Subchronic toxicity of Acorus gramineus rhizoma in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Acorus gramineus rhizoma (AGR) is the dry rhizome of Acorus gramineus Solander from the family Araceae that has been used as sedative, analgesic, diuretic, digestive and antifungal agent. AIM OF THE STUDY: To evaluate the no-observed-adverse-effect level (NOAEL) and the toxicity of AGR, following repeated oral administration to rats for 13 weeks. MATERIALS AND METHODS: AGR was administered by oral gavage to groups of rats (10 per group, each sex) at doses of 0 (control), 25, 74, 222, 667, or 2,000mg/kg/day, 5 times per week for 13 weeks. Mortality, clinical signs, body weights, food consumption, hematology, serum chemistry, urinalysis, vaginal cytology, sperm motility, sperm morphology, organ weights, gross and histopathological findings were compared between control and AGR groups. RESULTS: No mortality or remarkable clinical signs were observed during this 13-week study. No adverse effects on body weight, food consumption, urinalysis, hematology, serum chemistry, organ weights, gross lesion, histopathology, vaginal cytology, sperm motility or deformity were observed in any of the male or female rats treated with AGR. CONCLUSIONS: On the basis of these results, the NOAEL of AGR is determined to be 2,000mg/kg/day for male and female rats.

[Pure red cell aplasia and hypogammaglobulinemia after administration of Dioscorea rhizome and Poria cocos].

A 56-year-old woman was referred to our department for detailed examination of anemia. She was diagnosed with pure red cell aplasia (PRCA) associated with severe reticulocytopenia based on blood testing and severe erythroblastopenia based on bone marrow aspiration. Blood tests revealed severe hypogammaglobulinemia, but monoclonal protein was not detected in either serum or urine by immunoelectrophoresis. Plasma cells were not increased in bone marrow aspirates or the biopsy specimen. Neither osteolytic lesions nor plasmacytoma was detected by computed tomography. We thus ruled out multiple myeloma. She had been treated with various Chinese herbal medicines prescribed at the referring hospital. We suspected PRCA induced by one of the Chinese herbal medicines and completely discontinued all of these herbal preparations. Hematologic testing revealed that the reticulocyte count and hemoglobin concentration began to recover on day 7 and the hemoglobin concentration and IgG levels had reached reference ranges on day 73 after discontinuation of the Chinese herbal medicines. We suspected Sanyaku (Dioscorea rhizome) or Bukuryou (Poria cocos) to have induced PRCA and hypogammaglobulinemia in this patient. To the best of our knowledge, this is the first report of PRCA and hypogammaglobulinemia induced by a Chinese herbal medicine. Clinicians must consider the possibility of drug-induced PRCA and hypogammaglobulinemia in patients taking Chinese herbal preparations.

Safety evaluation of main alkaloids from Rhizoma Coptidis.

ETHNOPHARMACOLOGICAL RELEVANCE: Rhizoma Coptidis (RC), a widely used traditional Chinese medicine, has been used for the treatment of heat-clearing and detoxifying, but there is very little information on its safety. AIM OF THE STUDY: To provide information on the safety of RC, we evaluated the toxicity of the crude RC and RC alkaloids (berberine, coptisine, palmatine and epiberberine) including cytotoxicity, acute toxicity in mice and sub-chronic toxicity in rats. MATERIALS AND METHODS: The cytotoxicity of RC alkaloids was tested in HepG2 and 3T3-L1 cells by the MTT assay. The acute toxicity of RC alkaloids was tested in mice and the mortality was calculated at the end of experiment. For sub-chronic toxicity study, the rats were treated with the RC alkaloids at a dose of 156 mg/kg/day and RC at a dose of 521 mg/kg/day for 90 days. Mortality, clinical signs, body weight changes, organ weights, urinalysis and hematological parameters, gross necropsy and histopathology were monitored during the study period. RESULTS: The cell assay indicates that the IC(50) values of berberine, coptisine, palmatine and epiberberine in HepG2 cells were 48.17, 64.81, 112.80 and 120.58 µg/mL, which in 3T3-L1 cells were 41.76, 56.48, 84.32 and 104.18 µg/mL, respectively. In the acute toxicity assay, the LD(50) values of four alkaloids were 713.57, 852.12, 1533.68 and 1360 mg/kg, respectively. However, in the sub-chronic toxicity study, no mortality and morbidity were observed which could be related to RC alkaloids and RC treatment. Besides, there was no abnormality in clinical signs, body weights, organ weights, urinalysis, hematological parameters, gross necropsy and histopathology in any of the animals after the oral administration of RC alkaloids and RC. CONCLUSIONS: Taking these results together, we came to the conclusion that the toxicity of berberine is the maximum and palmatine is the minimal in four RC alkaloids. The currently recommended doses of RC alkaloids and RC consumed are relatively safe.

Kava, the anxiolytic herb: back to basics to prevent liver injury?

The use of the anxiolytic herb kava has caused toxic liver injury in Western countries and economic problems in South Pacific Islands due to tthe regulatory ban on kava. This analysis shows poor quality of kava raw material as a cause for its toxicity and suggests preventative measures by going back to the traditional use of kava for the sake of the patients and the South Pacific economy.

A metabonomic analysis of urine from rats treated with rhizoma alismatis using ultra-performance liquid chromatography/mass spectrometry.

A metabonomic approach based on ultra-performance liquid chromatography coupled to mass spectrometry (UPLC/MS) was used to study the nephrotoxicity of rhizoma alismatis (RA) in rats. Potential biomarkers of RA toxicity were identified and the toxicological mechanism is discussed. Urine samples were collected from control and treated rats at various stages and analyzed by UPLC/MS in positive ionization mode. Histopathological analysis was used to evaluate renal function. The differences in the metabolic profiles of the control and treated rats were clearly distinguishable with principal components analysis (PCA) of the chromatographic data, and significant changes in 13 metabolite biomarkers were detected in the urine. This metabonomic method combined with PCA could discriminate the treated rats from the control rats on days 60, 120, and 180 after treatment, before serious organic renal damage was apparent on day 180 with histopathology. This research indicates that UPLC/MS-based metabonomic analysis of urine samples can be used to predict the chronic nephrotoxicity induced by rhizoma alismatis.

A research on the erupted fetal diseases caused by traditional Chinese drugs--discussion from the issue that Chinese goldthread rhizome is prohibited in Singapore.

Chinese Goldthread Rhizome is prohibited in Singapore since it is thought to induce neonatal jaundice. In literatures of traditional Chinese medicine, this drug was never treated as a contraindicant for pregnancy, and there were no records and reports on it inducing neonatal jaundice. The results of the authors's experiments showed that Chinese Goldthread Rhizome and berberine had no induction of neonatal jaundice in pregnant rats and mice and newly born rats, and had no influence either on the activity of glucose-6-phosphate dehydrogenase of mice red blood cells. Fetal toxicity of traditional Chinese drugs including Chinese Goldthread Rhizome should be further studied in order to promote the development of traditional Chinese medicine.