Aloe vera gel extract: Safety evaluation for acute and chronic oral administration in Sprague-Dawley rats and anticancer activity in breast and lung cancer cells
Aloe vera gel extract: Safety evaluation for acute and chronic oral administration in Sprague-Dawley rats and anticancer activity in breast and lung cancer cells
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芦荟凝胶提取物：Sprague-Dawley大鼠急性和慢性口服给药的安全性评价以及对乳腺癌和肺癌细胞的抗癌活性
DOI：
10.1016/j.jep.2021.114434
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发表时间：
2021
影响因子：
5.4
通讯作者：
Li Jiejing
中科院分区：
文献类型：
--
作者：
Tong Xueli;Li Min;Li Di;Lao Chunqin;Chen Jingmian;Xu Weijie;Du Junxi;Zhang Meijiao;Yang Xiangcai;Li Jiejing
芦荟（L.）的民族药理学相关性发热管。f.是《中华人民共和国药典（2015版）》中收录的典型中药。传统上，它被用于治疗便秘，其潜在的治疗活性已被广泛评估，包括抗肿瘤、抗炎和免疫调节作用。芦荟食品和治疗的广泛应用引发了安全性问题，并且有多种安全性评估，包括临床和动物的各种毒性和不良反应。目的研究芦荟提取物C （AVBEC）在大鼠体内的安全性，并分析其在细胞系中的抗癌活性。材料与方法采用急性毒性实验和6个月慢性毒性实验，观察并证实AVBEC对SD大鼠的安全性。此外，我们还探讨了AVBEC在癌细胞和非癌细胞中的细胞毒性。我们进一步研究了AVBEC的抗肿瘤活性，同时探讨了AVBEC成分的功能。结果在44.8 g·kg-1和4.48 g·kg-1剂量组的急性毒性研究和6个月的慢性毒性研究中均未见死亡和物质相对毒性。在慢性毒性研究中，AVBEC未引起器官毒性，包括关键器官结构和化学功能，以及外周和中枢免疫系统损伤。此外，我们发现AVBEC通过降低三磷酸腺苷（ATP）浓度和增加活性氧（ROS）的产生，诱导癌细胞凋亡，且凋亡率高于非癌细胞。采用高效液相色谱-串联质谱法（HPLC-MS/MS）对AVBEC中的成分进行了鉴定，并对苹果酸的功能进行了探讨。这表明，在相同的情况下，苹果酸诱导癌细胞和非癌细胞的细胞坏死，而AVBEC没有。结论芦荟凝胶提取物具有调节肿瘤细胞凋亡、调节线粒体代谢的新机制，并通过对大鼠的安全性评价和对肿瘤细胞和非肿瘤细胞的抗癌研究，提示了AVBEC在恶性肿瘤治疗中的应用前景。
Ethnopharmacological relevanceAloe vera (L.) Burm. f. is a typical traditional Chinese medicine (TCM) collected in the Pharmacopoeia of the People's Republic of China (version 2015). It has been traditionally used for the treatment of constipation, and its potential therapeutic activities have been widely evaluated, including anti-tumor, anti-inflammatory and immune regulatory effects. The wide application ofAloe verain food and therapy has raised safety issues and there are multiple safety assessments with a diverse toxicity and adverse effects from clinics and animals.Aim of the studyThis study aimed to investigate the safety ofAloe verabarbadensis extract C (AVBEC) in rats and analyze its anticancer activity in cell lines.Materials and methodsWe administrated AVBEC orally in an acute toxicity study and a 6-month chronic toxicity study to observe and confirm its safety in Sprague-Dawley (SD) rats. Additionally, we explored the cytotoxicity of AVBEC in cancer cells and non-cancer cells. We further investigated the anti-tumor activity of AVBEC, and in the meantime, probed the function of component from AVBEC.ResultsNo deaths or substance-relative toxicity were observed in the acute toxicity study or the 6-month chronic toxicity study with doses of 44.8 g·kg-1and 4.48 g·kg-1, respectively. In the chronic toxicity study, AVBEC did not cause organ toxicity, including crucial organ structure and chemical function, and peripheral and central immune system damage. Additionally, we found that AVBEC could induce cancer cell apoptosis with a relatively higher apoptotic ratio than in non-cancer cells by decreasing adenosine triphosphate (ATP) concentration and enhancing reactive oxygen species (ROS) production. We also identified components in AVBEC using high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) and probed the function of malic acid. This demonstrated that under the same circumstances, malic acid induced cell necrosis in cancer cells and non-cancer cells, while AVBEC did not.ConclusionsThese results reveal a novel mechanism of aloe gel extract in regulating cancer cell apoptosisviamodulating the mitochondrial metabolism and imply a possible application of AVBEC for the treatment of malignant cancer with the safety evaluation from rats and anticancer investigation from cancer cells and non-cancer cells.