巴豆叶提取物通过诱导 caspase 3/7 激活，并具有额外的抗炎和抗氧化活性，从而抑制癌细胞生长。
Croton gratissimus leaf extracts inhibit cancer cell growth by inducing caspase 3/7 activation with additional anti-inflammatory and antioxidant activities.
机构信息
Phytomedicine Programme, Department of Paraclinical Sciences, Faculty of Veterinary Science, University of Pretoria, Private Bag X04, Onderstepoort, Pretoria, 0110, South Africa.
Department of Biochemistry, Faculty of Science, University of Yaoundé I, P.O. Box 812, Yaoundé, Cameroon.
出版信息
BMC Complement Altern Med. 2018 Nov 14;18(1):305. doi: 10.1186/s12906-018-2372-9.
BACKGROUND
Croton species (Euphorbiaceae) are distributed in different parts of the world, and are used in traditional medicine to treat various ailments including cancer, inflammation, parasitic infections and oxidative stress related diseases. The present study aimed to evaluate the antioxidant, anti-inflammatory and cytotoxic properties of different extracts from three Croton species.
METHODS
Acetone, ethanol and water leaf extracts from C. gratissimus, C. pseudopulchellus, and C. sylvaticus were tested for their free radical scavenging activity. Anti-inflammatory activity was determined via the nitric oxide (NO) inhibitory assay on lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages, and the 15-lipoxygenase inhibitory assay using the ferrous oxidation-xylenol orange assay. The cytotoxicity of the extracts was determined on four cancerous cell lines (A549, Caco-2, HeLa, MCF-7), and a non-cancerous African green monkey (Vero) kidney cells using the tetrazolium-based colorimetric (MTT) assay. The potential mechanism of action of the active extracts was explored by quantifying the caspase-3/- 7 activity with the Caspase-Glo® 3/7 assay kit (Promega).
RESULTS
The acetone and ethanol leaf extracts of C. pseudopulchellus and C. sylvaticus were highly cytotoxic to the non-cancerous cells with LC varying between 7.86 and 48.19 μg/mL. In contrast, the acetone and ethanol extracts of C. gratissimus were less cytotoxic to non-cancerous cells and more selective with LC varying between 152.30 and 462.88 μg/mL, and selectivity index (SI) ranging between 1.56 and 11.64. Regarding the anti-inflammatory activity, the acetone leaf extract of C. pseudopulchellus had the highest NO inhibitory potency with an IC of 34.64 μg/mL, while the ethanol leaf extract of the same plant was very active against 15-lipoxygenase with an IC of 0.57 μg/mL. A linear correlation (r<0.5) was found between phytochemical contents, antioxidant, anti-inflammatory and cytotoxic activities of active extracts. These extracts induced differentially the activation of caspases - 3 and - 7 enzymes in all the four cancerous cells with the highest induction (1.83-fold change) obtained on HeLa cells with the acetone leaf extract of C. gratissimus.
CONCLUSION
Based on their selective toxicity, good antioxidant and anti-inflammatory activities, the acetone and ethanol leaf extracts of C. gratissimus represent promising alternative sources of compounds against cancer and other oxidative stress related diseases.
背景
巴豆属（大戟科）分布于世界各地，用于传统医学治疗各种疾病，包括癌症、炎症、寄生虫感染和氧化应激相关疾病。本研究旨在评估三种巴豆属植物的不同提取物的抗氧化、抗炎和细胞毒性特性。
方法
用丙酮、乙醇和水提取大戟、假巴豆和巴豆的叶子，测试其自由基清除活性。通过脂多糖（LPS）刺激的 RAW 264.7 巨噬细胞中的一氧化氮（NO）抑制测定和亚铁氧化-二甲酚橙测定法测定 15-脂氧合酶抑制活性，来测定抗炎活性。用四唑盐比色（MTT）测定法在四种癌细胞系（A549、Caco-2、HeLa、MCF-7）和非癌细胞系（非洲绿猴肾细胞系 Vero）上测定提取物的细胞毒性。用 Caspase-Glo® 3/7 测定试剂盒（Promega）定量测定半胱天冬氨酸酶-3/-7 活性，以探索活性提取物的潜在作用机制。
结果
大戟和巴豆的丙酮和乙醇叶提取物对非癌细胞高度细胞毒性，LC 范围为 7.86-48.19μg/mL。相比之下，大戟的丙酮和乙醇提取物对非癌细胞的细胞毒性较小，选择性较强，LC 范围为 152.30-462.88μg/mL，选择性指数（SI）范围为 1.56-11.64。关于抗炎活性，假巴豆的丙酮叶提取物具有最高的 NO 抑制效力，IC 为 34.64μg/mL，而同一植物的乙醇叶提取物对 15-脂氧合酶非常活跃，IC 为 0.57μg/mL。在活性提取物的植物化学物质含量、抗氧化、抗炎和细胞毒性活性之间发现了线性相关性（r<0.5）。这些提取物在所有四种癌细胞中不同程度地诱导了半胱天冬氨酸酶-3 和-7 酶的激活，用大戟的丙酮叶提取物对 HeLa 细胞的诱导最高（1.83 倍变化）。
结论
基于其选择性毒性、良好的抗氧化和抗炎活性，大戟和巴豆的丙酮和乙醇叶提取物是对抗癌症和其他氧化应激相关疾病的有前途的化合物替代来源。
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