Hamza Rasha A, Mostafa Islam, Mohamed Yasmin S, Dora Gamal A, Ateya Abdel-Monem, Abdelaal Mahmoud, Fantoukh Omer I, Alqahtani Abdulaziz, Attia Rasha A
Department of Pharmacognosy, Faculty of Pharmacy, Zagazig University, 44519 Zagazig, Egypt.
Department of Pharmacology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Saudi Pharm J. 2023 Jan;31(1):125-134. doi: 10.1016/j.jsps.2022.11.011. Epub 2022 Nov 21.
Hepatocellular carcinoma (HCC) is one of the leading causes of mortality worldwide; therefore, searching for an effective treatment for this illness is of great importance. In the present work, cytotoxic activity of the ethanol extract of the aerial parts of L. against human liver carcinoma cells (Hep G2) was tested. Additionally the antitumor activity of the extract was confirmed using chemically induced rat liver carcinogenesis with diethylnitrosamine (DEN). Moreover, bioguided fractionation and column chromatographic separation of the active compounds were carried out. The extract of showed a promising cytotoxic activity according to the protocols of the National Cancer Institute. Bioguided chromatographic separation of the ethanol extract of led to the isolation of seven secondary metabolites including two sesquiterpene lactones as the principal active components of the methylene chloride soluble fraction, grosheimin (IC = 7.49 µg/mL) and cynaropicrin (IC = 13.9 µg/mL). The compounds were characterized by different spectroscopic techniques such as EI-MS, IR and NMR. Additionally, analysis of the two active compounds revealed their ability to bind with caspase-3 via hydrogen bonds interactions to initiate apoptosis of cancer cells. The results shed the light on the significance of as a potential source of antitumor agents.
肝细胞癌（HCC）是全球主要的致死原因之一；因此，寻找针对这种疾病的有效治疗方法至关重要。在本研究中，测试了L.地上部分乙醇提取物对人肝癌细胞（Hep G2）的细胞毒活性。此外，使用二乙基亚硝胺（DEN）化学诱导大鼠肝癌发生模型证实了该提取物的抗肿瘤活性。此外，还对活性化合物进行了生物导向分级分离和柱色谱分离。根据美国国立癌症研究所的方案，该提取物显示出有前景的细胞毒活性。对L.乙醇提取物进行生物导向色谱分离，得到了七种次生代谢产物，其中包括两种倍半萜内酯，它们是二氯甲烷可溶部分的主要活性成分，即格罗舍明（IC = 7.49 µg/mL）和菜蓟苦素（IC = 13.9 µg/mL）。这些化合物通过诸如电子轰击质谱（EI-MS）、红外光谱（IR）和核磁共振（NMR）等不同的光谱技术进行表征。此外，对这两种活性化合物的分析揭示了它们通过氢键相互作用与半胱天冬酶-3结合以引发癌细胞凋亡的能力。这些结果揭示了L.作为潜在抗肿瘤药物来源的重要性。
