Acute,Subacute Toxicology Evaluation And Mechanisms Study On Delaying Aging Of Polysaccharides From Angelica And Astragalus

Polysaccharides from angelica and astragalus(AAP) were extracted from angelica and astragalus, which were mixed in a ratio of 1 ∶ 5(w/w) according to ancient hematinic decoction-Danggui Buxue Decoction. The composition and structure of AAP had been made in our previous work. And AAP shown better delaying senescence in oue preliminary research. However, the anti-senescence related mechanisms in vivo of AAP has little been reported in the references of inland and foreign in this aspect, and the safety evaluation has not been reported.In this study, the AAP was extracted from a mixture of angelica sinensis and astragalus membranaceus roots by an enzyme-assisted extraction and deproteinization technique based on the previous researches result. The content of AAP was determined through the phenol-sulfuric acid method, using glucose as standard, and to evaluate its safety by observing the acute toxic reaction of mice and subacute toxicity to rats. In order to probe the mechanisms of AAP in delaying senescence, aging model rats were established by injecting D-galactose subcutaneously, the Vit E was used as positive medicine to study the effect of AAP on aging rat vital organs.AAP were extracted by an enzyme-assisted and deproteinization technique, and sugar contents was determined to be 82.82%. The primary safety of AAP was evaluated by observing the acute toxic reaction of mice and subacute toxicity to rats.Acute toxicity test proved that the MTD of AAP was more than 15g/kg, the results suggested that AAP was nontoxic material. The results of subacute toxicity test shown that the increases of bodyweight, organ coefficient and biood biochemical indexes have no significant difference as compared with the normal control rats, which inplied the AAP was higher safe agent.The effect of AAP on brain showed that MDH, SDH and SOD activities significantly were increased, MAO active and MDA level were reduced. At the same time, we found that telomerase activity was raised, p16 protein expression was decreased. AAP has repair effect on the brain of D-galactose-induced aging rats from the multiple points of view.The effect of AAP on heart showed that AAP could decrease the mt DNA content. The significant difference was found between AAP group and D-gal model group(p < 0.05), and AAP in low-dose group has significant difference as comparedwith the positive control group(p < 0.01). The mt DNA deletion fragment was found in each group, which was approximately 5 kb. We performed the histological analyses obtained from heart tissues, the neatly arranged myocardial cells, clear cell nucleus and dispersed chromatin were observed from the AAP group. The results demonstrated that AAP had obvious effect on protecting the heart functions in D-galactose-induced aging rats.The effert of AAP on serum implied that the contents of GLU, TG, TC, GSP and AGES were decreased, AAP could effective to inhibit the nonenzymatic reactions of glycosylation and protect the angiocarpy of aging rats.The results indicated that AAP could enhance SOD, GSH-PX activities, GSH content and decrease AGES, PC, MDA levels in kidney of D-galactose-induced aging rats, which reduced the carbonyl damage and played the action of postponing senility in kidney.