Natural Products Chemistry Lab, Department of Pharmaceutical Sciences and Natural Products, Central University of Punjab, Ghudda, Bathinda 151401, India.
Department of Zoology, Central University of Punjab, Ghudda, Bathinda 151401, India.
Fitoterapia. 2024 Sep;177:106123. doi: 10.1016/j.fitote.2024.106123. Epub 2024 Jul 14.
The Potentilla genus has long been used traditionally as food and a folklore medicine. In the present study, aerial parts of two Potentilla species, Potentilla fulgens and Potentilla atrosanguinea, of western Himalayan origin, were studied for their anti-breast cancer activity. Ethyl acetate (PAA-EA, PFA-EA), methanolic (PAA-ME, PFA-ME) and hydro-methanolic extract (PAA-HM, PFA-HM) of the plants were tested for their antiproliferative activities against MCF-7 and T-47D breast cancer cell lines. The extracts showed good antiproliferative activity against ER-α dominant breast cancer cell line T-47D, having IC values 6.19 ± 0.01 to 33.23 ± 0.04 μg/ml. Eight compounds were isolated, characterized, and quantified from ethyl acetate and methanolic extracts by column chromatography, 1D, 2D-NMR, HRMS and TLC densitometric analysis. Two compounds (4 and 6) have shown better antiproliferative activity than standard bazedoxifene and were further evaluated for their ER-α binding affinity via-fluorescence polarization-based competitive binding assay. The antiestrogenic properties of both compounds were assessed using western blotting. Compounds 4 and 6 were found to have significant affinity for the ER-α and managed to decrease its expression by 38 and 54% respectively. Compounds 4 and 6 also had good stability and reactivity as measured by minimal fluctuations in molecular dynamic simulation analysis, a good dock score in molecular docking, and a respectable HOMO-LUMO energy gap in DFT calculations. Compounds 4 and 6 have shown reliable results and can be used in the development of natural product-based anti-breast cancer agents.
委陵菜属植物长期以来一直被用作食品和民间药物。本研究以产自喜玛拉雅西部的两种委陵菜（翻白委陵菜和二裂委陵菜）的地上部分为研究对象，考察其抗乳腺癌活性。测试了植物的乙酸乙酯（PAA-EA、PFA-EA）、甲醇（PAA-ME、PFA-ME）和水-甲醇提取物（PAA-HM、PFA-HM）对 MCF-7 和 T-47D 乳腺癌细胞系的增殖抑制活性。提取物对 ER-α 优势的乳腺癌细胞系 T-47D 表现出良好的增殖抑制活性，IC 值为 6.19±0.01 至 33.23±0.04μg/ml。通过柱层析、1D、2D-NMR、HRMS 和 TLC 密度分析，从乙酸乙酯和甲醇提取物中分离、鉴定和定量了 8 种化合物。两种化合物（4 和 6）的增殖抑制活性优于标准 bazedoxifene，并用基于荧光偏振的竞争性结合测定法进一步评估了它们对 ER-α 的结合亲和力。通过 Western blot 评估了这两种化合物的抗雌激素特性。发现化合物 4 和 6 对 ER-α 具有显著的亲和力，并分别使其表达降低了 38%和 54%。化合物 4 和 6 在分子动力学模拟分析中分子波动最小、分子对接中的良好对接分数和 DFT 计算中可观的 HOMO-LUMO 能隙方面，也表现出良好的稳定性和反应性。化合物 4 和 6 显示出可靠的结果，可用于开发基于天然产物的抗乳腺癌药物。
