Neuroprotective effects of Chlorella vulgaris loaded niosomes via SIRT1 activation in aluminum chloride-induced Alzheimer’s model

TL;DR

This study shows that Chlorella vulgaris, delivered via niosomes, protects against aluminum-induced Alzheimer's-like damage in rats by activating a key brain protein pathway.

Contribution

The novel contribution is demonstrating the neuroprotective efficacy of Chlorella vulgaris-loaded niosomes in an aluminum-induced Alzheimer’s model via SIRT1/miRNA-134/GSK3β modulation.

Findings

CV-loaded niosomes improved oxidative stress, behavioral deficits, and neurotransmitter dysfunction in AlCl3-exposed rats.

CV formulations activated SIRT1, downregulated miRNA-134, and increased BDNF expression, enhancing neuronal survival.

CV reduced Tau hyperphosphorylation, Aβ accumulation, neuroinflammation, and apoptosis in the rat model.

Abstract

Aluminum exposure is linked to the development of many neurodegenerative disorders including Alzheimer’s disease (AD), by disrupting molecular and cellular homeostasis in the brain. Chlorella vulgaris (CV), a green microalga, is reported to have antioxidant, anti-inflammatory, and neuroprotective properties. However, their role on Aluminum chloride (AlCl3)-induced AD and amyloid β (Aβ) clearance has not yet been fully elucidated. This research aimed to investigate the protective effectiveness of CV-loaded niosome (CV-LN) as a drug delivery system, in comparison to free form, against AlCl3-induced Alzheimer’s-like neurodegeneration in rats with special emphasis on SIRT1/miRNA-134/GSK3β axis. A niosomal formulation of Span 60, and cholesterol was chosen as an optimum formulation. Administration of CV or CV-LN dramatically improves the impaired oxidative markers, behavioral deficits, cholinergic and serotonergic dysfunctions, by significantly inhibiting monoamine oxidase, acetylcholinesterase activities and increasing serotonin level in brain of AlCl3-exposed rats. In parallel, CV or CV-LN triggers the activation of Sirtuin-1 (SIRT1) which downregulates miRNA-134, leading to increased brain-derived neurotrophic factor (BDNF) expression and improved neuronal survival and synaptic plasticity. Furthermore, CV or CV-LN decreases glycogen synthase kinase 3 beta (GSK3β)-mediated Tau hyperphosphorylation associated with clearance of Aβ. Additionally, CV or CV-LN significantly inhibits neuroinflammation by decreasing glial fibrillary acidic protein (GFAP), and apoptosis via modulating BAX, Caspase-3 and BCL2. Histopathological evaluations also supported the above findings. CV-LN formulations exhibited greater neuroprotective efficacy in a rat model, possibly due to better brain delivery and bioavailability. Eventually, CV and particularly CV-LN may hold promise as potential therapeutic candidates for further investigation in the context of neurodegenerative disorders and AD, possibly through modulation of SIRT1/miRNA-134/GSK3β axis.

The online version contains supplementary material available at 10.1038/s41598-025-25892-7.

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