Involvement of Substance P/Neurokinin-1 Receptor in the Analgesic and Anticancer Activities of Minimally Toxic Fraction from the Traditional Chinese Medicine Liu-Shen-Wan in Vitro
Involvement of Substance P/Neurokinin-1 Receptor in the Analgesic and Anticancer Activities of Minimally Toxic Fraction from the Traditional Chinese Medicine Liu-Shen-Wan in Vitro
复制标题
P/神经激肽-1物质受体参与中药六神丸微毒部位的体外镇痛和抗癌活性
DOI：
10.1248/bpb.b13-00794
复制
发表时间：
2014-03-01
影响因子：
2
通讯作者：
Tang, He-Bin
中科院分区：
文献类型：
--
作者：
Li, Xiao-Jun;Jia, Mei-Mei;Tang, He-Bin
六参丸是一种用于治疗局部感染和疼痛的古老制剂，最近被报道具有抗癌活性。LSW的镇痛和抗癌作用机制尚不清楚。在本研究中，我们从超声辅助乙醇提取中获得了LSW上清（LSWS）部分（得率为15.9%），证明其肝毒性比LSW更安全。LSWS（1和10 μ g/mL）对缓激肽诱导的背根神经节（DRG）细胞P物质的快速释放有明显的抑制作用。在0.1 μ g/mL及以上浓度下，LSWS对具有代表性的癌细胞HepG2具有浓度相关的生长抑制作用。在HepG2和缓激肽处理的DRG细胞中，LSWS显著下调神经激肽-1 （NK-1）受体表达。除了对HepG2细胞有NK-1受体依赖性的生长抑制作用（0.1 ~ 100 μ g/mL）外，高浓度的LSWS还能诱导线粒体介导的细胞凋亡（1 ~ 100 μ g/mL）。综上所述，我们最近分离出了一种更安全的LSW组分，该组分保持了其镇痛和抗癌活性，并发现P/NK-1受体系统在一定程度上起了这些作用。我们的发现将有助于开发更有效和更低毒性的LSW制剂。
Liu-Shen-Wan (LSW), an ancient preparation used to treat localized infection with pain, was recently reported to possess anticancer activity. The mechanism responsible for LSW's analgesic and anticancer activity is unclear. In the present study, we obtained a LSW supernatant (LSWS) fraction from ultrasound-assisted ethanol extraction (yield 15.9%) which proved to be safer than LSW in terms of hepatotoxicity. The LSWS (1 and 10 mu g/mL) exhibited a potent inhibitory effect on the bradykinin-evoked rapid release of substance P from dorsal root ganglion (DRG) cells. At concentrations of 0.1 mu g/mL and higher, the LSWS resulted in a concentration-related growth inhibitory effect on HepG2, a representative cancer cell lines. The LSWS significantly down-regulated the neurokinin-1 (NK-1) receptor expression in both HepG2 and bradykinin-treated DRG cells. In addition to the NK-1 receptor-dependent growth inhibition in HepG2 cells (0.1-100 mu g/mL), the LSWS induced mitochondria-mediated apoptosis at a higher concentration (1-100 mu g/mL). In conclusion, we recently isolated a safer LSW fraction which maintained its analgesic and anticancer activity, and found that the substance P/NK-1 receptor system was partly responsible for these effects. Our findings will be useful for developing more effective and less toxic LSW preparations.