Evidence for Shikonin acting as an active inhibitor of human carboxylesterases 2: Implications for herb-drug combination
| Autor: | Jingjing Wu, Guang-Bo Ge, Bin Guo, Jia-Nan Li, Yun-Feng Cao, Rong-Rong He |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Drug media_common.quotation_subject Endogeny Pharmacology Carboxylesterase 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Humans Binding site media_common Plants Medicinal biology Chemistry Area under the curve Prodrug Lithospermum erythrorhizon biology.organism_classification Naphthoquinone Drug Combinations 030104 developmental biology 030220 oncology & carcinogenesis Microsome Naphthoquinones |
| Zdroj: | Phytotherapy Research. 32:1311-1319 |
| ISSN: | 0951-418X |
| Popis: | Shikonin, a natural naphthoquinone compound derived from the herb Lithospermum erythrorhizon, is widely used for its various pharmacological activities. However, its potential interactions with other medications by inhibiting human carboxylesterases 2 (hCE2) remain unknown. In this study, the inhibitory effects of shikonin on the activity of hCE2 in human liver microsomes are investigated by using fluorescein diacetate (FD), N-(2-butyl-1,3-dioxo-2,3-dihydro-1H-phenalen-6-yl)-2-chloroacetamide (NCEN), and CPT-11 as substrates of hCE2. The results demonstrate that shikonin significantly inhibits the activity of hCE2 when FD and NCEN are used as substrates, whereas the half inhibition concentration value of shikonin increased by 5-30 times when CPT-11 was used as the substrate. The inhibition types of shikonin against hCE2 activity reflected by 3 substrates were all best fit to noncompetitive manners. In addition, shikonin was found to distinctly suppress endogenous hCE2 activity, characterized with attenuated fluorescence. Furthermore, for drugs metabolized by hCE2 with the similar binding sites with FD or NCEN, the estimated magnitudes of area under the curve variation were approximately 9-357% in the presence of shikonin. Also, the area under the curve of CPT-11 could be increased by 1-14% following administration of shikonin. These findings have clear clinical implications for the combination of shikonin and hCE2-metabolizing prodrugs. |
| Databáze: | OpenAIRE |
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