Tabriz University of Medical Sciences Pharmaceutical Sciences 1735-403X 32 1 2026 01 07 Melissa officinalis Alleviates Cognitive Impairments in a Mouse Model of Accelerated Aging; Possible Involvement of the Hippocampal Sirt-1/Nrf2/NF-κB Signaling Pathway 110 120 10.34172/PS.026.42565 EN Ghasem Khazen https://orcid.org/0009-0003-6183-2492 Fereshteh Farajdokht Saeed Sadigh-Eteghad Mahtab Rajabi-Jourshari Zahra Sheikhalizadeh Ahad Banagozar Mohammadi Mostafa Araj-Khodaei Sahar Khazen Javad Mahmoudi https://orcid.org/0000-0001-9755-9422 Journal Article 10.34172/PS.026.42565 2025 04 26 2025 07 12 Background: Aging is associated with a wide range of cognitive impairments that affect the quality of life in the elderly. This study aimed to assess the neuroprotective properties of the hydro-alcoholic extract of Melissa officinalis L. (HAEMO) on cognitive impairment mediated by the D-galactose/AlCl₃-induced accelerated aging model. Methods: The C57BL/6 mice were allocated into young and aged control groups, and three aged groups received different doses of HAEMO for 60 days. The performance of mice was assessed using the Lashley III maze and the novel object recognition test to assess cognitive function. Hippocampal tissue was examined not only for oxidative stress indicators (TAC, MDA, GPx and SOD) but also used for estimations of Sirt-1, Nrf2, NF-кB, IL-6, and TNF-α proteins. Results: The results indicated improved spatial and recognition memories in the HAEMO-received aged animals. The behavioral advantages were probably linked to diminished lipid peroxidation, increased antioxidant enzyme activities, and enhancement of the hippocampal Sirt-1/Nrf2 pathway. Moreover, the HAEMO regimen reduced inflammatory markers (NF-κB, TNF-α, and IL-6) in the hippocampus. Conclusion: HAEMO exerts a modulatory effect on the hippocampal Sirt-1/Nrf2/NF-κB pathway, offering a neuroprotective approach against progressive oxidative stress and neuroinflammation that develop with aging. Additional research is necessary to completely understand the therapeutic potential of HAEMO in the preservation of cognition during aging.