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Monoamine Oxidase Inhibition by Major Tanshinones from Salvia miltiorrhiza and Selective Muscarinic Acetylcholine M4 Receptor Antagonism by Tanshinone I.
Prajapati, Ritu; Park, Se Eun; Seong, Su Hui; Paudel, Pradeep; Fauzi, Fazlin Mohd; Jung, Hyun Ah; Choi, Jae Sue.
Afiliação
  • Prajapati R; Department of Food and Life Science, Pukyong National University, Busan 48513, Korea.
  • Park SE; Department of Food and Life Science, Pukyong National University, Busan 48513, Korea.
  • Seong SH; Department of Biomedical Science, Asan Medical Institute of Convergence Science and Technology, University of Ulsan, Seoul 05505, Korea.
  • Paudel P; Department of Food and Life Science, Pukyong National University, Busan 48513, Korea.
  • Fauzi FM; Natural Product Research Division, Honam National Institute of Biological Resource, Mokpo 58762, Korea.
  • Jung HA; Department of Food and Life Science, Pukyong National University, Busan 48513, Korea.
  • Choi JS; National Center for Natural Products Research, Research Institute of Pharmaceutical Science, The University of Mississippi, Oxford, MS 38677, USA.
Biomolecules ; 11(7)2021 07 08.
Article em En | MEDLINE | ID: mdl-34356625
Monoamine oxidases (MAOs) and muscarinic acetylcholine receptors (mAChRs) are considered important therapeutic targets for Parkinson's disease (PD). Lipophilic tanshinones are major phytoconstituents in the dried roots of Salvia miltiorrhiza that have demonstrated neuroprotective effects against dopaminergic neurotoxins and the inhibition of MAO-A. Since MAO-B inhibition is considered an effective therapeutic strategy for PD, we tested the inhibitory activities of three abundant tanshinone congeners against recombinant human MAO (hMAO) isoenzymes through in vitro experiments. In our study, tanshinone I (1) exhibited the highest potency against hMAO-A, followed by tanshinone IIA and cryptotanshinone, with an IC50 less than 10 µM. They also suppressed hMAO-B activity, with an IC50 below 25 µM. Although tanshinones are known to inhibit hMAO-A, their enzyme inhibition mechanism and binding sites have yet to be investigated. Enzyme kinetics and molecular docking studies have revealed the mode of inhibition and interactions of tanshinones during enzyme inhibition. Proteochemometric modeling predicted mAChRs as possible pharmacological targets of 1, and in vitro functional assays confirmed the selective M4 antagonist nature of 1 (56.1% ± 2.40% inhibition of control agonist response at 100 µM). These findings indicate that 1 is a potential therapeutic molecule for managing the motor dysfunction and depression associated with PD.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fenantrenos / Salvia miltiorrhiza / Abietanos / Receptor Muscarínico M4 / Monoaminoxidase / Inibidores da Monoaminoxidase Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Biomolecules Ano de publicação: 2021 Tipo de documento: Article País de publicação: Suíça

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fenantrenos / Salvia miltiorrhiza / Abietanos / Receptor Muscarínico M4 / Monoaminoxidase / Inibidores da Monoaminoxidase Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Biomolecules Ano de publicação: 2021 Tipo de documento: Article País de publicação: Suíça