钩藤碱小鼠急性毒性试验及评价

doi:10.5246/jcps.2021.08.053

摘要/Abstract

摘要：

钩藤碱作为钩藤的主要生物碱成分, 具有抗高血压和神经保护作用, 近年来受到广泛关注。尽管如此, 其毒性的研究仍较少。本研究通过口服给药钩藤碱, 观察其对昆明小鼠的急性毒性反应。昆明小鼠随机分组后分别灌服给药520.00、442.00、375.70、319.34、271.44 mg/kg剂量的钩藤碱, 观察14天, 记录小鼠的一般行为、体重变化、毒性反应和死亡情况, 计算半数致死量(LD₅₀), 并对死亡小鼠进行主要脏器的病理学检查。与对照组相比, 单次给药钩藤碱后小鼠体重未见明显变化, 但是钩藤碱给药后小鼠出现明显的异常症状和死亡率。毒性试验的LD₅₀为308.08 mg/kg, 病理学结果显示钩藤碱高剂量组对小鼠的脑、肝、肺、肾有较明显的毒性作用。本研究表明, 钩藤碱不可长时间或高剂量使用, 本研究可为下一步的临床研究提供有力的依据。

关键词: 钩藤碱, 口服急性毒性, 半数致死量, 小鼠

Abstract:

As the main alkaloid constituent of Uncaria species, rhynchophylline has drawn extensive attention in recent years for its antihypertensive and neuroprotective activities. However, toxicity study of the rhynchophylline is still lacking. In the present study, oral acute toxicity of rhynchophylline was conducted in Kunming mice. The mice were orally treated with 520.00, 442.00, 375.70, 319.34 and 271.44 mg/kg of rhynchophylline for 14 d. The general behavior, body weight changes, toxic reaction, and death were recorded, and histopathological analyses were performed. The acute toxicity was evaluated by the assessment of the median lethal dose (LD₅₀). The acute toxicity study showed that no significant difference was found in the body weight of the mice in the control group and those in the drug group. However, the mice treated with rhynchophylline showed obvious abnormal symptoms and mortality. The median lethal dose (LD₅₀) of orally administered rhynchophylline was 308.08 mg/kg. The histopathological results showed that the mice in the high-dose rhynchophylline group displayed toxic effects in the brain, liver, lung, and kidney. The results of the current study indicated that rhynchophylline could not be taken at a high dose. Collectively, our current findings provided a strong basis for further clinical investigation.

Key words: Rhynchophylline, Acute oral toxicity, Median lethal dose, Mice

Supporting:

胡岚岚, 张惠静, 张乐, 汤建林. 钩藤碱小鼠急性毒性试验及评价[J]. 中国药学(英文版), 2021, 30(8): 657-665.

Lanlan Hu, Huijing Zhang, Le Zhang, Jianlin Tang. Acute oral toxicity test and assessment of rhynchophylline in mice[J]. Journal of Chinese Pharmaceutical Sciences, 2021, 30(8): 657-665.

图/表 4

Table 1. Condition of mice after a single administration of different doses of rhynchophylline.

Figure 1. Mean body weight of treated mice and controls during the study. (There were no significant differences among groups).

Figure 2. Histopathological observation of the heart, spleen, stomach, duodenum, and jejunum from mice treated with 520 mg/kg rhynchophylline group. The observation was made at different ampli?ed levels. A: Heart (HE, × 100); B: Spleen (HE, × 100); C: Stomach (HE, × 40); D: Duodenum; (HE, × 40); E: Jejuna (HE, × 40).

Figure 3. Histopathological observation of liver (A–C), lung (D–F), kidney (G–I), and brain (J-L) in mice. Photomicrographs from representative mice from respective groups: normal control group treated with distilled water (A, D, G, J) at 100 ×, dissolvent control group treated with dimethylsulfoxide (B, E, H, K) at 100 ×, rhynchophylline (520 mg/kg) group (C, F, I, L) at 200 ×.

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