Combining antioxidant astaxantin and cholinesterase inhibitor huperzine A boosts neuroprotection

Yang,Xin; Wei,Han‑Mei; Hu,Guo‑Yan; Zhao,Jun; Long,Li‑Na; Li,Chang‑Jian; Zhao,Zi‑Jun; Zeng,He‑Kun; Nie,Hong

doi:10.3892/mmr.2020.10920

Combining antioxidant astaxantin and cholinesterase inhibitor huperzine A boosts neuroprotection

Authors:
- Xin Yang
- Han‑Mei Wei
- Guo‑Yan Hu
- Jun Zhao
- Li‑Na Long
- Chang‑Jian Li
- Zi‑Jun Zhao
- He‑Kun Zeng
- Hong Nie
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Affiliations: Department of Pharmacy, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510700, P.R. China, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou, Guangdong 510632, P.R. China, Department of Clinical Laboratory, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510700, P.R. China, Department of Obstetrics, Guangdong Women and Children Hospital, Guangzhou, Guangdong 510010, P.R. China
Published online on: January 9, 2020 https://doi.org/10.3892/mmr.2020.10920
Pages: 1043-1050
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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, Aβ25‑35, 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 Aβ25‑35. 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.

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