Furofuranoid-Type Lignans and Related Phenolics from IAnisacanthus virgularis/I Nees with Promising Anticholinesterase and Anti-Ageing Properties: A Study Supported by Molecular Modelling

• Published in: Plants (Basel) Vol. 13; no. 2
• Main Authors: Orabi, Mohamed A. A, Abdelhamid, Reda A, Elimam, Hanan, Elshaier, Yaseen A. M. M, Ali, Ahmed A, Aldabaan, Nayef, Alhasaniah, Abdulaziz Hassan, Refaey, Mohamed S
• Format: Journal Article
• Language: English
• Published: MDPI AG 01.01.2024
• Subjects: Alzheimer's disease; Chemical properties; Cholinesterase inhibitors; Drug therapy; Health aspects; Pharmaceutical research; Pharmacology, Experimental; Phenols; Saudi Arabia
• ISSN: 2223-7747; 2223-7747
• DOI: 10.3390/plants13020150

Lignan phytomolecules demonstrate promising anti-Alzheimer activity by alleviating dementia and preserving nerve cells. The purpose of this work is to characterize the lignans of Anisacanthus virgularis and explore their potential anti-acetylcholinesterase and anti-ageing effects. Phytochemical investigation of A. virgularis aerial parts afforded a new furofuranoid-type lignan (1), four known structural analogues, namely pinoresinol (2), epipinoresinol (3), phillyrin (4), and pinoresinol 4-O-β-d-glucoside (5), in addition to p-methoxy-trans-methyl cinnamate (6) and 1H-indole-3-carboxaldehyde (7). The structures were established from thorough spectroscopic analyses and comparisons with the literature. Assessment of the anticholinesterase activity of the lignans 1–5 displayed noticeable enzyme inhibition of 1 (IC[sub.50] = 85.03 ± 4.26 nM) and 5 (64.47 ± 2.75 nM) but lower activity of compounds 2–4 as compared to the reference drug donepezil. These findings were further emphasized by molecular docking of 1 and 5 with acetylcholinesterase (AChE). Rapid overlay chemical similarity (ROCS) and structure–activity relationships (SAR) analysis highlighted and rationalized the anti-AD capability of these compounds. Telomerase activation testing of the same isolates revealed 1.64-, 1.66-, and 1.72-fold activations in cells treated with compounds 1, 5, and 4, respectively, compared to untreated cells. Our findings may pave the way for further investigations into the development of anti-Alzheimer and/or anti-ageing drugs from furofuranoid-type lignans.