Ursolic acid attenuates beta-amyloid-induced memory impairment in mice

Abstract

Objective Increasing evidence demonstrates that oxidative stress and inflammatory are involved in amyloid β (Aβ)-induced memory impairments. Ursolic acid (UA), a triterpenoid compound, has potent anti-inflammatory and antioxidant activities. However, it remains unclear whether UA attenuates Aβ-induced neurotoxicity. Method The aggregated Aβ25-35 was intracerebroventricularly administered to mice. Results We found that UA significantly reversed the Aβ25-35-induced learning and memory deficits. Our results indicated that one of the potential mechanisms of the neuroprotective effect was attenuating the Aβ25-35-induced accumulation of malondialdehyde (MDA) and depletion of glutathione (GSH) in the hippocampus. Furthermore, UA significantly suppressed the upregulation of IL-1β, IL-6, and tumor necrosis-α factor levels in the hippocampus of Aβ25-35-treated mice. Conclusion These findings suggest that UA prevents memory impairment through amelioration of oxidative stress, inflammatory response and may offer a novel therapeutic strategy for the treatment of Alzheimer’s disease.

Neuroprotective Effect of ent-Kaur-15-en-17-al-18-oic Acid on Amyloid Beta Peptide-Induced Oxidative Apoptosis in Alzheimer’s Disease

“…It is widely accepted that soluble oligomers Aβ triggers the onset of AD mainly through its interaction with brain parenchyma [29][30][31][32]. Aβ [25][26][27][28][29][30][31][32][33][34][35] , short toxic segment corresponding to amino acids 25-35, has full protein encompassing β-sheet [33]. Therefore Aβ [25][26][27][28][29][30][31][32][33][34][35] has been regarded as vitro model of AD.…”

“…3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay was used to detect LL-3 (chemical structure as shown in Figure 1) [26] cytotoxicity in SH-SY5Y cells. According to Figure 2B, dosage 2.5-20 µM that showed no significant alternation compared to control cells were adopted to detect the LL-3 neuroprotective role in amyloid beta peptide [25][26][27][28][29][30][31][32][33][34][35] )-induced cytotoxicity in SH-SY5Y cells. As Figure 2C shows, LL-3 reversed the cytotoxic activity caused by Aβ [25][26][27][28][29][30][31][32][33][34][35] .…”

“…The assay showed that SH-SY5Y cells treated with Aβ 25-35 alone caused great elevation of ROS production compared to the control group. LL-3 significantly reduced the ROS level with G-mean at 2.5 µM (0.49), 5 µM (0.44), 10 µM, (0.39), 20 µM (0.31) ( Figure 3A), implying that LL-3 may relieve oxidative stress induced by Aβ [25][26][27][28][29][30][31][32][33][34][35] .…”

“…GSH and SOD react with oxyradicals and MDA causes oxidative stress. The results found that the levels of GSH and SOD significantly increased and level of MDA decreased in a dose-independent way through LL-3 co-treatment compared to Aβ [25][26][27][28][29][30][31][32][33][34][35] alone ( Figure 3B-D), suggesting that LL-3 may improve the anti-oxidant system to relive oxidative stress caused by Aβ 25-35 .…”

“…When cells are in mitochondrial apoptotic status, they can form apoptotic bodies including nuclear fragments and organelle which can be stained by diamidino-2-phenylindole (DAPI). In the Aβ [25][26][27][28][29][30][31][32][33][34][35] treated alone group, massive cells with apoptotic bodies were detected under fluorescent microscope. While exposed to LL-3 (5, 10, 20 µM) this phenomenon can be significantly reversed ( Figure 5A).…”