β-pinene ameliorates ICV-STZ induced Alzheimer's pathology via antioxidant, anticholinesterase, and mitochondrial protective effects: In-silico and in-vivo studies

Mini Dahiya; Anil Kumar; Monu Yadav; Shilpi Chauhan

doi:10.1016/j.ejphar.2025.177307

β-pinene ameliorates ICV-STZ induced Alzheimer's pathology via antioxidant, anticholinesterase, and mitochondrial protective effects: In-silico and in-vivo studies

Eur J Pharmacol. 2025 Jan 25:177307. doi: 10.1016/j.ejphar.2025.177307. Online ahead of print.

Authors

Mini Dahiya¹, Anil Kumar², Monu Yadav³, Shilpi Chauhan⁴

Affiliations

¹ University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies (UGC-CAS), Panjab University, Chandigarh 160014, India.
² University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies (UGC-CAS), Panjab University, Chandigarh 160014, India. Electronic address: kumaruips@yahoo.com.
³ Amity Institute of Pharmacy, Amity University, Haryana, Amity Education Valley Gurugram, Manesar, Panchgaon, Haryana, India.
⁴ Department of Pharmacy, Lloyd Institute of Management and Technology, Plot No.-11, Knowledge Park-II, Greater Noida, Uttar Pradesh, India-201306.

PMID: 39870228
DOI: 10.1016/j.ejphar.2025.177307

Abstract

Introduction: Alzheimer's disease (AD) is a leading cause of dementia, characterized by progressive neurodegeneration and cognitive dysfunction. The disease aetiology is closely associated with proteinopathies, mitochondrial abnormalities, and elevated ROS generation, which are some of the primary markers for AD brains.

Objectives: The current research was intended to elucidate the chemical interaction of β-pinene against potential targets and evaluate its neuroprotective potential in ICV-STZ-induced sAD.

Method: ology: The potential binding interactions of β-pinene and galantamine were evaluated against the active sites of PP2A, SOD1, catalase-3, and AChE using Autodock vina. Additionally, the β-pinene and galantamine were subjected to tests of their ADMET by employing the Swiss ADME and Protox-II web servers. To assess the neuroprotective potential, β-pinene (50, 100, and 200 mg/kg) and galantamine (2 mg/kg) was administered p.o in ICV-STZ-treated wistar rats for 21 days. Moreover, behavioral parameters (NOR & MWM), biochemical, AChE activities, and mitochondrial complexes were performed.

Results: A molecular docking study showed that β-pinene can interact with human PP2A, SOD1, Catalase-3, and AChE with better ligand efficiency as compared to galantamine. In-vivo data showed that β-pinene treatment (100, and 200 mg/kg) for 21 days exhibited significantly enhanced cognitive performance, as shown in behavioral studies. Additionally, β-pinene treatment significantly re-established antioxidant levels and mitochondrial capacities and attenuated altered AChE activity as compared to ICV-STZ-induced groups.

Conclusions: In-silico studies revealed that β-pinene shared the same binding pocket as galantamine, supporting its neuroprotective effects in the ICV-STZ-induced animal model by alleviating oxidative stress and mitochondrial dysfunction and reducing AChE activity.

Keywords: Alzheimer’s disease; Antioxidants; In-Silico; Memory; Mitochondrial dysfunction; Streptozotocin; β-pinene.