Anticholinesterase Activity of Eight Medicinal Plant Species: In Vitro and In Silico Studies in the Search for Therapeutic Agents against Alzheimer’s Disease

Abstract

Many Bangladeshi medicinal plants have been used to treat Alzheimer’s disease and other neurodegenerative diseases. In the present study, the anticholinesterase effects of eight selected Bangladeshi medicinal plant species were investigated. Species were selected based on the traditional uses against CNS-related diseases. Extracts were prepared using a gentle cold extraction method. In vitro cholinesterase inhibitory effects were measured by Ellman’s method in 96-well microplates. Blumea lacera (Compositae) and Cyclea barbata (Menispermaceae) were found to have the highest acetylcholinesterase inhibitory (IC50, 150 ± 11 and 176 ± 14 µg/mL, respectively) and butyrylcholinesterase inhibitory effect (IC50, 297 ± 13 and 124 ± 2 µg/mL, respectively). Cyclea barbata demonstrated competitive inhibition, where Blumea lacera showed an uncompetitive inhibition mode for acetylcholinesterase. Smilax guianensis (Smilacaceae) and Byttneria pilosa (Malvaceae) were also found to show moderate AChE inhibition (IC50, 205 ± 31 and 221 ± 2 µg/mL, respectively), although no significant BChE inhibitory effect was observed for extracts from these plant species. Among others, Thunbergia Grandiflora (Acanthaceae) and Mikania micrantha (Compositae) were found to display noticeable AChE (IC50, 252 ± 22 µg/mL) and BChE (IC50, 314 ± 15 µg/mL) inhibitory effects, respectively. Molecular docking experiment suggested that compounds 5-hydroxy-3,6,7,3′,4′-pentamethoxyflavone (BL4) and kaempferol-3-O-α-L-rhamnopyranosyl-(1⟶6)-β-D-glucopyranoside (BL5) from Blumea lacera bound stably to the binding groove of the AChE and BChE by hydrogen-bond interactions, respectively. Therefore, these compounds could be candidates for cholinesterase inhibitors. The present findings demonstrated that Blumea lacera and Cyclea barbata are interesting objects for further studies aiming at future therapeutics for Alzheimer’s disease.

Synthesis, Computational Pharmacokinetics Report, Conceptual DFT-Based Calculations and Anti-Acetylcholinesterase Activity of Hydroxyapatite Nanoparticles Derived From Acorus Calamus Plant Extract

“…Surprisingly, significant AChE inhibition activity results was observed in A. calamus mediated HAp NPs, suggesting that the preparation of HAp NPs from A. calamus rhizome extract enhanced the AChE inhibition. Similar observations were made by Uddin et al (2021) where the extracts of Blumea lacera, Cyclea barbata, Smilax guianensis and Byttneria Pilosa inhibited AChE with an IC50 values of 150 ± 11, 176 ± 14, 205 ± 31, and 221 ± 2 μg/ml respectively Uddin et al (2021). They also proved that the plant extracts selected in their study showed a promising effect in inhibiting AChE activity, wherein the present study has shown improvement in biological activities in the medicinal plants when in combination with nanoparticle.…”

Exploring the Artemisia Genus: An Insight into the Phytochemical and Multi-Biological Potential of A. campestris subsp. lednicensis (Spreng.) Greuter & Raab-Straube

“…In the correlation analysis, eriodictyol and hydroxytrimethoxyflavone II strongly correlated with the observed anti-cholinesterase inhibitory activity ( Figure 5 ). Our results also agree with the data reported by Uddin et al [ 53 ] and Uriarte-Pueyo and Calvo [ 54 ]. Tyrosinase plays a key role in the synthesis of melanin and is therefore a checkpoint in the treatment of hyperpigmentation [ 55 ].…”

Exploring the mechanisms of kaempferol in neuroprotection: Implications for neurological disorders

“…Neuroinflammation, driven by an increase in nitric oxide (NO), interleukin‐6 (IL‐6), interleukin‐1 (IL‐1), TNF‐α, and other cytotoxic chemicals, is another pathogenic mechanism in AD 78 . A deficiency of cholinergic neurons has also been observed in AD, with cholinergic deficiency linked to the cognitive impairment seen in AD due to the degeneration of cholinergic neurons in the basal forebrain 82 …”