# 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.

## Key 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.