Potential accumulation of protopanaxadiol-type ginsenosides in six-months toxicokinetic study of SHENMAI injection in dogs.

SHENMAI injection (SMI), derived from famous Shen Mai San, is a herbal injection widely used in China. Ginsenosides are the major components of SMI. To monitor the exposure level of SMI during long-term treatment, a 6-month toxicokinetic experiment was performed. Twenty-four beagle dogs were dived into four groups (n = 6 in each group): a control group (0.9% NaCl solution) and three SMI groups (2, 6 or 3 mg/kg). The dogs were i.v. infused with vehicle or SMI daily for 180 d. Blood samples for analysis were collected at specific time points as follows: pre-dose (0 h); at 10, 30, and 60 min during infusion; and at 10, 30, 60, 90, 120, 240, and 300 min post-administration. Concentrations of ginsenosides Rb1, Rb2, Rc, Rd, Re, Rf, and Rg1 in the plasma were determined simultaneously by liquid chromatography-tandem mass spectrometry. Non-compartmental parameters were further calculated and analyzed. Significant differences were found between the kinetic behavior of 20(S)-protopanaxadiol-type (PPD-type) and 20(S)-protopanaxatriol-type (PPT-type) ginsenosides. Increasing in the exposure level of PPD-type ginsenosides was observed in dogs during the experiment. Therefore, PPD-type ginsenosides are closely related to the immunity modulation effect of SMI. Increased PPD-type ginsenoside exposure level may present potential toxicity and induce drug-drug interaction risks during SMI administration. As such, PPD-type ginsenoside accumulation must be carefully monitored in future SMI research.

Protective effect of Lycium barbarum on doxorubicin-induced cardiotoxicity.

The objective of this work was to explore the hypothesis that Lycium barbarum (LB) may be protective against doxorubicin (DOX)-induced cardiotoxicity through antioxidant-mediated mechanisms. Male SD rats were treated with distilled water or a water extract of LB (25 mg/kg, p.o.) daily and saline or DOX (5 mg/kg, i.v.) weekly for 3 weeks. Mortality, general condition and body weight were observed during the experiment. DOX-induced cardiotoxicity was assessed by electrocardiograph, heart antioxidant activity, serum levels of creatine kinase (CK) and aspartate aminotransferase (AST) and histopathological change. The DOX group showed higher mortality (38%) and worse physical characterization. Moreover, DOX caused myocardial injury manifested by arrhythmias and conduction abnormalities in ECG (increased QT and ST intervals and ST elevation), a decrease of heart antioxidant activity, an increase of serum CK and AST, as well as myocardial lesions. Pretreatment with LB significantly prevented the loss of myofibrils and improved the heart function of the DOX-treated rats as evidenced from lower mortality (13%), normalization of antioxidative activity and serum AST and CK, as well as improving arrhythmias and conduction abnormalities. These results suggested that LB elicited a typical cardioprotective effect on DOX-related oxidative stress. Furthermore, in vitro cytotoxic study showed the antitumor activity of DOX was not compromised by LB. It is possible that LB could be used as a useful adjunct in combination with DOX chemotherapy.