Effectiveness and safety of tripterygium glycosides tablet for lupus nephritis: a systematic review and Meta-analysis.

OBJECTIVE: To investigate the effectiveness and safety of tripterygium glycosides (TG) tablet for the treatment of Lupus nephritis (LN). METHODS: Several databases were systematically searched including PubMed, Embase, Cochrane, Wiley, China National Knowledge Infrastructure Database, SinoMed and Wanfang Library till June 20, 2020. Revman5.3 was utilized to analyze the data according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement. RESULTS: In total, 8 randomized controlled trials involving 583 participants were identified. Meta-analyses showed that, compared with glucocorticoids (GC) alone, the combination with TG tablet provided a statistically significant improvement in total remission (TR) ( = 1.27, 95% : 1.08-1.50, = 0.004), complete remission (CR) ( = 1.61, 95% : 1.05-2.47, = 0.03) and C3 levels ( = 0.27, 95% : 0.14-0.39, < 0.000 1), C4 levels ( = 0.12, 95% : 0.07-0.17, < 0.000 01). No significant differences were seen in TR, CR, proteinuria, serum creatinine, C3 and C4 (TR: = 1.00, 95% : 0.87-1.16, = 0.95; CR: = 1.10, 95% : 0.78-1.56, = 0.58; proteinuria levels: = -0.06, 95% : -0.13 to 0.01, = 0.10; serum creatinine levels: = -0.01, 95%: -7.36 to 7.35, = 1.00; C3 levels: = 0.01, 95%: -0.06 to 0.07, = 0.84; C4 levels: = -0.01, 95%: -0.03 to 0.01, = 0.49) between azathioprine (AZA) / leflomit (LEF) + GC and TG tablet + GC. Adverse events (hepatic dysfunction, nausea, vomitting) showed no statistical differences between the TG tablet + GC group and the GC group. There were more new onset of irregular menstruation in the TG tablet + GC group than those in the AZA + GC ( = 3.57, 95% : 1.40-9.11, = 0.008) /LEF+ GC ( = 6.69, 95% : 2.42-18.46, = 0.000 2) group, but leucopenia lower than those in AZA + GC group ( = 0.38, 95% : 0.17-0.85, = 0.02) and alopecia ( = 0.14, 95% : 0.03-0.77, = 0.02) and rash ( = 0.09, 95% : 0.01-0.69, = 0.02) lower than those in LEF + GC group. CONCLUSIONS: This review indicates that TG tablet maybe effective in LN treatment. Nevertheless, adverse events cannot be ignored. Large sample, multi-center, high-quality clinical studies are needed to verify the exact effects and safety of TG tablet in treatment of LN.

[An in vitro study on metabolic interaction between main active components of Salviae Miltiorrhizae Radix et Rhizoma and tacrolimus].

The purpose of this study was to investigate the inhibitory effects of the main active components of Salviae Miltiorrhizae Radix et Rhizoma on the metabolism of tacrolimus mediated by CYP3 A4/5 enzyme, so as to predict the potential drug-drug interaction(DDI) in clinical use. First, the reversible inhibitory activities of five active components of Salviae Miltiorrhizae Radix et Rhizoma(tanshinone Ⅰ, tanshinone Ⅱ_A, cryptotanshinone, salvianolic acid B, dihydrotanshinone Ⅰ) on the metabolism of tacrolimus was investigated by using human liver microsomes(HLM) and recombinant human CYP3 A4/5 enzyme in vitro, then the dose-dependent inhibition of CYP3 A4/5 activity was calculated in HLM. Finally, the time-dependent inhibition(TDI) activities of five active components were studied in HLM through the robust single point inhibition test. In addition, a simple and rapid liquid chromatography tandem mass spectrometry method(HPLC-MS/MS) for the determination of tacrolimus was established in this study. The results showed that dihydrotanshinone Ⅰ had a strong inhibitory effect on the metabolism of tacrolimus in both HLM and rCYP3 A4/5 enzyme systems, and the inhibitory potential IC_(50) in HLM was 6.0 µmol·L~(-1), while the other four active components of Salviae Miltiorrhizae Radix et Rhizoma exhibited relatively weak inhibition on CYP3 A4/5 activity with inhibition rate less than 30% at 10 µmol·L~(-1). Furthermore, the TDI activity of five active components of Salviae Miltiorrhizae Radix et Rhizoma at 50 µmol·L~(-1) was 5.5%-15.9%. The above results suggested that clinical DDI between tacrolimus and Salviae Miltiorrhizae Radix et Rhizoma may occur when the active components of Salviae Miltiorrhizae Radix et Rhizoma achieved a relative high concentration in human. In conclusion, this study provided a data reference for the research on drug interaction of tacrolimus and Salviae Miltiorrhizae Radix et Rhizoma as well as rational drug use in clinical practice.