Ailanthus altissima Extract Ameliorates Cognitive Declineand Neurodegeneration in an Aluminum Chloride–InducedRat Model of Alzheimer’s Disease

:Title

Ailanthus altissima Extract Ameliorates Cognitive Decline and Neurodegeneration in an Aluminum Chloride-Induced Rat Model of Alzheimer's Disease

Authors: 

Mohammad Mehdi Gravandi, Daniel Elieh-Ali-Komi, Roshanak Amirian, Seyede Zahra Hosseini, Seyede Darya Alavi, Samira Shirooie, Amir Kiani, Mohammad Hosein Farzaei

Year: 2026

:Abstract

Background: The extract of Ailanthus altissima possesses anti-inflammatory and neuroprotective properties. We aimed to investigate its effectiveness in mitigating the AlCl3-induced Alzheimer's disease in a rat model.
Methods: A total of 32 adult male Wistar rats were divided into 4 groups each consisting of 8 rats. The control group received saline and the AlCl3 group received AlCl3 (0.2 cc 100 mg/kg intraperitoneal) for 14 days. Two other groups received either 50 or 100 mg/kg of Ailanthus altissima after AlCl3 treatment. Behavioral tests including open field test (OFT), elevated plus maze, and passive avoidance tests were performed. Nuclear factor kappa B (NF-κB), glial filamentous acidic protein (GFAP), and amyloid beta were stained using immunohistochemistry (IHC) in the hippocampus.Results: AlCl3 administration caused significant memory impairment, and treatment with Ailanthus altissima extract effectively mitigated these deficits in a dose-dependent manner. The effects were dose-dependent, and the group receiving 100 mg/kg extract presented the most significant results in the conducted behavioral tests. The IHC results for NF-κB showed that treatment with 50 mg/kg of extract significantly reduced NF-κB expression compared with the AlCl3 group (6.64% vs. 13.3% respectively, p < 0.05). A higher dose of 100 mg/kg resulted in an even greater reduction (4.45% vs. 13.3%, p < 0.01). Extract treatment reduced GFAP positivity in a dose-dependent manner, with the 50 mg/kg group showing a significant decrease to 11.8% (p < 0.05). The 100 mg/kg group demonstrated an even more substantial reduction to 7.7% (p < 0.01) compared with the AlCl3 group (18.65%). Amyloid beta positivity was critically reduced in the 100 mg/kg-receiving group.
Conclusions: Ailanthus altissima extract shows potential as a neuroprotective extract. It counteracts AlCl3-induced behavioral and neuropathological changes, suggesting promising therapeutic applications.  

Ferula ammoniacum gum aqueous extract exerts anti-inflammatory and antioxidant mechanisms to combat aluminum chloride-induced Alzheimer’s disease in rats

:Title

Ferula ammoniacum gum aqueous extract exerts anti-inflammatory and antioxidant mechanisms to combat aluminum chloride-induced Alzheimer's disease in rats: possible involvement of opioid pathways

Authors: 

Sajad Fakhri, Mohammad Mehdi Gravandi, Mohammad Bagher Majooni, Mohammad Hosein Farzaei, Fatemeh Abbaszadeh, Khodabakhsh Rashidi, Javier Echeverria 

Journal: Frontiers in Pharmacology (Front. Pharmacol.)

Year: 2026

Abstract:

