Hematotoxicity of the Chinese Herbal MedicineTripterygium wilfordiiHook f in CD34-Positive Human Bone Marrow Cells

Abstract

T2, a chloroform/methanol extract of the herb Tripterygium wilfordii Hook f, has been used in China for the treatment of autoimmune and inflammatory diseases for many years. Recent experimental evidence has confirmed that T2 has potent anti-inflammatory and immunosuppressive activity, and a United States Food and Drug Administration-approved clinical trial is currently exploring the efficacy of T2 in the treatment of rheumatoid arthritis. Despite the potential therapeutic benefits of T2, there is ample documentation that T2 is toxic, targeting, among other things, the hematopoietic system, and its use has resulted in cases of leukopenia, thrombocytopenia, and aplastic anemia. This investigation was undertaken to characterize the in vitro effects of T2 on primary human CD34-positive (CD34+) bone marrow cells. Our results demonstrate that T2 has a potent inhibitory effect on the clonogenic response of human bone marrow cells to exogenously added hematopoietic growth factors. The inhibition of colony formation by T2 is not the result of direct cytotoxicity or increased apoptosis and indicates a functional suppression of hematopoiesis. Additional experiments demonstrate that T2 also alters transcriptional regulation in bone marrow cells by inhibiting nuclear factor-kappaB. This transcription factor is found in CD34+ bone marrow cells and has been recently shown to be a requirement for colony formation. These results demonstrate that therapeutic concentrations of T2 exert a significant hematotoxic effect by inhibiting growth factor response in CD34+ bone marrow cells and suggest that inhibition of nuclear factor-kappaB may play a role in the blood dyscrasias encountered with the use of this drug.

Novel cytostatic activity of the trypanocidal drug Benznidazole

“…Interestingly, treatment with T2 has resulted in cases of leukopenia, thrombocytopenia, and aplastic anemia. Similar to BZL treatment, these side effects are often transient and recovery is usually complete upon removal of the drug [24].…”

Traditional Chinese medicine in the treatment of rheumatoid arthritis: a general review

“…Overall, most aspects of RA pathological development were ameliorated due to the multi-targeted function of TWHF or its active ingredients. However, complications co-existed in the clinical application of TWHF which were mainly expressed as skin rashes, cheilosis, diarrhea, amenorrhea and myelosuppression [13,14]. Besides TWHF, many other Chinese herbs such as Stephania tetrandra S Moore, cat's claw, etc.…”

Comparison of toxic reaction of Tripterygium wilfordii multiglycoside in normal and adjuvant arthritic rats

“…GTW showed anti-inflammatory and immunosuppressive activities in human clinical trials for rheumatoid arthritis (RA), systemic lupus erythematosus, nephritis, asthma, and ankylosing spondylitis (Tao et al, 2001). In 2000, the U.S. Food and Drug Administration had approved a clinical trial to evaluate the effects of a chloroform/methanol extract of the herb Tripterygium wilfordii in the treatment of RA (Pyatt et al, 2000). Based on many clinical and experimental researches (GoldbachMansky et al, 2009;Tao et al, 2002), GTW is regarded as a promising drug for the treatment of RA.…”