Hemp bark extract attenuates scopolamine-induced cognitive dysfunction through multi-target cholinesterase, MAO-B, and antioxidant mechanisms.
6 affiliations
- 1Research Institute, K-medichem Co., Ltd., Chuncheon, 24341, Republic of Korea.
- 2Metropolitan Seoul Center, Korea Basic Science Institute, Seoul, Republic of Korea.
- 3OBMC Lab, Smart-Healthcare Convergence Major, Hallym University, Chuncheon, 24252, Republic of Korea.
- 4Multidisciplinary Genome Institute, Hallym University, Chuncheon, 24252, Republic of Korea.
- 5Hallym AI-Biohealth R&BD Center, Hallym University, Chuncheon, 24252, Republic of Korea.
- 6Department of Bio-Health Technology, College of Biomedical Science, Kangwon National University, Chuncheon, 24341, Republic of Korea.
Abstract
Cognitive decline associated with Alzheimer's disease is driven by several interconnected mechanisms, including impaired cholinergic signaling, MAO-B-linked oxidative stress, and reduced neuronal antioxidant capacity. In this study, ethanol extracts prepared from hemp root, stem, bark, leaf, and seed were compared to identify hemp-derived materials with multi-target neuroprotective potential. Among the tested extracts, hemp bark extract (HBE) showed the most balanced activity profile, inhibiting acetylcholinesterase, butyrylcholinesterase, and MAO-B with IC50 values of 0.56, 0.01, and 0.02 mg/mL, respectively. HBE at 0.2 μg/mL suppressed H2O2-induced intracellular reactive oxygen species formation and recovered superoxide dismutase activity in SH-SY5Y neuronal cells. In a scopolamine-induced mouse model, oral HBE administration at 100 and 200 mg/kg improved performance in the passive avoidance test and reduced escape latency in the water maze test, indicating protection against scopolamine-induced cognitive deficits. Chemical profiling by ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry revealed several cannabinoids in HBE, including cannabidiol, cannabidiolic acid, and cannabichromenic acid. Enzyme assays showed that cannabichromenic acid potently inhibited acetylcholinesterase and butyrylcholinesterase, with IC50 values of 1.3 and 6.6 μM, respectively, whereas cannabidiol and cannabidiolic acid were the most active MAO-B inhibitors, with IC50 values of 2.3 and 5.3 μM. Docking, GNINA rescoring, molecular dynamics simulations, and MM-GBSA/MM-PBSA analyses further supported stable interactions of these cannabinoids with the target enzymes, particularly cannabidiolic acid with acetylcholinesterase and MAO-B. These findings suggest that HBE protects against scopolamine-induced cognitive dysfunction through coordinated cholinesterase inhibition, MAO-B modulation, and antioxidant defense, with cannabidiol, cannabidiolic acid, and cannabichromenic acid acting as key multi-target constituents.
Related
- Ishige foliacea Water Extract (KDC22-01) Attenuates Tau Hyperphosphorylation and Ameliorates Scopolamine-Induced Memory Impairment in Mice
- Phytochemical Phenolic Profile, Cholinesterase and α-Glucosidase Inhibitory Activities Rationalized by Molecular Docking, and Antioxidant Capacity of Hibiscus sabdariffa.
- Gui Gan Shen Mai Yin attenuates cardiac hypertrophy and dysfunction in association with mitochondrial homeostasis and the PI3K/AKT1 signaling pathway
- Integrated Metabolomics Identifies Mitochondrial Dysfunction, Oxidative Membrane Remodeling, and Reduced Lipophilic Antioxidant Defenses in First-Episode Simple Dysmood Disorder
- Pear Peel–Enriched Residue Extract Attenuates Ethanol‐Induced Liver Injury Through Regulation of Antioxidant Signaling and Lipid Metabolism
BibTeX
@article{heo2026hemp,
title = {{Hemp bark extract attenuates scopolamine-induced cognitive dysfunction through multi-target cholinesterase, MAO-B, and antioxidant mechanisms.}},
author = {Hee-Young Heo and Jae Kwon Kim and SeonJu Park and Keum-Soo Song and Satish Balasaheb Nimse and Kooyeon Lee},
journal = {Biochemistry and biophysics reports},
year = {2026},
month = oct,
doi = {10.1016/j.bbrep.2026.102852},
url = {https://europepmc.org/article/MED/42997626},
note = {CC BY},
}
RIS
TY - JOUR
TI - Hemp bark extract attenuates scopolamine-induced cognitive dysfunction through multi-target cholinesterase, MAO-B, and antioxidant mechanisms.
AU - Hee-Young Heo
AU - Jae Kwon Kim
AU - SeonJu Park
AU - Keum-Soo Song
AU - Satish Balasaheb Nimse
AU - Kooyeon Lee
PY - 2026
DA - 2026/10/28
JO - Biochemistry and biophysics reports
DO - 10.1016/j.bbrep.2026.102852
UR - https://europepmc.org/article/MED/42997626
AB - Cognitive decline associated with Alzheimer's disease is driven by several interconnected mechanisms, including impaired cholinergic signaling, MAO-B-linked oxidative stress, and reduced neuronal antioxidant capacity. In this study, ethanol extracts prepared from hemp root, stem, bark, leaf, and seed were compared to identify hemp-derived materials with multi-target neuroprotective potential. Among the tested extracts, hemp bark extract (HBE) showed the most balanced activity profile, inhibiting acetylcholinesterase, butyrylcholinesterase, and MAO-B with IC50 values of 0.56, 0.01, and 0.02 mg/mL, respectively. HBE at 0.2 μg/mL suppressed H2O2-induced intracellular reactive oxygen species formation and recovered superoxide dismutase activity in SH-SY5Y neuronal cells. In a scopolamine-induced mouse model, oral HBE administration at 100 and 200 mg/kg improved performance in the passive avoidance test and reduced escape latency in the water maze test, indicating protection against scopolamine-induced cognitive deficits. Chemical profiling by ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry revealed several cannabinoids in HBE, including cannabidiol, cannabidiolic acid, and cannabichromenic acid. Enzyme assays showed that cannabichromenic acid potently inhibited acetylcholinesterase and butyrylcholinesterase, with IC50 values of 1.3 and 6.6 μM, respectively, whereas cannabidiol and cannabidiolic acid were the most active MAO-B inhibitors, with IC50 values of 2.3 and 5.3 μM. Docking, GNINA rescoring, molecular dynamics simulations, and MM-GBSA/MM-PBSA analyses further supported stable interactions of these cannabinoids with the target enzymes, particularly cannabidiolic acid with acetylcholinesterase and MAO-B. These findings suggest that HBE protects against scopolamine-induced cognitive dysfunction through coordinated cholinesterase inhibition, MAO-B modulation, and antioxidant defense, with cannabidiol, cannabidiolic acid, and cannabichromenic acid acting as key multi-target constituents.
SN - 2405-5808
ER -