± 0.04, n = 24 vs 0.04 ± 0.07, n = 19); preincubation with TWG blocked this effect (0.03 ± 0.09, n = 24). P(albumin) of glomeruli incubated with xanthine and xanthine oxidase, resulting in the production of superoxide, also increased as compared to controls (0.85 ± 0.04, n = 15 vs 0.08 ± 0.05, n = 14); TWG blocked this effect as well (0.21 ± 0.08, n = 14). FSGS serum also increased P(albumin) of glomeruli significantly (0.88 ± 0.02, n = 49 vs 0.00 ± 0.02, n = 49); preincubation with TWG blocked this effect (0.05 ± 0.07, n = 30). TWG by itself had no effect on P(albumin) (0.19 ± 0.10, n = 15). Conclusions. Our results show that TWG blocks protamine, TNF-α, superoxide, and FSGS serum-mediated increase in glomerular albumin permeability in vitro. We conclude that reduction of proteinuria by Tripterygium wilfordii multiglycoside in various kinds of glomerular diseases in vivo might be due to protection of the glomerular filtration barrier.