Green Tea Seed Isolated Theasaponin E1 Ameliorates AD Promoting Neurotoxic Pathogenesis by Attenuating Aβ Peptide Levels in SweAPP N2a Cells
Alzheimer’s disease (AD) is the most frequent type of dementia affecting memory, thinking and behaviour. The major hallmark of the disease is pathological neurodegeneration due to abnormal aggregation of Amyloid beta (Aβ) peptides generated by β- and γ-secretases via amyloidogenic pathway. Purpose o...
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MDPI AG
2020-05-01
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| Series: | Molecules |
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| author | Muhammad Imran Khan Jin Hyuk Shin Min Yong Kim Tai Sun Shin Jong Deog Kim |
| author_facet | Muhammad Imran Khan Jin Hyuk Shin Min Yong Kim Tai Sun Shin Jong Deog Kim |
| author_sort | Muhammad Imran Khan |
| collection | DOAJ |
| description | Alzheimer’s disease (AD) is the most frequent type of dementia affecting memory, thinking and behaviour. The major hallmark of the disease is pathological neurodegeneration due to abnormal aggregation of Amyloid beta (Aβ) peptides generated by β- and γ-secretases via amyloidogenic pathway. Purpose of the current study was to evaluate the effects of theasaponin E1 on the inhibition of Aβ producing β-, γ-secretases (BACE1, PS1 and NCT) and acetylcholinesterase and activation of the non-amyloidogenic APP processing α-secretase (ADAM10). Additionally, theasaponin E1 effects on Aβ degrading and clearing proteins neprilysin and insulin degrading enzyme (IDE). The effect of theasaponin E1 on these crucial enzymes was investigated by RT-PCR, ELISA, western blotting and fluorometric assays using mouse neuroblastoma cells (SweAPP N2a). theasaponin E1 was extracted and purified from green tea seed extract via HPLC, and N2a cells were treated with different concentrations for 24 h. Gene and protein expression in the cells were measured to determine the effects of activation and/or inhibition of theasaponin E1 on β- and γ-secretases, neprilysin and IDE. Results demonstrated that theasaponin E1 significantly reduced Aβ concentration by activation of the α-secretase and neprilysin. The activities of β- and γ-secretase were reduced in a dose-dependent manner due to downregulation of <i>BACE1</i>, presenilin, and nicastrin. Similarly, theasaponin E1 significantly reduced the activity of acetylcholinesterase. Overall, from the results it is concluded that green tea seed extracted saponin E1 possess therapeutic significance as a neuroprotective natural product recommended for the treatment of Alzheimer’s disease. |
| first_indexed | 2024-03-10T19:46:33Z |
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| spelling | doaj.art-53752657a17a450198d7bb050d7eb7ea2023-11-20T00:43:31ZengMDPI AGMolecules1420-30492020-05-012510233410.3390/molecules25102334Green Tea Seed Isolated Theasaponin E1 Ameliorates AD Promoting Neurotoxic Pathogenesis by Attenuating Aβ Peptide Levels in SweAPP N2a CellsMuhammad Imran Khan0Jin Hyuk Shin1Min Yong Kim2Tai Sun Shin3Jong Deog Kim4Department of Biotechnology, Chonnam National University, San96-1, Dun-Duk Dong, Yeosu, Chonnam 550-749, KoreaDepartment of Biotechnology, Chonnam National University, San96-1, Dun-Duk Dong, Yeosu, Chonnam 550-749, KoreaDepartment of Refrigeration Engineering, Chonnam Natational University, San96-1, Dun-Duk Dong, Yeosu, Chonnam 550-749, KoreaResearch center on Anti-Obesity and Health Care, Chonnam National University, San96-1, Dun-Duk Dong, Yosu, Chonnam 550-749, KoreaDepartment of Biotechnology, Chonnam National University, San96-1, Dun-Duk Dong, Yeosu, Chonnam 550-749, KoreaAlzheimer’s disease (AD) is the most frequent type of dementia affecting memory, thinking and behaviour. The major hallmark of the disease is pathological neurodegeneration due to abnormal aggregation of Amyloid beta (Aβ) peptides generated by β- and γ-secretases via amyloidogenic pathway. Purpose of the current study was to evaluate the effects of theasaponin E1 on the inhibition of Aβ producing β-, γ-secretases (BACE1, PS1 and NCT) and acetylcholinesterase and activation of the non-amyloidogenic APP processing α-secretase (ADAM10). Additionally, theasaponin E1 effects on Aβ degrading and clearing proteins neprilysin and insulin degrading enzyme (IDE). The effect of theasaponin E1 on these crucial enzymes was investigated by RT-PCR, ELISA, western blotting and fluorometric assays using mouse neuroblastoma cells (SweAPP N2a). theasaponin E1 was extracted and purified from green tea seed extract via HPLC, and N2a cells were treated with different concentrations for 24 h. Gene and protein expression in the cells were measured to determine the effects of activation and/or inhibition of theasaponin E1 on β- and γ-secretases, neprilysin and IDE. Results demonstrated that theasaponin E1 significantly reduced Aβ concentration by activation of the α-secretase and neprilysin. The activities of β- and γ-secretase were reduced in a dose-dependent manner due to downregulation of <i>BACE1</i>, presenilin, and nicastrin. Similarly, theasaponin E1 significantly reduced the activity of acetylcholinesterase. Overall, from the results it is concluded that green tea seed extracted saponin E1 possess therapeutic significance as a neuroprotective natural product recommended for the treatment of Alzheimer’s disease.https://www.mdpi.com/1420-3049/25/10/2334Alzheimer’s diseaseamyloid precursor proteinsamyloidogenic pathwayα-secretaseSweAPP N2a cellstheasaponin E1 |
| spellingShingle | Muhammad Imran Khan Jin Hyuk Shin Min Yong Kim Tai Sun Shin Jong Deog Kim Green Tea Seed Isolated Theasaponin E1 Ameliorates AD Promoting Neurotoxic Pathogenesis by Attenuating Aβ Peptide Levels in SweAPP N2a Cells Molecules Alzheimer’s disease amyloid precursor proteins amyloidogenic pathway α-secretase SweAPP N2a cells theasaponin E1 |
| title | Green Tea Seed Isolated Theasaponin E1 Ameliorates AD Promoting Neurotoxic Pathogenesis by Attenuating Aβ Peptide Levels in SweAPP N2a Cells |
| title_full | Green Tea Seed Isolated Theasaponin E1 Ameliorates AD Promoting Neurotoxic Pathogenesis by Attenuating Aβ Peptide Levels in SweAPP N2a Cells |
| title_fullStr | Green Tea Seed Isolated Theasaponin E1 Ameliorates AD Promoting Neurotoxic Pathogenesis by Attenuating Aβ Peptide Levels in SweAPP N2a Cells |
| title_full_unstemmed | Green Tea Seed Isolated Theasaponin E1 Ameliorates AD Promoting Neurotoxic Pathogenesis by Attenuating Aβ Peptide Levels in SweAPP N2a Cells |
| title_short | Green Tea Seed Isolated Theasaponin E1 Ameliorates AD Promoting Neurotoxic Pathogenesis by Attenuating Aβ Peptide Levels in SweAPP N2a Cells |
| title_sort | green tea seed isolated theasaponin e1 ameliorates ad promoting neurotoxic pathogenesis by attenuating aβ peptide levels in sweapp n2a cells |
| topic | Alzheimer’s disease amyloid precursor proteins amyloidogenic pathway α-secretase SweAPP N2a cells theasaponin E1 |
| url | https://www.mdpi.com/1420-3049/25/10/2334 |
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