[Research progress on chemical constituents and pharmacological activities of small molecule compounds in scorpions].

Scorpions, a group of oldest animals with wide distribution in the world, have a long history of medicinal use. Scorpio, the dried body of Buthus martensii, is a rare animal medicine mainly used for the treatment of liver diseases, spasm, and convulsions in children in China. The venom has been considered as the active substance of scorpions. However, little is known about the small molecules in the venom of scorpions. According to the articles published in recent years, scorpions contain amino acids, fatty acids, steroids, and alkaloids, which endow scorpions with antimicrobial, anticoagulant, metabolism-regulating, and antitumor activities. This paper summarizes the small molecule chemical components and pharmacological activities of scorpions, with a view to providing valuable information for the discovery of new active molecules and the clinical use of scorpions.

Acute and sub-chronic toxicity of tetrandrine in intravenously exposed female BALB/c mice.

OBJECTIVE: To evaluate the acute and sub-chronic toxicity of intravenously administered tetrandrine (TET) in female BALB/c mice. METHODS: The median lethal dose (LD50) of intravenously administered TET was calculated in mice using Dixon's up-and-down method. In the acute toxicity study, mice were intravenously administered with TET at a single dose of 20, 100, 180, 260 and 340 mg/kg, respectively and were evaluated at 14 days after administration. In the sub-acute toxicity study, mice were intravenously administered various doses of TET (30, 90 and 150 mg/kg) each day for 14 consecutive days. Clinical symptoms, mortality, body weight, serum biochemistry, organ weight and histopathology were examined at the end of the experiment, as well as after a 1-week recovery period. RESULT: LD50 was found to be 444.67±35.76 mg/kg. In the acute toxicity study, no statistically signifificant differences in body weight, blood biochemistry, or organ histology were observed between the administration and control groups when mice were intravenously administered with single dose at 20, 100, 180, 260 and 340 mg/kg of TET (P >0.05). In the sub-acute toxicity study, no signifificant changes in body weight, biochemistry and organ histology were observed with up to 90 mg/kg of TET compared with the control group (P >0.05), however, in the 150 mg/kg administered group, TET induced transient toxicity to liver, lungs and kidneys, but withdrawal of TET can lead to reversal of the pathological conditions. CONCLUSIONS: The overall fifindings of this study indicate that TET is relatively non-toxic from a single dose of 20, 100, 180, 260 or 340 mg/kg, and that up to 90 mg/kg daily for 14 consecutive days can be considered a safe application dose.

An in vitro and in vivo study on the synergistic effect and mechanism of itraconazole or voriconazole alone and in combination with tetrandrine against Aspergillus fumigatus.

In this study, we investigated the in vitro antifungal effects of itraconazole/voriconazole (ITR/VRC) alone and in combination with tetrandrine (TET) against 23 clinical isolates of A. fumigatus using a chequerboard microdilution method. The dynamic antifungal effects of TET with ITR/VRC against A. fumigatus were assessed in vivo using time-kill curves following systemic infection of mice with A. fumigatus. After treatment, efflux pump activity was determined by the efflux of rhodamine 6G (R6G). When ITR was combined with TET, ITR MICs were reduced from 0.125-32 to 0.0625-2 µg ml(-1), and TET MICs were reduced from 256-512 to 8-64 µg ml(-1). When VRC was combined with TET, VRC MICs were reduced from 0.125-2 to 0.03125-0.5 µg ml(-1), and TET MICs were reduced from 256-512 to 8-256 µg ml(-1). Time-kill curves revealed that A. fumigatus viability was reduced after treatment with ITR/VRC combined with TET versus ITR/VRC alone. ITR/VRC combined with TET significantly prolonged mouse survival and reduced kidney and brain tissue burdens versus ITR/VRC alone (P < 0.05). Moreover, TET inhibited R6G efflux of A. fumigatus. Thus, in vitro and in vivo, TET acted synergistically with ITR/VRC against A. fumigatus, and the synergistic mechanism was related to inhibition of the drug efflux pump.