Black tea and its theaflavin derivatives firmly inhibit acetylcholinesterase activity, possible implications in cholinergic neurodegenerative or muscular disorder.

Abstract Background Over-expression of acetylcholinesterase (AChE), a key enzyme-regulator of neurotransmitter acetylcholine leads to neurodegenerative-disorder, Alzheimer’s-disease/muscular-dysfunction. Aims Therefore, inhibition of AChE may restrict these diseases. Objectives Presently, black-tea was tested in-vitro/in-vivo on AChE activities. Methods Inhibitory-effects on purified-AChE was screened from ten pure tea-phytochemicals viz. epicatechin(EC), epigallocatechin(EGC), catechin-gallate(CG), epicatechin-gallate(ECG), Epigallocatechin-gallate(EGCG), gallocatechin-gallate(GCG), theaflavin(TF), theaflavin-monogallate(TFMG), theaflavin-digallate(TFDG), and gallic-acid. Results Among those, TFDG and TFMG showed promising dose-dependent (mixed-type manner.) inhibition of AChE (IC50 = 1.6µM and 3.3µM, respectively). The TF showed moderate inhibitory-effect (IC50 = 29µM). Tea galloyl-ester catechins, ECG/CG/EGCG/GCG inhibited AChE (IC50 = 41, 49, 67and 54 µM, respectively). In-vivo, arsenic-intoxicated (0.6 ppm/4-weeks) rat increase of cerebellum AChE was completely restored by black-tea-extract (TF-rich). Molecular-docking by AutoDock-PatchDock server (binding/stability/kinetic) of AchE (PDBid:4M0E) and the experimental-flavonoids (PubChem-3Dstructures) suggest, TFDG (lowest Atomic-Contact-Energy − 369.87, TFMG, -347.06 kcal/mol) hampers the enzyme catalytic-hydrolytic-action and nucleophilic-attack by SER203 supporting the in-vitro results. Conclusively, the finding is therapeutically beneficial for cholinergic neurodegenerative/muscular disorders.