Journal Article

Neuroprotective, and memory enhancement effects of Salvia aristata and its phenolic constituents: an in vitro, and in vivo study

Dabaghian, Farid, Akbarzadeh, Tahmineh, Sharifzadeh, Mohammad, Delnavazi, Mohammad-Reza, Khanavi, Mahnaz, Shams Ardekani, Mohammad Reza, Hariri, Roshanak, Tayarani-Najaran, Zahra

2025

Overview

Background Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cholinergic dysfunction, neuroinflammation, oxidative stress, and memory impairment. The Salvia genus has been used since ancient times for its anti-inflammatory and neuroprotective properties. In this study, we aimed to investigate the effects of Salvia aristata hydroalcoholic extract (SAHE) and dichloromethane extract (SADE) on various aspects of memory and AD. Methods Column chromatography was utilized in the phytochemical analysis to isolate and purify bioactive compounds. The structures of the isolated compounds were determined through spectroscopic techniques, including 1D and 2D NMR, along with IR, UV, and HRESIMS for the new compound. Cholinesterase inhibitory activity was assessed using a modified Ellman’s method. Additionally, the antioxidant activity and metal chelation capacity of SAHE and SADE were evaluated using the DPPH assay and spectroscopic methods, respectively. Moreover, the neuroprotective effects in PC12 cells were investigated using the AlamarBlue assay, and the ability to mitigate scopolamine-induced memory impairment in rats was assessed using the Morris water maze (MWM) test. Results In this study, we isolated and structurally elucidated an undescribed compound, namely salvinarin ( 2 ), as well as four known compounds including linariin ( 1 ), pectolinarin ( 3 ), scutellarein 4’-O-methyl-7-O-rutinoside ( 4 ), and 5-O-coumaroylquinic acid ( 5 ) from SAHE for the first time. In vitro analyses revealed that SAHE, SADE, and linariin exhibited significant neuroprotective effects against H 2 O 2 -induced cytotoxicity in PC12 cells. Notably, SAHE demonstrated potent acetylcholinesterase (AChE) inhibition (IC 50  = 322.83 ± 1.11 µ g/mL), significant antioxidant activity (IC 50  = 99.16 ± 1.24 µ g/mL), and strong metal chelating capacity toward Cu 2+ , Zn 2+ , and Fe 2+ . Moreover, oral administration of SAHE (400 mg/kg/day) significantly ameliorated memory impairment induced by scopolamine in a rat model. This improvement was evident in parameters such as traveled distance ( p  < 0.001), escape latency ( p  < 0.001), and time spent in the target quadrant ( p  < 0.01) in the Morris water maze test. Conclusions Considering all findings, including significant neuroprotective, antioxidant, and metal-chelating properties, alongside notable efficacy in enhancing memory in rat models, S. aristata could be a potential candidate for memory improvement. Graphical Abstract

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Acetylcholinesterase / Advertising executives / Alzheimer Disease - drug therapy / Alzheimer's disease / Animal cognition / Animal models / Animals / antioxidant activity / Antioxidants / Antioxidants - pharmacology / Bioactive compounds / Biocompatibility / Chelation / Chiropractic Medicine / Cholinergics / Cholinesterase / Cholinesterase Inhibitors - pharmacology / Chromatography / Column chromatography / complement / Complementary & Alternative Medicine / Cytotoxicity / Dichloromethane / Flavonoid / genus / Herbal medicine / Hydrogen peroxide / Impairment / In vivo methods and tests / Inflammation / Internal Medicine / Investigations / Iran / Lamiaceae / Latency / Male / Medicine / Medicine & Public Health / Memory / Memory - drug effects / memory disorders / Memory Disorders - drug therapy / methylene chloride / Natural resources / Nervous system diseases / Neurodegenerative diseases / Neuroprotection / Neuroprotective Agents - chemistry / Neuroprotective Agents - pharmacology / NMR / Nuclear magnetic resonance / Oral administration / Oxidative stress / Pathophysiology / PC12 Cells / Phenolic compounds / Phenols - chemistry / Phenols - pharmacology / Pheochromocytoma cells / phytochemicals / Plant Extracts - chemistry / Plant Extracts - pharmacology / Polyphenols / Potassium / Rats / Rats, Sprague-Dawley / Salvia / Salvia - chemistry / Salvia aristata / Scopolamine / spectroscopy / Zinc