Menthol inhibits amyloid-β protein polymerization to protect neurocytes

Wang Jing; Wang Ting; Han Zhitao; Liu Zhian

doi:10.3760/cma.j.issn.1673-4777.2018.02.017

Abstract：Objective To determine whether menthol can inhibit amyloid-β protein(Aβ) polymerization to protect neurocytes.Methods The docking construction between menthol and Aβ was structured by computer modeling technique.The combination between menthol and Aβ was observed by transmission electron microscope using 30 μmol/L Aβ co-cultivating with 200 μmol/L menthol for 72 h;30 μmol/L Aβ polymerized alone and cultivated with 10％ dimethyl sulfoxide were set as control.Human neuroblastoma cell line SH-SY5Y was co-cultivated with 30 μmol/L Aβ or 30 μmol/L Aβ ± 200 μmol/L menthol,and cell proliferation was tested after 12,24,36,72 h by Cell Counting Kit-8 (CCK8).Twenty 6 months old Aβ precursor protein(APP)/presenilin-1 (PS1) transgenic mice were randomly divided into experimental group(n =10) treated by 1 mg/g menthol lavage and control group(n =10) treated by 0.9％ sodium chloride injection lavage till the mice were 10 months old;the formation of senile plaques in hippocampus was tested by immunohistochemistry.Results Computer modeling showed 2 stable docking positions between menthol and Aβ.Transmission electron microscopy showed that Aβ polymerization could be significantly depressed by menthol co-cultivation.CCK8 test showed that menthol could inhibit the neurotoxicity induced by Aβ;the activity of SH-SY5Y cells had significant differences between Aβ group and Aβ ± menthol group[12 h:(0.85 ±0.12) vs (1.13 ±0.14),P ＜0.05;24 h:(0.77 ±0.09) vs (1.09 ±0.11),P ＜0.05;36h:(0.67±0.13) vs (1.01 ±0.11),P＜0.05;72 h:(0.49 ±0.07) vs (0.92±0.10),P＜0.01].Immunohistochemistry test showed that menthol could reduce senile plaque formation in hippocampus of mice.Conclusion Menthol can inhibit Aβ monomer translating to oligomer to prevent nerve cell injury.