Monoamine Oxidase Inhibition by Major Tanshinones from Salvia miltiorrhiza and Selective Muscarinic Acetylcholine M4 Receptor Antagonism by Tanshinone I

Monoamine oxidases (MAOs) and muscarinic acetylcholine receptors (mAChRs) are considered important therapeutic targets for Parkinson’s disease (PD). Lipophilic tanshinones major phytoconstituents in the dried roots of Salvia miltiorrhiza that have demonstrated neuroprotective effects against dopaminergic neurotoxins inhibition MAO-A. Since MAO-B is an effective strategy PD, we tested inhibitory activities three abundant tanshinone congeners recombinant human MAO (hMAO) isoenzymes through vitro experiments. In our study, I (1) exhibited highest potency hMAO-A, followed by IIA cryptotanshinone, with IC50 less than 10 µM. They also suppressed hMAO-B activity, below 25 Although known to inhibit their enzyme mechanism binding sites yet be investigated. Enzyme kinetics molecular docking studies revealed mode interactions during inhibition. Proteochemometric modeling predicted mAChRs as possible pharmacological 1, functional assays confirmed selective M4 antagonist nature 1 (56.1% ± 2.40% control agonist response at 100 µM). These findings indicate a potential molecule managing motor dysfunction depression associated PD.