PDF(Pubmed)
Abstract：
Two cytotoxic sesquiterpene lactones, 17-epichlorohyssopifolin A (1) and chlorjanerin (2), and a monoterpene lactone, loliolide (3) were isolated from Centaurea pseudosinaica. The cytotoxicity of the total extract and terpenoids 1-3 were evaluated against three human cancer cells (HepG2, PC-3, and HT-29), along with the human normal primary epidermal keratinocytes (HEKa) cells. With IC50 values ranging between 0.6 ± 0.04 and 5.0 ± 0.61 μg/mL against HepG2; 0.2 ± 0.01 and 11.9 ± 1.31 μg/mL against PC-3, and 0.04 ± 0.013 and 8.9 ± 0.97 μg/mL against HT-29, the total extract, and lactones 1-3 demonstrated cytotoxic effects. Compound 1 displayed the strongest impact on all cancer cells and a slightly safe effect on the normal cells HEKa. Compound 1 caused accumulation of HepG2 and HT-29 cells in G1 phase as displayed cell cycle analysis. On the other hand, the cell distributions were increased in the S phase in PC-3 cells. Furthermore, 1 caused apoptosis in PC-3 and HePG2 cells with 91.50%, and 79.72 %, respectively. A higher fraction of necrotic cells was observed in HT-29 cells amounting to 23.60%. These results suggested that the promising cytotoxicity exhibited by 1 is brought by the apoptosis induction in the cancer cells, which were evaluated. As the compounds showed antiproliferative effect against the HT-29 cells, the docking simulation was performed aiming at determining how they would interact with the EGFR enzyme, whose PDB: 4I23 is considered one of the two distinct wild types of EGFR enzymes. The antibacterial activity results revealed that 3 showed the most remarkable antibacterial effects, especially against the examined Gram-positive bacteria. The total extract exhibited potent activity against all examined bacteria. The total extract showed a potent antifungal effect against two Candida and two Aspergillus pathogens. The antioxidant activity revealed the potency of the total extract and 3 as antioxidant candidates. The obtained results refer to the importance of Centaurea pseudosinaica as a source of potent antiproliferative agents and the whole plant as an antipathogenic and antioxidant agent.
摘要：
两种细胞毒性倍半萜内酯，17-表氯酸酯A（1）和氯香精（2），和单萜内酯，loliolide（3）从拟发素中分离。评估总提取物和萜类化合物1-3对三种人类癌细胞（HepG2，PC-3和HT-29）的细胞毒性，以及人类正常的原代表皮角质形成细胞（HEKa）细胞。对HepG2的IC50值在0.6±0.04和5.0±0.61μg/mL之间；对PC-3的IC50值在0.2±0.01和11.9±1.31μg/mL之间，对HT-29的IC50值在0.04±0.013和8.9±0.97μg/mL之间，总提取物，和内酯1-3表现出细胞毒性作用。化合物1对所有癌细胞表现出最强的影响,并且对正常细胞HEKa表现出略微安全的作用。如细胞周期分析所示,化合物1导致HepG2和HT-29细胞在G1期的积累。另一方面,在PC-3细胞中，细胞分布在S期增加。此外，1引起PC-3和HePG2细胞凋亡的比例为91.50%,79.72%,分别。在HT-29细胞中观察到较高比例的坏死细胞达23.60%。这些结果表明，1表现出的有希望的细胞毒性是由癌细胞中的凋亡诱导引起的，进行了评估。由于该化合物对HT-29细胞具有抗增殖作用，对接模拟旨在确定它们如何与EGFR酶相互作用，其PDB:4I23被认为是两种不同的野生型EGFR酶之一。抑菌活性结果表明，3种表现出最显著的抑菌效果，特别是针对检查的革兰氏阳性细菌。总提取物对所有检查的细菌表现出有效的活性。总提取物对两种念珠菌和两种曲霉病原体显示出有效的抗真菌作用。抗氧化活性揭示了总提取物和3作为抗氧化剂候选物的效力。获得的结果指的是矢车菊作为有效的抗增殖剂的来源和整个植物作为抗病原体和抗氧化剂的重要性。
