[Effect and mechanism of Epimedium flavanoids for aging retardation from viewpoint of transcriptomics and metabonomics].
OBJECTIVE
To investigate the effect and its mechanism of Epimedium flavanoids (EF) in retarding aging with different systematic viewpoints.


METHODS
Hypothalamus, pituitary, adrenal and lymphocytes taken from 4-, 10-, 18-, 24-month old rats and from EF treated 24-month old rats were used to measure whole genome mRNA expression by gene array. Serum samples were used for metabonomic assay with high performance liquid chromatography. Using specific gene chip for NF-kappaB signaling pathway to detect the gene expression of the molecule related to that pathway in lymphocytes. Then, a neural network (NN) model was established upon the data obtained to quantitatively evaluate the degree of aging and the efficacy of drug intervention.


RESULTS
Gene expression of 199 genes showedan age-dependent pattern, most of which were reversed by EF, and the output of NN model showed that EF made the transcriptomics of 24-month old rats to 8-13 months. Seventeen metabolites among the 1,885 peaks detected were identified to have significant age-depending changes, and EF intervention reset the level of metabolites to a younger (18-month) level. The integral level of gene expression for NF-kappaB signaling pathway decreased significantly along with the increasing of age, and was significantly elevated by EF, NN model showed it approached to 10.5-month old.


CONCLUSIONS
Phenotype of aging at different levels demonstrates a common age-dependent trend; EF can reverse this age-dependent change at different levels in a synchronous manner.
Huang
Jian-Hua
JH
Institute of Integrative Medicine, Huashan Hospital Affiliated to Fudan University, Shanghai.
Shen
Zi-Yin
ZY
Wu
Bin
B
D000311:Adrenal Glands / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D000375:Aging / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D034181:Epimedium / Q000737:chemistry*; D005419:Flavonoids / Q000494:pharmacology*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D007031:Hypothalamus / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000097:blood / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010902:Pituitary Gland / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects
D005419:Flavonoids; D016328:NF-kappa B