Affiliation:
1. School of Life Science and Engineering, Key Laboratory of Drug Screening and Deep Processing for Traditional Chinese and Tibetan Medicine of Gansu Province, Lanzhou University of Technology, Lanzhou 730050, China
2. Drug Evaluation and Certification Center of Gansu Food and Drug Administration, Lanzhou 730060, China
Abstract
Background:Adenosine deaminase (ADA) is an important enzyme in purine metabolism and is known as a potential therapeutic target for the treatment of lymphoproliferative disorders and cancer. Traditional Chinese Herbal Medicine (TCHM) is widely used alone or in combination with chemotherapy to treat cancer, due to its ability to deliver a broad variety of bioactive secondary metabolites as promising sources of novel organic natural agents.Objective:In the present study, 29 varieties of medicinal plants were screened for the presence of ADA inhibitors.Result:Extracts from Reynoutria japonica, Glycyrrhiza uralensis, Lithospermum erythrorhizon, Magnolia officinalis, Gardenia jasminoides, Stephania tetrandra, Commiphora myrrha, Raphanus sativus and Corydalis yanhusuo demonstrated strong ADA inhibition with rates greater than 50%. However, Reynoutria japonica possessed the highest ADA inhibitory activity at 95.26% and so was used in our study for isolating the ADA inhibitor to be further studied. Eight compounds were obtained and their structures were identified. The compound H1 had strong ADA inhibitory activity and was deduced to be emodin by 1H and 13C-NMR spectroscopic analysis with an IC50 of 0.629 mM. The molecular docking data showed that emodin could bind tightly to the active site of ADA. Our results demonstrated that emodin displayed a new biological activity which is ADA inhibitory activity with high cytotoxic activity against K562 leukemia cells. The bioactivity of cordycepin was significantly increased when used in combination with emodin.Conclusion:Emodin may represent a good candidate anti-cancer therapy and adenosine protective agent.
Funder
Gansu Food and Drug Research Project
Fundamental Research Funds for Key Laboratories of Drug Screening and Deep Processing for Traditional Chinese and Tibetan Medicine of Gansu Province
Gansu Province Natural Science Fund
National Natural Science Foundation of China
Publisher
Bentham Science Publishers Ltd.
Subject
Organic Chemistry,Computer Science Applications,Drug Discovery,General Medicine
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