The Role And Preliminary Mechanism Of Ginsenoside Monomers G75 In Anti-aging

Senescence is the general aging state of the individual cells.Cellular senescence refers to the irreversible cell cycle arrest of the cells.Senescent cells undergo changes in morphology,physiology,biochemistry and gene expression.With the deepening of research,it’s well accepted that cell aging is closely related to various life activities.Among the traditional Chinese medicines,ginseng is mainly used to improve human health.Studies in recent years have found that ginsenoside(the active ingredient of ginseng)has diverse biological activities and pharmacological effects including antiaging.However,the anti-aging effect and mechanism of ginsenosides are not yet clear.There are multiple markers of cellular senescence,which behave differently in different senescence models.Our previous work found that histone H4 was degraded before the senescent marker Cyclin A in a variety of cellular senescence models,indicating that the changes in histone H4 level could be used as an indicator for rapid screening of anti-aging drugs.In the present thesis,I established a model of cellular senescence induced by hydrogen peroxide with histone H4 as the target,and I determined that the optimal concentration of hydrogen peroxide treatment was 150 μM and the optimal time was 24 h.Using this model,I screened a variety of ginsenoside monomers.I obtained a new ginsenoside monomer G75 which can restore H4 protein level and determined that the optimal concentration of G75 was 20 μM.Cell-level experiments indicated that G75 had a good anti-senescence effect,which was manifested in its ability to restore the level of hydrogen peroxide-induced cell senescence-related marker Cyclin A,to reduce the expression of p16,p21 and agingrelated β-Gal positive staining ratio,and to restore the hydrogen peroxide-induced G2 phase cell cycle arrest.Through animal experiments including water maze,T maze,and new position recognition,I found that monomer G75 could effectively improve the learning and memory ability of Alzheimer’s disease mice.From cell to animal experiments,I found that monomer G75 had a better anti-aging effect than monomer Rb1.Further,I found that G75 might play an anti-cell senescence role through JNK /p38,AKT signaling pathway.Our research confirmed that histone H4 level could be used as a new indicator for rapid screening of anti-aging drugs.At the same time,I discovered a new anti-aging ginsenoside monomer G75,which provided new precursor compound for anti-aging products or drugs.