2. Academic Validation
  3. Rapid identification of urokinase plasminogen activator inhibitors from Traditional Chinese Medicines based on ultrafiltration, LC-MS and in silico docking

Rapid identification of urokinase plasminogen activator inhibitors from Traditional Chinese Medicines based on ultrafiltration, LC-MS and in silico docking

  • J Pharm Biomed Anal. 2019 Feb 5;164:241-248. doi: 10.1016/j.jpba.2018.10.036.
Li Li 1,  Jing Kong 1,  Chun-Hua Yao 1,  Xiu-Feng Liu 2,  Ji-Hua Liu 3
Affiliations

Affiliations

  • 1 Jiangsu Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, 211198, PR China.
  • 2 Jiangsu Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, 211198, PR China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu, 211198, PR China. Electronic address: xf.liu@cpu.edu.cn.
  • 3 Jiangsu Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, 211198, PR China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu, 211198, PR China. Electronic address: liujihua@cpu.edu.cn.
PMID: 30396051 DOI: 10.1016/j.jpba.2018.10.036
Abstract

The urokinase plasminogen activator (uPA) is regarded as the crucial trigger for plasmin generation, which is involved in several diseases especially for neoplasm metastasis. In this study, an efficient approach integrating ultrafiltration, LC/MS, bioassay and in silico docking, was proposed for rapidly detecting uPA ligands from Traditional Chinese Medicines (TCMs). Forty-two TCMs were initially assessed, and as illustrative case studies, Galla Chinensis and Sanguisorbae Radix, which appeared significant inhibitory activities on uPA, were chosen to develpe and verify the strategy. A total of seven uPA ligands were successfully detected and identified. Two of them, pentagalloylglucose and 28-O-β-d-glucopyranosyl pomolic acid, were demonstrated to be potential inhibitors, with IC50 at 1.639 μM and 37.82 μM repectively. Furthermore, a combinatorial compound library screening combined with in silico docking assay, was revealed that ursolic acid (IC50 = 2.623 μM) was also speculated to be a potent parent structure for inhibition of uPA. This approach offers a multidimensional perspective to discover uPA-binding leading compounds from TCMs or other complex mixtures, which would provide an efficient route for drug discovery.

Keywords

Inhibitor; Natural product; UF–LC–MS; Urokinase plasminogen activation.

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