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Hemp bark extract attenuates scopolamine-induced cognitive dysfunction through multi-target cholinesterase, MAO-B, and antioxidant mechanisms

Year: 2026

Type: article

Abstract: Alzheimer’s disease-related cognitive dysfunction involves cholinergic impairment, monoamine oxidase-B (MAO-B)-associated oxidative burden, and neuronal oxidative stress. Here, ethanol extracts from hemp root, stem, bark, leaf, and seed were screened to identify multi-target modulators of these pathways. Hemp bark extract (HBE) showed a balanced pharmacological profile, inhibiting acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and MAO-B with IC₅₀ values of 0.56, 0.01, and 0.02 mg/mL, respectively. HBE also reduced H₂O₂-induced reactive oxygen species accumulation, restored superoxide dismutase activity in SH-SY5Y neuronal cells, and improved scopolamine-induced deficits in passive avoidance and water maze tests. UPLC-QTOF-MS/MS analysis identified multiple cannabinoids in HBE, including cannabidiol (CBD), cannabidiolic acid (CBDA), and cannabichromenic acid (CBCA). Among the isolated cannabinoids, CBCA showed strong dual cholinesterase inhibition, with IC₅₀ values of 1.3 µM for AChE and 6.6 µM for BuChE, whereas CBD and CBDA were the most potent MAO-B inhibitors, with IC₅₀ values of 2.3 and 5.3 µM, respectively. Molecular docking, GNINA rescoring, 100 ns molecular dynamics simulations, and MM-GBSA/MM-PBSA analyses supported stable binding of these cannabinoids to the enzyme active sites. MM-GBSA analysis identified favorable binding of CBDA with AChE and MAO-B, with ΔGbind values of -28.42 and -47.63 kcal/mol, respectively, CBD with AChE and MAO-B, with values of -28.36 and -40.69 kcal/mol, respectively, and CBCA with MAO-B, with a value of -41.02 kcal/mol. These findings indicate that HBE attenuates scopolamine-induced cognitive dysfunction through complementary cholinesterase inhibition, MAO-B modulation, and antioxidant defense, with CBD, CBDA, and CBCA serving as major multi-target contributors.

Source: Biochemistry and Biophysics Reports

DOI: 10.1016/j.bbrep.2026.102852

Authors: Hee-Young Heo, Jae Kwon Kim, SeonJu Park, Keum-Soo Song, Satish Balasaheb Nimse, Kooyeon Lee

Institutions: Korea Basic Science Institute, Hallym University, Kangwon National University

Language: English

Topic: Cholinesterase and Neurodegenerative Diseases

Subfield: Pharmacology (medical)

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,700