Combining antioxidant astaxantin and cholinesterase inhibitor huperzine A boosts neuroprotection

Abstract

oxidative stress is a pathophysiological condition resulting in neurotoxicity, which is possibly associated with neurodegenerative disorders. in this study, the antioxidative effects of the antioxidant astaxanthin (aXT) in combination with huperzine a (Hupa), which is used as a cholinesterase inhibitor for the treatment of alzheimer's disease, were investigated. Pc12 cells were treated with either tert-butyl hydroperoxide (TBHP), or with the toxic version of β-amyloid, aβ 25-35 , to induce oxidative stress and neurotoxicity. cell viability, morphology, lactate dehydrogenase (ldH) release, intracellular accumulation of reactive oxygen species (roS), superoxide dismutase (Sod) activity and malondialdehyde (Mda) content were determined, while neuroprotection was also monitored using an MTT assay. it was found that combining AXT with HupA significantly increased the viability of PC12 cells, prevented membrane damage (as measured by ldH release), attenuated intracellular roS formation, increased Sod activity and decreased the level of Mda after TBHP exposure when compared to these drugs administered alone. Pretreatment with Hupa and aXT decreased toxic damage produced by aβ 25-35. These data indicated that combining an antioxidant with a cholinesterase inhibitor increases the degree of neuroprotection; with future investigation this could be a potential therapy used to decrease neurotoxicity in the brain.

Huperzine A and Its Neuroprotective Molecular Signaling in Alzheimer’s Disease

“…HupA inhibits the cytoplasmic translocation of CytoC and caspase-3 cleavage [69], attenuating apoptotic-inducing signals (see Table 2), and possibly prevents APP-induced mitochondrial dysfunction by reversing the disruption of NIPSNAP1 protein localization in the mitochondrial matrix [37]. HupA also upregulates glutathione peroxidase (GSH-PX), superoxide dismutase (SOD), and catalase (CAT), thus preventing oxidative stress [70]. HupA mediated neuroprotection possibly involves restoration of an intact double membrane, which restores the membrane potential and ATP production, meaning preserved energy homeostasis [35,52] (see Table 2).…”

The protective effect of Astaxanthin on scopolamine - induced Alzheimer’s model in mice

“…This result is in agreement with a previous in vitro study. 22 Additionally, the results of the current research showed that AST demonstrated potent antiinflammatory properties. It inhibited the development of pro-inflammatory mediators such as TNF-α and IL-6, which were increased by scopolamine injection.…”

Huperzine a Extraction From Huperzia Serrata and Its Mechanism of Treating Alzheimer's Disease: A Review

“…Additionally, HupA activates the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-PX), avoiding oxidative stress. (35). The reconstruction of an intact double membrane, which restores the membrane potential and ATP generation, implying preserved energy balance, may play a role in HupAmediated neuroprotection.…”