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四棱豆(Schumm. & Thonn.)Taub.(豆科)果实提取物的细胞毒性、急性和亚慢性毒性。

Cytotoxicity, acute and sub-chronic toxicities of the fruit extract of Tetrapleura tetraptera (Schumm. & Thonn.) Taub. (Fabaceae).

机构信息

Department of Biochemistry, Faculty of Science, University of Dschang, Dschang, Cameroon.

Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128, Mainz, Germany.

出版信息

BMC Complement Med Ther. 2022 Jul 4;22(1):178. doi: 10.1186/s12906-022-03659-1.

Abstract

BACKGROUND

Tetrapleura tetraptera is a medicinal spice traditionally used to treat cancer, diabetes, and several other ailments. This study analyzed the cytotoxicity of the dichloromethane methanol extract of T. tetraptera fruits (TTF) and its constituents. The toxicity profile of the TTF extract was also evaluated in rats.

METHODS

The Cytotoxicity of this extract was evaluated using the resazurin reduction assay (RRA). Acute and sub-chronic toxicity studies were performed according to the protocol described by the Organisation for Economic Cooperation, and Development (OECD). Hematological, serum, and urine biochemical parameters, as well as histological sections of the liver and kidney, were also evaluated based on standard methods.

RESULTS

The TTF extract, compound 5, and the reference drug doxorubicin were active in all 9 tested cancer cell lines. The recorded IC ranged from 18.32 μM (against B16-F1 murine melanoma cells) to 36.18 μM (against SKMel-505 BRAF wildtype melanoma cells) for TTF, from 10.02 μM (towards MaMel-80a BRAF-V600E homozygous mutant melanoma cells) to 31.73 μM (against SKMel-28 BRAF-V600E homozygous mutant melanoma cells) for compound 5, and from 0.22 μM (against B16-F1 cells) to 9.39 μM (against SKMel-505 cells) for doxorubicin. The study of acute toxicity test showed that the lethal dose (LD) of this extract was greater than 5000 mg/kg body weight. In the sub-chronic toxicity studies, variations were observed in some biochemical parameters, especially at higher doses.

CONCLUSION

TTF and its most active compound (5) are found to be potential cytotoxic agents, meanwhile, TTF was safe when given a single oral dose of 5000 mg/kg. However, caution is necessary in case of prolonged oral administration due to potential alterations of renal function at high doses (> 1000 mg/kg).

摘要

背景

棱果木是一种药用香料,传统上用于治疗癌症、糖尿病和其他几种疾病。本研究分析了棱果木果实的二氯甲烷甲醇提取物(TTF)及其成分的细胞毒性。还评估了 TTF 提取物在大鼠中的毒性概况。

方法

使用 Resazurin 还原测定法(RRA)评估该提取物的细胞毒性。根据经济合作与发展组织(OECD)的协议进行了急性和亚慢性毒性研究。根据标准方法评估了血液学、血清和尿液生化参数以及肝和肾组织学切片。

结果

TTF 提取物、化合物 5 和参考药物多柔比星在所有 9 种测试的癌细胞系中均具有活性。记录的 IC 范围从 TTF 的 18.32 μM(针对 B16-F1 鼠黑色素瘤细胞)到 36.18 μM(针对 SKMel-505 BRAF 野生型黑色素瘤细胞),化合物 5 的 10.02 μM(针对 MaMel-80a BRAF-V600E 纯合突变黑色素瘤细胞)到 31.73 μM(针对 SKMel-28 BRAF-V600E 纯合突变黑色素瘤细胞),多柔比星的 0.22 μM(针对 B16-F1 细胞)到 9.39 μM(针对 SKMel-505 细胞)。急性毒性试验研究表明,该提取物的致死剂量(LD)大于 5000 mg/kg 体重。在亚慢性毒性研究中,观察到一些生化参数发生变化,尤其是在较高剂量时。

结论

TTF 及其最活跃的化合物(5)被发现是潜在的细胞毒性剂,同时,TTF 在口服 5000 mg/kg 时是安全的。然而,由于高剂量(>1000 mg/kg)时肾功能可能发生变化,因此需要谨慎长期口服。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46a9/9252075/011e4b9d2a37/12906_2022_3659_Fig2_HTML.jpg

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