Co-construction Collaborative Innovation Center for Chinese Medicine Resources Industrialization by Shaanxi & Education Ministry, Shaanxi Province Key Laboratory of New Drugs and Chinese Medicine Foundation Research, Shaanxi University of Chinese Medicine, Xianyang, PR China; Jiangsu Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, PR China.
Jiangsu Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, PR China.
Fitoterapia. 2023 Sep;169:105595. doi: 10.1016/j.fitote.2023.105595. Epub 2023 Jun 23.
Ursolic acid (UA) is a pentacyclic triterpenoid widely found in in medicinal plants, edible plants, fruits, and flowers. The great interest in this bioactive compound is related to the positive effects in human health. However, its limited solubility, moderate biological activity and poor bioavailability limit the potential and further applications of UA. Here, we explored the efficacy of MeON-Glycosides of UA in inhibiting tumor cell proliferation. A number of compounds showed significant antitumor activity against tested five cancer cell lines. Among them, compound 2a exhibited the most potent activity against HepG2 cells with IC values of 3.1 ± 0.5 μM. Especially, compound 2a could induce HepG2 cells apoptosis and reduce mitochondrial membrane potential. Western blot analysis showed that compound 2a up-regulated Bax, cleaved caspase-3/9, cleaved PARP levels and down-regulated Bcl-2 level of HepG2 cells. These results indicated that compound 2a could obviously induce the apoptosis of HepG2 cells. At the same time, compound 2a significantly decreased the expression of p-AKT and p-mTOR, which indicated that compound 2a might exert its cytotoxic effect by targeting PI3K/AKT/mTOR signaling pathway. Moreover, the in silico ADME predictions showed that compound 2a has improved water solubility and other properties. Thus, compound 2a may be a promising antitumor candidate, which may be potentially used to prevent or treat cancers.
熊果酸（UA）是一种五环三萜，广泛存在于药用植物、食用植物、水果和花卉中。人们对这种生物活性化合物非常感兴趣，因为它对人类健康有积极影响。然而，其有限的溶解度、中等的生物活性和较差的生物利用度限制了 UA 的潜力和进一步应用。在这里，我们探索了 UA 的 MeON-糖苷在抑制肿瘤细胞增殖方面的功效。许多化合物对测试的五种癌细胞系表现出显著的抗肿瘤活性。其中，化合物 2a 对 HepG2 细胞的活性最强，IC 值为 3.1±0.5 μM。特别是，化合物 2a 可以诱导 HepG2 细胞凋亡并降低线粒体膜电位。Western blot 分析表明，化合物 2a 上调了 Bax、cleaved caspase-3/9、cleaved PARP 水平，并下调了 HepG2 细胞的 Bcl-2 水平。这些结果表明，化合物 2a 可以明显诱导 HepG2 细胞凋亡。同时，化合物 2a 显著降低了 p-AKT 和 p-mTOR 的表达，这表明化合物 2a 可能通过靶向 PI3K/AKT/mTOR 信号通路发挥其细胞毒性作用。此外，基于计算机的 ADME 预测表明，化合物 2a 具有改善的水溶性和其他性质。因此，化合物 2a 可能是一种有前途的抗肿瘤候选药物，可用于预防或治疗癌症。
