The potential anti-Alzheimer's activity of Oxalis corniculata Linn. Methanolic extract in experimental rats: Role of APOE4/LRP1, TLR4/NF-κβ/NLRP3, Wnt 3/β-catenin/GSK-3β, autophagy and apoptotic cues

Abstract

Ethnopharmacological relevance: Oxalis corniculata (O. corniculata) is a member of Oxalidaceae family, widely distributed in Asia, Europe, America, and Africa, used extensively as food and its traditional folkloric uses include management of epilepsy, gastric disorders, and neurodegenerative diseases, together with its use in enhancing health. Numerous pharmacological benefits of O. corniculata are linked to its anti-inflammatory and antioxidant abilities. One of the most prevalent neurodegenerative disorders is Alzheimer's disease (AD) in which neuroinflammation and oxidative stress are its main pathogenic processes.

Aim of the study: Our research aimed to study the neuroprotective effect of the methanolic extract of Oxalis corniculata Linn. (O. corniculata ME), compared to selenium (Se) against AlCl₃-induced AD.

Materials and methods: Forty male albino rats were allocated into four groups (Gps). Gp I a control group, the rest of the animals received AlCl₃ (Gp II-Gp IV). Rats in Gp III and IV were treated with Se and O. corniculata ME, respectively.

Results: The chemical profile of O. corniculata ME was studied using ultraperformance liquid chromatography-electrospray ionization-quadrupole time-of-flight mass spectrometry, allowing the tentative identification of sixty-six compounds, including organic acids, phenolics and others, cinnamic acid and its derivatives, fatty acids, and flavonoids. AlCl₃ showed deterioration in short-term memory and brain histological pictures. Our findings showed that O. corniculata ME and selenium helped to combat oxidative stress produced by accumulation of AlCl₃ in the brain and in prophylaxis against AD. Thus, Selenium (Se) and O. corniculata ME restored antioxidant defense, via enhancing Nrf2/HO-1 hub, hampered neuroinflammation, via TLR4/NF-κβ/NLRP3, along with dampening apoptosis, Aβ generation, tau hyperphosphorylation, BACE1, ApoE4 and LRP1 levels. Treatments also promoted autophagy and modulated Wnt 3/β-catenin/GSK3β cue.

Conclusions: It was noted that O. corniculata ME showed a notable ameliorative effect compared to Se on Nrf2/HO-1, TLR4/NF-κβ/NLRP3, APOE4/LRP1, Wnt 3/β-catenin/GSK-3β and PERK axes.

Keywords: APOE4/LRP1; Alzheimer's disease; Autophagy; Oxalis corniculata Linn; Oxidative stress; PERK/CHOP/Bcl-2; TLR4/NF-κβ/NLRP3; Wnt 3/β-catenin/GSK-3β.