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Tripterine is one of the major active components isolated from the traditional Chinese herb Tripterygium wilfordii Hook. f. Previous studies have shown that tripterine inhibits not only humoral and cellular immune responses but also the inflammatory response.1
This study aimed at exploring the inhibitory effects of tripterine on lupus nephritis. We studied the effect of tripterine in (NZB×W)F1 mice, who spontaneously develop autoimmune disease characterised by the production of dsDNA antibodies and the development of a severe immune complex glomerulonephritis, like in human lupus nephritis.2,3 The dsDNA antibodies are thought to have a role in the pathogenesis of mouse lupus-like nephritis.4 Raised levels of circulating anti-dsDNA antibodies often precede the development of nephritis.5,6
(NZB×W)F1 female mice, 2 months of age at the start of the experiment, were used in these studies. All animals were housed at constant temperature and fed a standard diet. The mice were evaluated for proteinuria every two weeks using the Coomassie blue G dye binding assay.7 After starting treatment all mice were housed in metabolic cages, and 24 hour urinary protein was collected for determination of basal urinary protein excretion levels. Levels >3 mg/day during the subsequent follow up were considered abnormal.8 Blood was collected from the ophthalmic venous plexa for determination of the packed cell volume, and the serum was stored at –20°C; serum anti-dsDNA antibody levels were measured by enzyme linked immunosorbent assay (ELISA)9 before treatment and then every two weeks. Twenty four hour urine samples were collected for determination of basal urinary protein excretion. The (NZB×W)F1 mice were randomly allocated to one of three groups to evaluate the therapeutic effect of tripterine on survival of the animals. Group A animals were untreated; groups B and C were given weekly intraperitoneal injections of tripterine 3 mg/kg wt and 6 mg/kg wt, respectively. The experiment was continued for 20 weeks.
We found that tripterine reduced the urinary protein excretion. Before treatment, animals in both groups B and C had similar concentrations of 24 hour urine protein. Untreated lupus mice (group A) at 6 weeks of age had an increased concentration of 24 hour urine protein. The mean (SD) urinary protein excretion was significantly reduced in tripterine treated groups (B and C) in comparison with the control group A (mean (SD) 0.43 (0.09) and 0.38 (0.13) v 14.89 (5.11) μg/min, p<0.001). There was no significant difference in proteinuria between groups B and C after eight weeks (0.53 (0.15) v 0.50 (0.19) μg/min).
The levels of serum anti-dsDNA autoantibodies were evaluated every two weeks during the study (table 1). Different doses of tripterine suppressed the serum level of anti-dsDNA antibodies at different stages.
In untreated animals a rise in the level of serum dsDNA antibodies preceded the change of proteinuria at 2–4 weeks.
Our preliminary study indicates that tripterine greatly reduces the amount of urine protein excretion, suppressing the formation of serum anti-dsDNA antibodies. It ameliorates the clinical symptoms of the (WZB×) F1 mice, improves their survival rate, and has a definite protective effect on lupus nephritis. These results suggest that clinical studies should be carried out to explore the exciting possibility that tripterine might be used in the treatment of human lupus.
This study was supported by grant 97401910 item from the Shanghai Science and Technology Committee Foundation.
We thank Professor De-Chen Zhang, Department of Pharmacology, Institute of Material Medica, Fudan University, for providing the tripterine.
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