Therapeutic impact of the ethyl acetate extract of Tripterygium wilfordii Hook F on nephritis in NZB/W F1 mice

Xuelian Tao,Peter E Lipsky,Victoria Hoffmann,Nancy S Longo,Fred Fan

doi:10.1186/ar1879

Abstract

This study was designed to examine the potential use of the ethyl acetate (EA) extract of Tripterygium wilfordii Hook F (TwHF), a Chinese herbal medicine, in the treatment of systemic lupus erythematosus. A total of 48 28-week-old female NZB/W F1 mice were randomly divided into three groups and orally administered vehicle or the EA extract of TwHF at 18.25 mg/kg (EAlow) or 36.5 mg/kg (EAhigh) for 14 weeks. Proteinuria and serum anti-double-stranded (ds)DNA antibody titers were assayed before and after treatment. At the end of treatment, all animals were sacrificed and pathological changes in the kidneys were examined by observers blinded to the treatment regimens. Immunohistological studies were carried out on kidneys and spleens. At 28 weeks of age, proteinuria (>30 mg/dl) and anti-dsDNA antibodies were found in all mice in the three groups. Fourteen, sixteen and fifteen mice in the vehicle, EAlow and EAhigh groups, respectively, completed at least four weeks of treatment. At the end of treatment, the mean proteinuria of the EAlow and EAhigh groups was significantly less than that of the vehicle group and no different from proteinuria at the onset of treatment. Histological evidence of glomerulonephritis, glomerular deposition of IgG and complement 3 and cellular infiltration in the interstitium and perivascular regions were significantly less severe in the EA extract treated mice than in vehicle treated mice. Treatment with the EA extract significantly inhibited the progression of kidney disease in NZB/W F1 mice, though had no significant effect on the levels of anti-dsDNA antibody.

Highlights

The Chinese anti-rheumatic remedy Tripterygium wilfordii Hook F (TwHF) has been reported to be effective in the treatment of a variety of autoimmune diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and psoriasis [1,2]
Gu and colleagues [11] found that a water extract of TwHF ameliorated glomerulonephritis and prolonged survival in MRL-lpr/lpr mice, but only when therapy was begun before disease onset
No evidence was provided that the extract of BSA = bovine serum albumin; BUN = blood urea nitrogen; C3 = complement 3; ds = double stranded; EA = ethyl acetate; FITC = fluorescein isothiocyanate; HPLC = high-performance liquid chromatography; IL = interleukin; LD50 = lethal dose 50%; RA = rheumatoid arthritis; SLE = systemic lupus erythematosus; TwHF = Tripterygium wilfordii Hook F

Summary

Introduction

The Chinese anti-rheumatic remedy Tripterygium wilfordii Hook F (TwHF) has been reported to be effective in the treatment of a variety of autoimmune diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and psoriasis [1,2]. Gu and colleagues [11] found that a water extract of TwHF ameliorated glomerulonephritis and prolonged survival in MRL-lpr/lpr mice, but only when therapy was begun before disease onset. Consistent with this, Zhang and colleagues [12] reported improvement in survival, proteinuria, arthritis and lymphadenopathy in MRL-lpr/lpr mice treated with another TwHF preparation. No improvement in renal histology was noted Both of these studies suggest benefit in this model of murine lupus when treatment was begun before disease onset, the full extent of potential benefit was not established.

Methods

Results

Conclusion