Potential Anti-Acetylcholinesterase Activity of <i>Cassia timorensis</i> DC.

• Main Authors: Nurul Amira Nurul Azman, Maram B. Alhawarri, Mira Syahfriena Amir Rawa, Roza Dianita, Amirah Mohd Gazzali, Toshihiko Nogawa, Habibah A. Wahab
• Format: Article
• Language: English
• Published: MDPI AG 2020-10-01
• Series: Molecules
• Subjects: <i>Cassia timorensis</i>; <i>Senna timoriensis</i>; benzenepropanoic acid; 9,12,15-octadecatrienoic acid; 3-methoxyquercetin; acetylcholinesterase
• Online Access: https://www.mdpi.com/1420-3049/25/19/4545

Seventeen methanol extracts from different plant parts of five different <i>Cassia</i> species, including <i>C. timorensis</i>, <i>C. grandis</i>, <i>C. fistula</i>, <i>C. spectabilis</i>, and <i>C. alata</i> were screened against acetylcholinesterase (AChE). <i>C. timorensis</i> extracts were found to exhibit the highest inhibition towards AChE whereby the leaf, stem, and flower methanol extracts showed 94–97% inhibition. As far as we are aware, <i>C. timorensis</i> is one of the least explored <i>Cassia</i> spp. for bioactivity. Further fractionation led to the identification of six compounds, isolated for the first time from <i>C. timorensis</i>: 3-methoxyquercetin (<b>1</b>), benzenepropanoic acid (<b>2</b>), 9,12,15-octadecatrienoic acid (<b>3</b>), β-sitosterol (<b>4</b>), stigmasterol (<b>5</b>), and 1-octadecanol (<b>6</b>). Compound <b>1</b> showed moderate inhibition towards AChE (IC₅₀: 83.71 μM), while the other compounds exhibited poor to slightly moderate AChE inhibitory activity. Molecular docking revealed that the methoxy substitution of <b>1</b> formed a hydrogen bond with TYR121 at the peripheral anionic site (PAS) and the hydroxyl group at C5 formed a covalent hydrogen bond with ASP72. Additionally, the OH group at the C3′ position formed an interaction with the protein at the acyl pocket (PHE288). This possibly explains the activity of <b>1</b> in blocking the entry of acetylcholine (ACh, the neurotransmitter), thus impeding the hydrolysis of ACh.