Luo Jiaoyang, Qin Jiaan, Fu Yanwei, Zhang Shanshan, Zhang Xingguo, Yang Meihua
Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
School of Life Sciences and Engineering, Southwest Jiaotong University, Chengdu, China.
Front Pharmacol. 2018 Jun 6;9:601. doi: 10.3389/fphar.2018.00601. eCollection 2018.
() is a traditional Chinese herbal medicine which was used for the treatment of fever, pain, and cancer. A compound 6'-hydroxy justicidin B (HJB) isolated from exhibits promising biological properties. However, the mechanism of action and the behavior of HJB remain to be elucidated. In this study, we investigated the mechanism of action of HJB on human leukemia K562 cells and its pharmacokinetic properties in rats. The results demonstrated that HJB significantly inhibited the proliferation of K562 cells and promoted apoptosis. Besides, HJB resulted in decreased mitochondrial membrane potential deltaPSIm, increased the level of the calcium homeostasis regulator protein TRPC6 and cytosolic calcium. The activity of caspase-8, caspase-9 and the expression of p53 were significantly increased after treatment with HJB. Additionally, HJB has rapid absorption rate and relative long elimination , indicating a longer residence time . The results indicate that HJB inhibited the proliferation of K562 cells and induced apoptosis by affecting the function of mitochondria and calcium homeostasis to activate the p53 signaling pathway. The pharmacokinetic study of HJB suggested it is absorbed well and has moderate metabolism . These results present HJB as a potential novel alternative to standard human leukemia therapies.
（）是一种用于治疗发热、疼痛和癌症的传统中草药。从（该草药）中分离出的化合物6'-羟基异紫堇定B（HJB）具有良好的生物学特性。然而，HJB的作用机制及其（体内）行为仍有待阐明。在本研究中，我们研究了HJB对人白血病K562细胞的作用机制及其在大鼠体内的药代动力学特性。结果表明，HJB显著抑制K562细胞的增殖并促进其凋亡。此外，HJB导致线粒体膜电位ΔΨm降低，钙稳态调节蛋白TRPC6水平和胞质钙增加。用HJB处理后，半胱天冬酶-8、半胱天冬酶-9的活性及p53的表达显著增加。此外，HJB吸收速率快且消除（半衰期）相对较长，表明其停留时间较长。结果表明，HJB通过影响线粒体功能和钙稳态来激活p53信号通路，从而抑制K562细胞的增殖并诱导其凋亡。HJB的药代动力学研究表明其吸收良好且代谢适中。这些结果表明HJB是标准人类白血病治疗方法的一种潜在新型替代药物。
