Abstract
Background: Physalin B (PB) is one of the main active compounds of Solanaceae plants, with a wide range of biological activities. PB reportedly has the potential to treat Alzheimer’s disease (AD).
Objective: In this study, we investigated the effect of PB on Tau phosphorylation and cell apoptosis using Tau-expressing HEK293 cells (HEK293/Tau) as a cellular model.
Methods: The optimum concentration of PB to treat HEK293/Tau cells was determined using the CCK-8 assay. Additionally, the expression of FoxO1, Tau-5, p-Tau (T231, S262, and S404), ERK, p-ERK, GSK-3β, and p-GSK-3β was detected using western blotting to determine the effect of PB on Tau phosphorylation. The apoptosis rate was detected using flow cytometry, and the expression of Bax and Bcl-2 was detected using western blotting and verified using real-time quantitative polymerase chain reaction (RT-qPCR). Moreover, cells were transfected with FoxO1 siRNA to downregulate FoxO1 expression, and the expression of the above-mentioned proteins was detected to verify the effect of PB on Tau phosphorylation and cell apoptosis.
Results: After 24 h of PB treatment, the phosphorylation levels of Tau at S404, S262, and T231 sites decreased significantly, and the activities of GSK-3β and ERK were inhibited. PB also reduced cell apoptosis by reducing the expression of Bax and increasing the expression of Bcl-2. In addition, PB decreased Tau phosphorylation and cell apoptosis by upregulating FoxO1.
Conclusion: The natural compound PB exhibited a protective effect in the AD cell model by increasing FoxO1 expression and reducing Tau phosphorylation and cell apoptosis.
Keywords: Physalin B, Tau phosphorylation, Apoptosis, FoxO1, Alzheimer’s disease, AD cell model.
[http://dx.doi.org/10.1002/jnr.23011] [PMID: 22344941]
[http://dx.doi.org/10.1016/j.jalz.2016.01.004] [PMID: 26900132]
[http://dx.doi.org/10.3390/molecules25245789] [PMID: 33302541]
[http://dx.doi.org/10.1016/j.neuropharm.2009.07.021] [PMID: 19628001]
[http://dx.doi.org/10.1007/s00401-022-02419-2] [PMID: 35412102]
[http://dx.doi.org/10.1073/pnas.72.5.1858] [PMID: 1057175]
[http://dx.doi.org/10.1016/j.pneurobio.2018.12.005]
[http://dx.doi.org/10.3389/fnagi.2019.00204]
[http://dx.doi.org/10.1172/JCI23126] [PMID: 16100571]
[http://dx.doi.org/10.1016/j.immuni.2012.01.015] [PMID: 22425248]
[http://dx.doi.org/10.1155/2022/7619255] [PMID: 35154571]
[http://dx.doi.org/10.18632/aging.102171] [PMID: 31467256]
[http://dx.doi.org/10.3389/fnagi.2022.902092] [PMID: 36081896]
[http://dx.doi.org/10.17179/excli2016-852] [PMID: 28507478]
[http://dx.doi.org/10.1016/j.neurobiolaging.2013.07.019] [PMID: 23973442]
[http://dx.doi.org/10.1016/j.neuroscience.2019.08.010] [PMID: 31404586]
[http://dx.doi.org/10.1016/j.neulet.2020.135322] [PMID: 32860886]
[http://dx.doi.org/10.4103/1673-5374.205108] [PMID: 28553349]
[http://dx.doi.org/10.1016/j.phytochem.2021.112925] [PMID: 34487922]
[http://dx.doi.org/10.1016/j.fitote.2016.05.010] [PMID: 27215128]
[http://dx.doi.org/10.1016/j.jep.2020.112956] [PMID: 32442587]
[http://dx.doi.org/10.1016/j.jinsphys.2012.10.001] [PMID: 23085484]
[http://dx.doi.org/10.1021/np200260f] [PMID: 21954931]
[http://dx.doi.org/10.1111/bph.15588] [PMID: 34409595]
[http://dx.doi.org/10.1016/S1875-5364(21)60090-0] [PMID: 34688463]
[http://dx.doi.org/10.1002/jcp.28988] [PMID: 31385301]
[http://dx.doi.org/10.1142/S0192415X20500251] [PMID: 32329645]
[http://dx.doi.org/10.1007/s00401-018-1855-6] [PMID: 29752551]
[http://dx.doi.org/10.1016/j.conb.2021.03.003]
[http://dx.doi.org/10.2174/1568026620666200106125910] [PMID: 31903881]
[http://dx.doi.org/10.1016/j.bbi.2018.04.014]
[http://dx.doi.org/10.1007/s11064-021-03273-6] [PMID: 33710538]
[http://dx.doi.org/10.1021/acschemneuro.0c00617] [PMID: 33320518]
[http://dx.doi.org/10.1007/s12035-022-02918-z] [PMID: 35701718]
[http://dx.doi.org/10.3233/JAD-160912] [PMID: 27716675]
[http://dx.doi.org/10.1042/EBC20210030] [PMID: 34897457]
[http://dx.doi.org/10.1039/C9FO02133G] [PMID: 31793596]
[http://dx.doi.org/10.1007/s00204-014-1448-7] [PMID: 25618543]
[http://dx.doi.org/10.1038/sj.emboj.7601126] [PMID: 16642033]
[PMID: 34765288]
[http://dx.doi.org/10.2147/CIA.S64758]
[http://dx.doi.org/10.1016/j.neuro.2013.12.012] [PMID: 24406377]
[http://dx.doi.org/10.1155/2015/569392] [PMID: 26171319]
[http://dx.doi.org/10.1016/bs.ctdb.2017.10.002] [PMID: 29433734]
![Wayfinder Image](/images/wayfinder.jpg)