Research On Aging Effects And Mechanism Of Anti-Bai Araloside

Aging is a normal biological phenomenon that happens inevitably in the process of life. With the development of aging, more and more dyfunctions and disorders take place in the physiological processes of the body, which is the basis of numerous aging-related diseases. Even aging is inevitable, effective drugs and methods can delay the occurrence of aging.In recent years, the number of the aging people (>65years old) has increased dramatically. Study on the mechanism of aging and effective anti-aging drugs becoming more urgent.Aralia taibaiensis belongs to the Aralia chinensis L. Its stem, stem bark, root, root bark, and leave are often used in medicinal drugs. The main ingredients of Aralia taibaiensis include saponin, volatile oil and some trace elements. In our previous study, we found that saponin from Aralia taibaiensis had excellent antioxidative effect. Antioxidation is widely recognized as an effective way of anti-aging. So we hypothesize that saponin from Aralia taibaiensis is likely to have a good anti-aging effect. The main purpose of this research is to explore the anti-aging effect of saponin from Aralia taibaiensis, as well as its mechanism of anti-aging.Methods:In the present study, rats injected with D-galactose (150mg/kg·d)was employed as the aging rat model. Saponin from Aralia taibaiensis (200mg/kg-d) was used for the protective drug. We observed the changes of the coefficients of spleen and thymus, the level of advanced glycosylation end products (AGEs), the activity of β-galactosidase, the contents of Malondialdehyde (MDA), Hydrogen peroxide (H2O2), as well as antioxidant enzyme activity, such as superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), reduced glutathione (GSH). The protein levels of FOXO3a/p-FOXO3a, Akt/p-Akt, p38/p-p38, Erkl/2/p-Erkl/2, JNK/p-JNK, Nrf2/p-Nrf2, HO-1, GCLC, GCLM, SOD1, SOD2, CAT were determinated by Western Blot.Results:(1) After the rats were injected with D-gal for ten weeks, the basic state of the rats became very bad. The coefficients of spleen and thymus of rats in aging model group decreased significantly compared with those in the control group (P<0.05), while supplement of saponin from Aralia taibaiensis remarkbly inhibited the coefficients of spleen and thymus changes in the aging rats (P<0.05).(2) The level of AGEs in aging model group increased significantly compared with that in control group (P<0.05), while supplement of saponin from Aralia taibaiensis effectively inhibited the increased AGEs level in the aging rats (P<0.05).(3) The β-galactosidase activity of rat liver in aging model group was significantly higher than that in the control group, while supplement of saponin from Aralia taibaiensis remarkably inhibited the enhanced β-galactosidase activity in the aging rats.(4) The MDA and H2O2levels in aging model group were much higher than those in the control group (P<0.05), while supplement of saponin from Aralia taibaiensis effectively inhibited the increased levels of MDA and H2O2in the aging rats (P<0.05).(5) The activities of antioxidants including SOD, CAT, GSH and GR in aging model group were significantly lower than those in the control group (P<0.05), while supplement of saponin from Aralia taibaiensis effectively antagonized the reductionof these antioxidant activities in the aging rats (P<0.05).(6) The phosphorylation levels of FOXO3a, Akt, p38, Erkl/2, JNK in aging model group increased significantly (P<0.05), with the down-regulations of Nrf2, p-Nrf2, HO-1, GCLC, GCLM, SOD2and CAT (P<0.05). Supplement of saponin from Aralia taibaiensis remarkebly inhibited the phosphorylation of FOXO3a, Akt, p38, Erkl/2, JNK in the aging model group (P<0.05), with the up-regulations of Nrf2, p-Nrf2, HO-1, GCLC, GCLM, SOD2and CAT (P<0.05).Conclusions:1. D-gal is able to induce aging in rats, on which saponin from Aralia taibaiensis shows excellent anti-aging effect.2. D-gal injection induces the production of reactive oxygen species (ROS), decreases the capacity of anti-oxidation, and causes oxidative stress in rats. The saponin from Aralia taibaiensis can significantly increase the activities of SOD, CAT, GR and the content of GSH, reduce the levels of H2O2, MDA, and AGEs in the aging rats, thus achieve its biology function of anti-aging.3. The saponin from Aralia taibaiensis acts on the Akt/FOXO3a pathway. It inhibits the phosphorylation of Akt, the phosphorylation of FOXO3a induced by D-gal injection, and finally promotes the expression of antioxidant enzymes SOD2and CAT. At the same time, the saponin from Aralia taibaiensis regulates the MAPKs/Nrf2pathway. It increases the levels of Nrf2and p-Nrf2in the nucleus, improves its transcriptional activity, and then increases the expressions of antioxidant enzyme HO-1, GCLC and GCLM. By activation of these two pathways, the saponin from Aralia taibaiensis improves the antioxidant ability, reduces the ROS damage, thus achieves its anti-aging biological function.