Background: Alzheimer's disease (AD), the most common form of dementia, significantly affects memory and behavior due to dysregulated pathways involving oxidative stress, inflammation, and opioidergic systems. Currently, no effective treatments are available, underscoring the need for novel alternatives. Ferula ammoniacum (D.Don) Spalik, M. Panahi, Piwczynski, and Puchatka (Apiaceae) (FA), an Iranian medicinal plant, is known for its anti-seizure, anti-inflammatory, and analgesic properties, with its gum utilized as a nerve tonic.Purpose: This study investigates the anti-AD effects of F. ammoniacum gum aqueous extract (FAGAE) using an aluminum chloride (AlCl3)-induced Wistar rat model of AD.
Materials and methods: The aqueous extract, prepared by macerating powdered gum in distilled water for 48 h at ambient temperature, was subjected to phytochemical analysis using ultraviolet, infrared, and nuclear magnetic resonance spectroscopy. Thirty rats were assigned to five different groups: one receiving saline, one receiving AlCl3 (100 mg/kg, i.p.), two receiving AlCl3 followed by oral treatment with FAGAE at doses of 50 or 100 mg/kg, and one receiving naloxone (an opioid receptor antagonist) along with AlCl3 and the effective dose of FAGAE. Behavioral changes were evaluated using the open-field, passive avoidance, and elevated plus maze tests. Furthermore, biochemical analyses were conducted to measure the serum nitrite levels, changes in weight, matrix metalloproteinase (MMP) activity, and histopathological changes in brain tissue.
Results and discussion: The phytochemical analysis of FAGAE revealed the presence of polysaccharide compounds with tentative arabinogalactan structures. FAGAE decreased step-through latency in the passive avoidance test and modified AlCl3-induced weight changes. FAGAE also significantly increased mobility, grooming, and crossing in the open-field test. Naloxone reversed the anti-AD effects of FAGAE, suggesting a possible role for opioidergic pathways in its therapeutic effects. Zymography results showed that FAGAE reduced MMP-9 activity while increasing MMP-2 activity. Histopathological analysis revealed a preserved number of intact neurons in the hippocampus, whereas reduced serum nitrite levels were observed after FAGAE administration in rats with AD.
Conclusion: Behavioral, biochemical, and histopathological impairments induced by AlCl3 were significantly attenuated by FAGAE, possibly through the opioidergic pathway, which combats inflammation and oxidative stress and supports neuronal survival. 

Natural products attenuate PI3K-Akt-mTOR signaling pathway A promising strategy in regulating neurodegeneration

:Title

Natural products attenuate PI3K/Akt/mTOR signaling pathway: A promising strategy in regulating neurodegeneration

Authors:

Sajad Fakhri, Amin Iranpanah, Mohammad Mehdi Gravandi, Seyed Zachariah Moradi, Mohammad Ranjbari, Mohammad Bagher Majnooni, Javier Echeverria, Yaping Qi, Mingfu Wang, Pan Liao, Mohammad Hosein Farzaei, Jianbo Xiao

Journal: Phytomedicine
Year: 2021

Abstract:
Year: 2021Background: As common, progressive, and chronic causes of disability and death, neurodegenerative diseases (NDDs) significantly threaten human health, while no effective treatment is available. Given the engagement of multiple dysregulated pathways in neurodegeneration, there is an imperative need to target the axis and provide effective/multi-target agents to tackle neurodegeneration. Recent studies have revealed the role of phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) in some diseases and natural products with therapeutic potentials.
Purpose: This is the first systematic and comprehensive review on the role of plant-derived secondary metabolites in managing and/or treating various neuronal disorders via the PI3K/Akt/mTOR signaling pathway.
Study design and methods: A systematic and comprehensive review was done based on the PubMed, Scopus, Web of Science, and Cochrane electronic databases. Two independent investigators followed the PRISMA guidelines and included papers on PI3K/Akt/mTOR and interconnected pathways/mediators targeted by phytochemicals in NDDs.Results: Natural products are multi-target agents with diverse pharmacological and biological activities and rich sources for discovering and developing novel therapeutic agents. Accordingly, recent studies have shown increasing phytochemicals in combating Alzheimer's disease, aging, Parkinson's disease, brain/spinal cord damages, depression, and other neuronal-associated dysfunctions. Amongst the emerging targets in neurodegeneration, PI3K/Akt/mTOR is of great importance. Therefore, attenuation of these mediators would be a great step towards neuroprotection in such NDDs.
Conclusion: The application of plant-derived secondary metabolites in managing and/or treating various neuronal disorders through the PI3K/Akt/mTOR signaling pathway is a promising strategy towards neuroprotection. 

Protective effect of a hydromethanolic extract from Fraxinus excelsior L. bark against a rat model of aluminum chloride-induced Alzheimer's disease

:Title

Protective effect of a hydromethanolic extract from Fraxinus excelsior L. bark against a rat model of aluminum chloride-induced Alzheimer's disease: Relevance to its anti-inflammatory and antioxidant effects

 Authors:

Amin Iranpanah, Sajad Fakhri, Gholamreza Bahrami, Mohammad Bagher Majnooni, Mohammad Mehdi Gravandi, Sara Taghavi, Mehdi Azadi Badrbani, Roshanak Amirian, Mohammad Hosein Farzaei

Journal: Journal of Ethnopharmacology (J. Ethnopharmacol.)

Year: 2024

Abstract: