Total alkaloids from the seed embryo of Nelumbo nucifera Gaertn. improve cognitive impairment in APP/PS1 mice and protect Aβ-damaged PC12 cells

ABSTRACT

The seed embryo of Nelumbo nucifera Gaertn. is a famous traditional Chinese medicine and food which is considered conducive to the prevention of Alzheimer's disease (AD). In this study, the effect and mechanism of TASENN (total alkaloids from the seed embryo of Nelumbo nucifera Gaertn.) on AD mice and amyloid-β (Aβ) injured PC12 cells were evaluated. HPLC-UV analysis showed that the extracted TASENN (purity = 95.6%) mainly contains Liensinine, Isoliensinine, and Neferine (purity was 23.01, 28.02, and 44.57%, respectively). In vivo, oral treatment with TASENN (50 mg/kg/day for 28 days) improved the learning and memory functions of APP/PS1 transgenic mice, ameliorated the histopathological changes of cortical and hippocampal neurons, and inhibited neuronal apoptosis. We found that TASENN reduced the phosphorylation of Tau and the formation of neurofibrillary tangles (NFTs) in APP/PS1 mouse brain. Moreover, TASENN down-regulated the expression of APP and BACE1, ameliorated Aβ deposition, and inhibited microglial proliferation and aggregation. The elevated protein expression of CaM and p-CaMKII in APP/PS1 mouse brain was also reduced by TASENN. In vitro, TASENN inhibited the apoptosis of PC12 cells injured by Aβ_25–35 and increased the cell viability. Aβ_25–35-induced increase of cytosolic free Ca²⁺ level and high expression of CaM, p-CaMKII, and p-Tau were decreased by TASENN. Our findings indicate that TASENN has a potential therapeutic effect on AD mice and a protective effect on PC12 cells. The anti-AD activity of TASENN may be closely related to its negative regulation of the CaM pathway.

GRAPHICAL ABSTRACT

KEYWORDS:

• Alkaloids
• Seed embryo of Nelumbo nucifera Gaertn
• APP/PS1 mice
• PC12 cells
• Alzheimer's disease
• ‌Amyloid-β
• Tau phosphorylation
• ‌Microglia
• ‌CaM

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

Supporting data are available from the corresponding author.

Additional information

Funding

This research was supported by the National Natural Science Foundation of China under Grant [number 81503085]; the Natural Science Foundation of Liaoning Province of China under Grant [numbers 20180551168 and 2021-MS-155]; and the Basic Research Foundation of Liaoning Province of China under Grant [number LJC202008].

Notes on contributors

Xue-Lian Meng

Xue-Lian Meng, Ph.D. is a professor in School of Pharmaceutical Science, Liaoning University, Shenyang, China. Her research focus is on the drug screening and mechanism of neurodegenerative diseases (especially Alzheimer’s disease).

Jing-Su Xue

Jing-Su Xue is an M.S. student in School of Pharmaceutical Science, Liaoning University, Shenyang, China, exploring drugs for prevention and treatment of Alzheimer’s disease in vivo.

Shu-Jie Su

Shu-Jie Su is an M.S. student in School of Pharmaceutical Science, Liaoning University, Shenyang, China, exploring drugs for prevention and treatment of Alzheimer’s disease in vivo.

Jiang-Min Gou

Jiang-Min Gou is an M.S. student in School of Pharmaceutical Science, Liaoning University, Shenyang, China, exploring drugs for prevention and treatment of Alzheimer’s disease in vitro.

Jing Lu

Jing Lu, Ph.D. is a professor in School of Pharmaceutical Science, Liaoning University, Shenyang, China. Her research focus is on the extraction and purification of active components of traditional Chinese medicine.

Chang-Lan Chen

Chang-Lan Chen, Ph.D. is a professor in School of Pharmaceutical Science, Liaoning University, Shenyang, China. His research interests are the function of selenoproteins and drugs for Alzheimer’s disease.

Cheng-Bin Xu

Cheng-Bin Xu is a Professor in School of Environmental Science, Liaoning University, Shenyang, China. His research interests are environmental microbiology, environmental toxicology, and pharmacology.