Anti-Acetylcholinesterase Activities of Mono-Herbal Extracts and Exhibited Synergistic Effects of the Phytoconstituents: A Biochemical and Computational Study

• Main Authors: Acharya Balkrishna, Subarna Pokhrel, Meenu Tomer, Sudeep Verma, Ajay Kumar, Pradeep Nain, Abhishek Gupta, Anurag Varshney
• Format: Article
• Language: English
• Published: MDPI AG 2019-11-01
• Series: Molecules
• Subjects: alzheimer’s disease; anti-acetylcholinesterase activity; herbal extracts; hplc; synergistic effect; molecular docking
• Online Access: https://www.mdpi.com/1420-3049/24/22/4175

Alzheimer&#8217;s disease (AD), a neurodegenerative disease, is the most common form of dementia. Inhibition of acetylcholinesterase (AChE) is a common strategy for the treatment of AD. In this study, aqueous, hydro-methanolic, and methanolic extracts of five potent herbal extracts were tested for their in vitro anti-AChE activity. Among all, the <i>Tinospora cordifolia</i> (Giloy) methanolic fraction performed better with an IC₅₀ of 202.64 &#181;g/mL. Of the HPLC analyzed components of <i>T. cordifolia</i> (methanolic extract), palmatine and berberine performed better (IC₅₀ 0.66 and 0.94 &#181;g/mL, respectively) as compared to gallic acid and the tool compound &#8220;galantamine hydrobromide&#8221; (IC₅₀ 7.89 and 1.45 &#181;g/mL, respectively). Mode of inhibition of palmatine and berberine was non-competitive, while the mode was competitive for the tool compound. Combinations of individual alkaloids palmatine and berberine resulted in a synergistic effect for AChE inhibition. Therefore, the AChE inhibition by the methanolic extract of <i>T. cordifolia</i> was probably due to the synergism of the isoquinoline alkaloids. Upon molecular docking, it was observed that palmatine and berberine preferred the peripheral anionic site (PAS) of AChE, with &#960;-interactions to PAS residue Trp286, indicating that it may hinder the substrate binding by partially blocking the entrance of the gorge of the active site or the product release.