Rehmannia Extract On Behavior And Brain Degeneration In Aging Mice And Mechanism

Objective: Aging is the degenerative changes in body tissuesand organs functions as the subject grows older. Age-relatedrecession in brain performance is a normal physio-phenomenonof biological aging of the central nervous system post the periodsof growth, development and maturity. The most clinicalmanifestation is the decline in learning and memory ability. D(?) hu(?)ng (Radix Rehmanniae) is the root of Rehmannia glutinosa Libosch,main benefit is for strengthening the Yin and kidney-linked organs.It is used and also as a major ingredient in medicines, foranti-aging. In this experiment, natural aged mice were used toexamine the effects of Rehmannia glutinosa Libosch extracts (RCE)on their behavior, age-related degenerative changes in brain,molecular pathological impacts and to study the biologicalbasics of RGE effect on anti-aging.Methods: Natural aged mice were chosen as the study subject.Aims: To examine and to evaluate the effect of RGE on: (1) learningand memory of aged mice by using Morris water maze, open-field testand passive avoidance test; neuron density in hippocampal CA3 areaof aged mice by means of Hematoxylin-Eosin (HE) dyeing; aged micebrain's dentate gyrus (DG) neurons synthesis and differentiationby 5-bromo-2-deoxyuridine (BrdU) Labeling. (2) brain tissueapoptosis ( AI) by Tdt-mediated dUTP nick end labeling (TUNEL);copper/zinc superoxide dismutase (Cu-ZnSOD), malondialdehyde (MDA)expression level in brain tissue of aged mice by spectrophotometricdetection. (3) fragment length of telomere and the telomeraseactivity of natural aged mice by Southern Blot and telomeric repeat amplification protocol (TRAP). (4) aged mice brain tissue p53,p21^wafl gene expression by methods of real-time PCR, western blot,etc.Results: After feeding with RGE for 30 days, (1) Improvementwas obvious in the age-related behavior of the natural agedmice, increasing memory ability in learning for elderly mice,improving the aging-caused decline in neuron density in thehippocampal CA3 area, increasing the rate of cell synthesis anddifferentiation of brain's DG neurons. (2) Improving rate of AI inbrain tissues of the natural aged mice; significantly increased thecontent of Cu-ZnSOD in brain tissue of the natural aged mice, theincrease was correlatd with RGE concentration, but was not obviousin MDA expression level. (3) Significantly enhancing telomeraseactivity in the brain tissues of the natural aged mice compared withthe elderly control group. Change in the telomere length waspositive in brain tissues of the RGE fed natural aged mice. (4)Inhibited p21^wafl gene transcription in the natural aged mice, mighthad been through the affected gene expression of non-P53 dependentp21^wafl, reducing the content of P21 protein expression.Conclusion: The process of aging and age-related degenerativechanges in the brain is mainly related to factors of genetics,oxidative damage, neuronal apoptosis, immune system abnormalities,hypoxia and ischemia in brain tissues and others. TraditionalChinese Medicine (TCM) regards the age-related neurodegenerativediseases are mostly syndrome of "dullness", "herd", "dementia"and "forgetfulness". Strengthening the functions of Yin andkidney-linked organs is the most important means for Anti-aging.AppliCation of RGE can obviously increase the memory ability of learning in elderly mice, and improve age-related degenerativechanges in the brain. The effectiveness is biologically based onthe possibilities of the increased content of antioxidant Cu-ZnSODin the brain tissue of the natural aged mice, the enhancedtelomerase activity in brain cells, the increased rate of cellsynthesis and differentiation of brain's DG neurons and the reducedoxidative damage caused by DNA destruction during aging. Thenthrough the influence of non-P53 dependent p21^wafl wafl expression,to decrease the cell cycle regulation for the P21core proteinexpression, and improving AI in the brain cells of the natural agedmice and declining the neuron density in hippocampal CA3 area causedby aging. Hence, the memory ability in learning is increased inelderly mice and the age-related changes in behavior of the naturalaged mice are improved.