Pharmacodynamical Research Of Icariin Combined With Panax Notoginseng Saponins On Alzheimer's Disease Model Rats Induced By β-amyloid Peptide_25-35 Lateral Ventricle Injection

Based on the pathological mechanisms of Alzheimer's disease (AD) in both traditional Chinese medicine and modern medical sciences, as well as the recent studies on the therapeutic effects of Herba Epimedii (HE) and Radix Notoginseng (RN) on either the AD patients or the AD animal models, we adopted the modern isolation methods to study the active components of these two herbs. Icariin (1CA) and Panax notoginseng saponins (PNS) were extracted from HE and RN respectively, and by combined administration of the two extracts, we further observed their therapeutic effects on improving the learning and memory capabilities in a rat AD model, in an attempt to provide some experimental evidence for the preventive and therapeutic effects, as well as the relevant mechanisms of the two herbs in AD treatment.1. Effects of ICA combined with the PNS on spacial learning and memory capabilities induced by β-amyloid peptide 25.3s lateral ventricle injection in rats.After successfully trained by 8-arm radial electric maze and step-down passive avoidance test, the rats were administrated in lateral ventricle with β-AP_25-35 followed by one week of drug treatment. Spacial learning and memory ability were evaluated by 8-arm radial electric maze and Step-down passive avoidance test after a period of drug therapy. The result showed the learning and memory abilities of ratsby lateral ventricle injection with P-AP25-35 significantly decreased compared with that in the saline group, as judged by the 8-arm radial electric maze test (P<0.05) and step-down passive avoidance test (P<0.01). The combination (ICA+PNS 5+40 x 10+80 mg/kg, ig ) significantly protected and improved all the evaluated indexes of the model groups after three weeks(P<0.05).2. Mechanism studies of ICA combined with the PNS on improving special learning and memory capabilities in AD model rats.2.1 Effects of ICA combined with the PNS on Acetylcholinesterase activity in brain of AD model rats.The brain of above rats were sampled after the final behavioral test. The activity of acetylcholinesterase (AchE) in the brain was determined after Homogenate. The results showed the combination (ICA+PNS 5+40 ^ 10+80 mg/kg. ig ) could inhibit the activity of AchE in the brain (P<0.05).2.2 Immunoregulatory studies of icariin combined with the Panax notoginseng saponins in mice by serum pharmacological method.Base on body surface area conversions, the mice were administrated with 8 times of extract combination. The serum was prepared to carry out immunologic study by serum pharmacological methods. Drug-contained serum of ICA + PNS (80+640 mg/kg, 160+1280 mg/kg) group could stimulate the proliferation spleen cell induced by CoA (PO.01, P<0.05). Drug-contained serum of ICA combined with PNS shows cooperation and its dose-effect curve is shapely similar to "PI". None proliferation of spleen cells could be induced by LPS in tested groups (P>0.05). Drug-contained serum of ICA + PNS (80+640 mg/kg, 160+1280 mg/kg) groups could improve IL-2 production (/><0.01). ICA combined with PNS show cooperation and its dose-effect curve is shapely similar to "H" too.Appendix: Other Pharmacodynamical exploration of previous studes.3. The HUO XUE HUA YU effects of HE + RN crude extract combination.The KPTT in rat blood serum was prolonged after the continuous 7-day ig administration of the crude extract of HE plus RN at a dosage of 1.250 and 0.750 g/kg (/J<0.01). It is also observed that HE+RN crude extract combination 1.250+0.750^ 3.750+2.250 g/kg show a strong hemostatic activity on the mice after continuous ig administration for 7 days.4. Effect of HE + RN crude extract combination on amnestic mice model induced by scopolamine hydrobromide injection.Base on primary cognition that the combination have HUO XUE HUA YU effects, we adopt further studies to prove whether the combination could improve intelligence in animals or not. The learning and memory abilities of the mice were significantly decreased after celiac injection with scopolamine hydrobromide injection one time. The behavior of these amnestic mice were significantly improved after continuous ig administration of HE + RN crude extract combination 0.625+0.375 g/kg for 7 days (at a dose of significantly anti-thrombosis effect) before celiac injection with scopolamine hydrobromide injection one time (P>0.05). On the contrary, it took on impaired trend after administration of HE + RN crude extract combination 1.875+1.225 g/kg in same way(at a dose of KPTT in rat blood serum significantly prolonged). We speculate that the extracts are not necessarily the activecomponents in this model. Further studies on the extra active components are needed, as well as other disease models should be included to test the potential effects of these extracts.CONCLUSION1. ICA combined with PNS could significantly protect and improve the spacial learning and memory abilities of AD model rats induced by lateral ventricle injection with P-AP25-35, which suggests that the combination may have preventive and therapeutic effects on AD.2. ICA combined with PNS can inhibit AchE activity of the brain induced by p-amyloid peptide 25.35 lateral ventricle injection in rats, which suggests that improving choline function may is one of the mechanisms by which the combination improve spacial learning and memory abilities.3. Drug-contained rat serum administrated by ICA and PNS could stimulate proliferation of spleen lymphocyte and the secretion of IL-2. The immunoregulatory effects might be one of the mechanisms by which the combination exerts the spacial learning and memory abilities -improving effect.4. HE+RN crude extract combination exhibited marked HUO XUE HUA YU and hemostatic effects, but it can not improve learning and memory abilities of amnestic mice model induced by scopolamine hydrobromide injection.