Subchronic toxicity evaluation of Huobahuagen extract and plasma metabolic profiling analysis combined with conventional pathology methods.

Huobahua, namely, Tripterygium hypoglaucum (Levl.) Hutch, known as a traditional Chinese herbal medicine, especially its underground parts, has been widely developed into several Tripterygium agents for the treatment of rheumatoid arthritis and other autoimmune diseases. It has sparked wide public concern about its safety, such as multi-organ toxicity. However, the toxic characteristics and damage mechanism of Huobahuagen extract (HBHGE) remain unclear. In the present study, subchronic oral toxicity study of HBHGE (10.0 g crude drug/kg/day for 12 weeks) was performed in male rats. Hematological, serum biochemical, and histopathological parameters, urinalysis, and plasma metabolic profiling were assessed. The single-dose subchronic toxicity results related to HBHGE exhibited obvious toxicity to the testis and epididymis of male rats. Furthermore, plasma metabolomics analysis suggested that a series of metabolic disorders were induced by oral administration of HBHGE, mainly focusing on amino acid (glutamate, phenylalanine, and tryptophan) metabolisms, pyrimidine metabolism, glutathione metabolism, and steroid hormone biosynthesis. Moreover, it appeared that serum testosterone in male rats treated with HBHGE for 12 weeks, decreased significantly, and was susceptible to the toxic effects of HBHGE. Taken together, conventional pathology and plasma metabolomics for preliminarily exploring subchronic toxicity and underlying mechanism can provide useful information about the reduction of toxic risks from HBHGE and new insights into the development of detoxification preparations.

[Effect of traditional Chinese medicine injections on type I allergy].

OBJECTIVE: To investigate allergic reactions of traditional Chinese medicine (TCM) injections, and to determine the contents of serum IgE and histamine in sensitized animal. The correlation between the preceding contents in serum and allergic reactions may be found, thus offering experimental evidences for advancing the accuracy of anticipation by type I allergy. METHOD: We carried out passive cutaneous anaphylaxis (PCA) tests,active systemic anaphylaxis (ASA) tests and anaphylactoid reactions using three TCM injections, and determined the contents of serum OVA-sIgE, total serum IgE and histamine in sensitized animals by ELISA method. RESULT: The results of PCA test were negative, and there was no significant difference for total serum IgE level between experimental group and normal saline group. In the study of adjuvant effect in TCM injections + OVA (at the dose level that doesn't cause allergic reactions), the PCA results of SHL and YXC were positive and there was a increase in content of serum OVA-sIgE, while the PCA result of QKL was negative with a unobvious increase in the content of serum OVA-sIgE. The content of total serum IgE wasn't remarkably increased in each group and the results of ASA test were all positive. Three injections all caused anaphylactoid symptoms in guinea pigs in different doses or injection speed and the response intensity was found to be dosage and injection speed dependant. Furthermore, there was no significant difference for the content of total serum IgE in each group, whereas serum histamine concentration in every experimental group was markedly higher than normal saline group. CONCLUSION: SHL and YXC increase the sensitivity of guinea pigs on OVA, and three TCM injections can cause allergic reactions in guinea pig. Allergic reactions of three TCM injections are correlated with specific IgE antibodies and histamine contents.