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ETHNOPHARMACOLOGICAL RELEVANCE Cistanche tubulosa is a precious traditional Chinese medicine that has been widely used in the treatment of osteoporosis and Alzheimer's disease. Echinacoside and acteoside are the main active constituents in Cistanche tubulosa that have the pharmacological activities with research value. It has been reported that echinacoside and acteoside could improve the learning and memory ability, promote the proliferation and differentiation of osteoblast. AIM OF STUDY Echinacoside and acteoside from Cistanche tubulosa have shown significant activities of anti-osteoporosis and anti-Alzheimer's disease, while these effects have not been studied concurrently in a rat model. The aim of this study was to establish and verify the model of osteoporosis combined with Alzheimer's disease in rat, and to investigate the double effects of echinacoside and acteoside on this concurrent model. MATERIALS AND METHODS Three model groups of ovariectomy (OVX), sham surgery with D-galactose and AlCl3 (D), ovariectomy with D-galactose and AlCl3 (OVX + D) were set at the same time. The rats in drug treatment groups were ovariectomized. While conducting the intraperitoneal injection of D-galactose and intragastric administration of AlCl3 in the rats of drug treatment groups, the rats were orally administered echinacoside (90 mg/kg/d), acteoside (90 mg/kg/d) and the positive control drugs of estradiol valerate (0.6 mg/kg/d), donepezil HCl (0.8 mg/kg/d), respectively. After the drug treatment of 8 weeks, Morris Water Maze (MWM) test for 6 days was firstly performed. The rats were then sacrificed to harvest the blood, uteri, femora, tibiae and brain tissues. The serum was used for biochemical tests. The uteri were used for histomorphometry. The right femora were used for Micro-CT and histomorphometry, respectively. The right tibiae were used for biomechanical test. The hippocampus collected on ice box was used for biochemical tests. The brain collected by perfusion was used for histomorphometry. RESULTS Compared with Sham group, OVX + D group could significantly reduce the learning and memory ability by causing oxidative damage, impairing neurons in hippocampus and affecting the hydrolysis and synthesis of acetylcholine. Meanwhile, the activities of BALP and TRAP in OVX + D group increased significantly (P < 0.001) as compared to Sham group. In addition, compared with Sham group, the mean bone mineral density obviously decreased (P < 0.05), the trabecular bone mass and microarchitecture were also destroyed significantly in OVX + D group. Furthermore, the maximum load and maximum stress significantly reduced (P < 0.01) and the energy absorption also decreased greatly as compared to Sham group. After administrated with echinacoside and acteoside, the typical pathological features of osteoporosis and Alzheimer's disease were ameliorated. CONCLUSIONS The model of osteoporosis combined with Alzheimer's disease in rat was feasible and successfully established. Echinacoside and acteoside also showed some significant effects on this concurrent model, and they could be potential candidates from Cistanche tubulosa with double effects for further study.