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

Abstract 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....

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Main Authors: Farid Dabaghian, Mohammad-Reza Delnavazi, Roshanak Hariri, Tahmineh Akbarzadeh, Zahra Tayarani-Najaran, Mohammad Reza Shams Ardekani, Mohammad Sharifzadeh, Mahnaz Khanavi
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Language:English
Published: BMC 2025-05-01
Series:BMC Complementary Medicine and Therapies
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Online Access:https://doi.org/10.1186/s12906-025-04902-1
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author Farid Dabaghian
Mohammad-Reza Delnavazi
Roshanak Hariri
Tahmineh Akbarzadeh
Zahra Tayarani-Najaran
Mohammad Reza Shams Ardekani
Mohammad Sharifzadeh
Mahnaz Khanavi
author_facet Farid Dabaghian
Mohammad-Reza Delnavazi
Roshanak Hariri
Tahmineh Akbarzadeh
Zahra Tayarani-Najaran
Mohammad Reza Shams Ardekani
Mohammad Sharifzadeh
Mahnaz Khanavi
author_sort Farid Dabaghian
collection DOAJ
description Abstract 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 H2O2-induced cytotoxicity in PC12 cells. Notably, SAHE demonstrated potent acetylcholinesterase (AChE) inhibition (IC50 = 322.83 ± 1.11 µg/mL), significant antioxidant activity (IC50 = 99.16 ± 1.24 µg/mL), and strong metal chelating capacity toward Cu2+, Zn2+, and Fe2+. 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
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spelling doaj-art-806ec216ed1b47a19a6a5cc8d873c4de2025-08-20T03:53:58ZengBMCBMC Complementary Medicine and Therapies2662-76712025-05-0125111810.1186/s12906-025-04902-1Neuroprotective, and memory enhancement effects of Salvia aristata and its phenolic constituents: an in vitro, and in vivo studyFarid Dabaghian0Mohammad-Reza Delnavazi1Roshanak Hariri2Tahmineh Akbarzadeh3Zahra Tayarani-Najaran4Mohammad Reza Shams Ardekani5Mohammad Sharifzadeh6Mahnaz Khanavi7Department of Pharmacognosy, Faculty of Pharmacy, and Persian Medicine and Pharmacy Research Center, Tehran University of Medicine SciencesDepartment of Pharmacognosy, Faculty of Pharmacy, and Persian Medicine and Pharmacy Research Center, Tehran University of Medicine SciencesDepartment of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical SciencesDepartment of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical SciencesTargeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical SciencesDepartment of Pharmacognosy, Faculty of Pharmacy, and Persian Medicine and Pharmacy Research Center, Tehran University of Medicine SciencesDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical SciencesDepartment of Pharmacognosy, Faculty of Pharmacy, and Persian Medicine and Pharmacy Research Center, Tehran University of Medicine SciencesAbstract 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 H2O2-induced cytotoxicity in PC12 cells. Notably, SAHE demonstrated potent acetylcholinesterase (AChE) inhibition (IC50 = 322.83 ± 1.11 µg/mL), significant antioxidant activity (IC50 = 99.16 ± 1.24 µg/mL), and strong metal chelating capacity toward Cu2+, Zn2+, and Fe2+. 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 Abstracthttps://doi.org/10.1186/s12906-025-04902-1Salvia aristataLamiaceaeFlavonoidPolyphenolsAlzheimer’s diseaseMemory
spellingShingle Farid Dabaghian
Mohammad-Reza Delnavazi
Roshanak Hariri
Tahmineh Akbarzadeh
Zahra Tayarani-Najaran
Mohammad Reza Shams Ardekani
Mohammad Sharifzadeh
Mahnaz Khanavi
Neuroprotective, and memory enhancement effects of Salvia aristata and its phenolic constituents: an in vitro, and in vivo study
BMC Complementary Medicine and Therapies
Salvia aristata
Lamiaceae
Flavonoid
Polyphenols
Alzheimer’s disease
Memory
title Neuroprotective, and memory enhancement effects of Salvia aristata and its phenolic constituents: an in vitro, and in vivo study
title_full Neuroprotective, and memory enhancement effects of Salvia aristata and its phenolic constituents: an in vitro, and in vivo study
title_fullStr Neuroprotective, and memory enhancement effects of Salvia aristata and its phenolic constituents: an in vitro, and in vivo study
title_full_unstemmed Neuroprotective, and memory enhancement effects of Salvia aristata and its phenolic constituents: an in vitro, and in vivo study
title_short Neuroprotective, and memory enhancement effects of Salvia aristata and its phenolic constituents: an in vitro, and in vivo study
title_sort neuroprotective and memory enhancement effects of salvia aristata and its phenolic constituents an in vitro and in vivo study
topic Salvia aristata
Lamiaceae
Flavonoid
Polyphenols
Alzheimer’s disease
Memory
url https://doi.org/10.1186/s12906-025-04902-1
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