In vitro and in silico analysis of Solanum torvum fruit and methyl caffeate interaction with cholinesterases

Maha Aljabri; Khadiga Alharbi; Mona Alonazi

doi:10.1016/j.sjbs.2023.103815

In vitro and in silico analysis of Solanum torvum fruit and methyl caffeate interaction with cholinesterases

Saudi J Biol Sci. 2023 Oct;30(10):103815. doi: 10.1016/j.sjbs.2023.103815. Epub 2023 Sep 20.

Authors

Maha Aljabri¹, Khadiga Alharbi², Mona Alonazi³

Affiliations

¹ Department of Biology, Faculty of Applied Science, Umm Al-Qura University, Makkah, Saudi Arabia.
² Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia.
³ Biochemistry Department, College of Science, King Saud University, Riyadh 11495, Saudi Arabia.

Abstract

Oxidative stress along with dysfunction in cholinergic neurotransmission primarily underlies cognitive impairment. A significant approach to mitigate cognitive dysfunction involves the inhibition of cholinesterases, namely acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Exploring the potential antioxidant and anticholinesterase effects of edible plants holds promise for their utilization as botanicals to enhance cognition. Solanum torvum fruit with vast biological properties are used as food. In the present study, butanolic extract of S. torvum fruits (BESTF) was prepared. Additionally, the study investigated into the properties of methyl caffeate (MC), a compound present in S. torvum, obtained in its pure form. In vitro antioxidant and anticholinesterases activity of BESTF and MC were determined. BESTF and MC showed potent antioxidant property. BESTF and MC dose-dependently inhibited AChE (IC₅₀ values: 166.6 µg/ml and 680.6 µM, respectively) and BChE (IC₅₀ values: 161.55 µg/ml and 413 µM, respectively). BESTF and MC inhibited AChE and BChE in competitive mode. Active site gorge of AChE/BChE was occupied by MC which formed interaction with amino acids present in catalytic site and PAS in in silico. Further, molecular dynamics simulations followed by free energy calculation, principal component analysis and dynamic cross-correlation matrix provided the compelling evidence that that MC maintained stable interactions during MD simulation with AChE and BChE. Collectively, the results from the present study underlines the cognitive-enhancing effect of BESTF and MC.

Keywords: Acetylcholinesterase; Antioxidant; Butyrylcholinesterase; Methyl caffeate; Molecular dynamics; Solanum torvum.