Study on material basis of cathepsin K targeted inhibitor in Erzhi Wan
10.12206/j.issn.2097-2024.202202008
- VernacularTitle:二至丸中抑制组织蛋白酶K活性的物质基础研究
- Author:
Yiping JIANG
1
;
Yue JIN
2
;
Zhiwei ZHANG
2
;
Tianshuang XIA
1
;
Jiale XU
3
;
Liming XUE
2
Author Information
1. Department of Pharmacognosy, Naval Medical University, Shanghai 200433, China.
2. Institute of Chemical Toxicity, Shanghai Municipal Center for Disease Control and Prevention, Shanghai 200336, China;Shanghai institutes of Preventive Medicine, Shanghai 200336, China.
3. Institute of Chemical Toxicity, Shanghai Municipal Center for Disease Control and Prevention, Shanghai 200336, China.
- Keywords:
Erzhi Wan;
osteoporosis;
cathepsin K;
active fraction;
potential inhibitor
- From:
Journal of Pharmaceutical Practice
2023;41(2):91-96
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the active ingredients and components that inhibiting cathepsin K activity in Erzhi Wan, a classic kidney-tonifying formula. Methods Then-butanol, dichloromethane, ethyl acetate and petroleum ether parts and 30 active components in Erzhi Wan were screened by established high throughput fluorescence methods of inhibit the binding activity of CTSK with Z-FR-MCA substrate, the formation of CTSK and chondroitin sulfate A (CSA) complex activity, and the activity of substrate type I collagen degradation by CTSK. Molecular docking and insoluble collagen substrate binding assays were applied to verify the potential CTSK inhibitors. Results The n-butanol and petroleum ether parts of Erzhi Wan inhibited the formation of CTSK and CSA* complex by more than 90%, the petroleum ether part inhibited the binding of CTSK to substrate Z-FR-MCA by more than 90%, the collagen degradation inhibition rate of CTSK in n-butanol part was more than 95% and that in petroleum ether part was 58.6%. Among the 30 active components, 11 showed that the inhibition rate of CTSK and CSA* complex formation was more than 50%, and 5 components with the inhibition rate of Z-FR-MCA binding activity more than 50%. Finally, there were four components including eclalbasaponin Ⅸ, (-)-epicatechin gallate, nuezhenoside and wedelolactone. The inhibition rate of collagen degradation was more than 50%. Eclipta saponin IX inhibited the binding rate between collagen fibers and CTSK, up to 60%, but all of them failed to dock with CTSK active site. Conclusion There are active components that inhibiting cathepsin K in Erzhi Wan, which mainly exists in the n-butanol ingredients, but the active components is not an active-site inhibitor. It might inhibit the binding of CTSK with oligosaccharides by binding to other sites of CTSK, and then reduce the collagen degradation activity of CTSK.
