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.

A mycophenolic acid derivative from the fungus Penicillium sp. SCSIO sof101.

Mycophenolic acid (MPA) is a group of metabolite derived from several species of Penicillium, which shows potent bioactivity. In this study, a new derivative of MPA compound named penicacid D (1), was isolated from the marine derived fungus Penicillium sp. SCSIO sof101, along with seven known compounds (2-8). Their structures were elucidated based on the HR-ESI-MS and NMR data. Moreover, the 1H and 13C NMR data of compound 2 and the 13C NMR data of compound 3 are reported. Compounds 1, 4 and 6 exhibited weak activities against Escherichia coli (clinical isolation number 100385570) and Acinetobacter baumannii (clinical isolation number 100069).

[Effects of methyl cantharidimide tablets on urinary protein and enzymes in Beagle dogs].

OBJECTIVE: To investigate the nephrotoxic effects of methyl cantharidimide tablets on urinary protein and enzymes in Beagle dogs. METHOD: Beagle dogs were randomly divided into negative control group(blank tablet), methyl cantharidimide tablets group (6.11,12.21, 24.42 mg x kg(-1)), continuously 30 days of oral adminiStration, once a day. The drug and control group were collected and determined fresh urine in 1, 2, 3 and 4 weeks of the administration; Serum urea nitrogen (BUN), creatinine (Crea), total protein (TP) and albumin (ALB) as well as sodium, potassium, chloride electrolyte were determined on 15 and 30 days of the administration; Urine albumin (mAlb), kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin( NGAL), N-acetyl-beta-D-glucosaminidase (NAG), clusterin, beta2-microglobulin (beta2-MG), alpha1-microglobulin (alpha1-MG), alanine aminopeptidase( AAP) and im- munoglobulins IgG were tested on 15 and 30 days of the administration. RESULT: Compared with the control group, urine protein and white blood cells was significantly increased in each dose group. On 15 days of the administration, mAlb were higher in each dose group, KIM-1, NGAL, clusterin, NAG and AAP were significantly higher in high-dose group, while the middle and low dose group had no significant difference, as well as blood SCr and BUN no obvious abnormalities. On 30 days, mAlb, KIM-1, clusterin, NAG, AAP were increased in each dose group, appearing dose-effect relationship, beta2-MG and NGAL levels were significantly increased in high-dose group. Contents above indicators were increased with significant dose and time relationship, and serum BUN, Scr were correlated, suggesting that urine mAlb, KIM-1, clusterin, NAG and AAP indicators that can sensitively respond the changes of proteins and enzymes in urine. CONCLUSION: Methyl cantharidimide tablets has a renal toxicity, urine mAlb, KIM-1, clusterin, NAG and AAP can be used as the early nephrotoxic biomarkers of methyl cantharidimide tablets.