Asiatic acid nullified aluminium toxicity in in vitro model of Alzheimer rsquo s disease

Abstract

Aluminium (Al) is a ubiquitously distributed environmental toxicant that lacks biological functions; however, its accumulation in the brain has been demonstrated to be linked to several neuropathological conditions particularly Alzheimer's disease (AD). Asiatic acid (AA), a triterpene extracted from , has been reported to cross the blood brain barrier and also displayed antioxidant and neuroprotective activities. The present study was aimed to explore the neuroprotective effect of AA against aluminium maltolateAl(mal)) induced neurotoxicity by assessing cell viability, mitochondrial membrane potential, levels of reactive oxygen species (ROS), DNA damage and apoptosis (Hoechst and dual staining, comet assay; expressions of pro-apoptotic, anti-apoptotic and signaling indices) via AKT/GSK-3β signaling pathway in SH-SY 5Y neuroblastoma cells. Pre-treatment with AA significantly enhanced cell viability, attenuated rotenone-induced ROS, mitochondrial membrane dysfunction and apoptosis regulating AKT/GSK-3β signaling pathway. Downregulation of Al induced neurodegeneration may be one of the approaches to control the impairment of metal ion homeostasis leading to neuronal injury in early development of AD. However, more extensive work in animal model is desirable to confirm its neuroprotective action.

Therapeutic Potential of Centella asiatica and Its Triterpenes: A Review

“…More importantly, C. asiatica and its extracts improved neurological diseases by reducing inflammatory factors, balancing oxidative stress, repairing abnormal expression of mitochondrial-related proteins, and improving the content of BDNF. In addition, they reduced related nerve cell apoptosis, increased synaptic density, and improved the survival rate of neural cells (Chaisawang et al, 2017;Gray et al, 2018a;Rather et al, 2018b).…”

Pharmacological Properties, Molecular Mechanisms, and Pharmaceutical Development of Asiatic Acid: A Pentacyclic Triterpenoid of Therapeutic Promise

“…Aluminum is a widely distributed environmental toxicant that upon accumulation in the brain shows associated with neurodegenerative diseases, especially AD. Recently, AA has showed neuroprotective against aluminum maltolate-induced neurotoxicity (Ahmad Rather et al, 2018 ). AA found to enhance cell viability, ameliorate mitochondrial membrane dysfunction, and resultant oxidative stress and apoptosis-regulating AKT/GSK-3β signaling pathway in neuroblastoma cells (SH-SY5Y).…”

“…AA mitigated rise in aluminum, activity of acetylcholinesterase and gamma secretases along with amyloid β 1−42 , glial fibrillary acidic protein and ionized calcium binding adaptor molecule-1. AA also reduced inflammatory mediators iNOS, COX-2, and NF-κB in the hippocampus and cortex (Ahmad Rather et al, 2018 ).…”

Asiatic Acid Protects Dopaminergic Neurons from Neuroinflammation by Suppressing Mitochondrial ROS Production

“…AA derivatives have been shown to counteract glutamate-induced excitotoxicity in nerve cells (Lee et al ., 2000), while asiaticoside derivatives can antagonize β-amyloid-induced nerve damage (Jew et al ., 2010; Mook-Jung et al ., 2015). Furthermore, AA shows neuroprotective effects against aluminum-induced neuronal toxicity in vivo and in vitro (Ahmad et al ., 2018a, 2018b). Xiong has shown that rotenone or H 2 O 2 can reduce the mitochondrial membrane potential (MMP) of SH-SY5Y DA cells.…”