Amyloid  protein (A) elicits a toxic effect on neurons in vitro and in vivo. In present study we attempt to elucidate the mechanism by which A confers its neurotoxicity. The neuroprotective effects of phytoestrogens on A-mediated toxicity were also investigated. Cortical neurons treated with 5 M A-(25-35) for 40 h decreased the cell viability by 45.5 ؎ 4.6% concomitant with the appearance of apoptotic morphology. 50 M kaempferol and apigenin decreased the A-induced cell death by 81.5 ؎ 9.4% and 49.2 ؎ 9.9%, respectively. A increased the activity of caspase 3 by 10.6-fold and to a lesser extent for caspase 2, 8, and 9. The A-induced activation of caspase 3 and release of cytochrome c showed a biphasic pattern. Apigenin abrogated A-induced cytochrome c release, and the activation of caspase cascade. Kaempferol showed a similar effect but to a less extent. Kaempferol was also capable of eliminating A-induced accumulation of reactive oxygen species. These two events accounted for the remarkable effect of kaempferol on neuroprotection. Quercetin and probucol did not affect the A-mediated neurotoxicity. However, they potentiated the protective effect of apigenin. Therefore, these results demonstrate that A elicited activation of caspase cascades and reactive oxygen species accumulation, thereby causing neuronal death. The blockade of caspase activation conferred the major neuroprotective effect of phytoestrogens. The antioxidative activity of phytoestrogens also modulated their neuroprotective effects on A-mediated toxicity.
The DPPH scavenging effect, the inhibition of human low-density lipoprotein oxidation, and antioxidative contents were employed for the activity-guided purification to identify the antioxidant components of lotus leaves (leaves of Nelumbo nucifera Gaertn.). The methanolic extract of lotus leaves (LLM) was separated into ethyl acetate (LLME), n-butanol (LLMB), and water (LLMW) fractions. LLME and LLMB exhibited greater capacity to scavenge DPPH radical, delayed LDL oxidation, and had higher antioxidative contents than LLMW. Seven flavonoids were isolated from both fractions by column chromatography. On the basis of 1D- and 2D-NMR experiments and MS data analyses, these compounds were identified as catechin (1), quercetin (2), quercetin-3-O-glucopyranoside (3), quercetin-3-O-glucuronide (4), quercetin-3-O-galactopyranoside (5), kaempferol-3-O-glucopyranoside (6), and myricetin-3-O-glucopyranoside (7). Quercetin and its glycosides (compounds 2-5) exerted potent inhibition of LDL oxidation, whereas myricetin-3-O-glucopyranoside (7) showed stronger DPPH scavenging activity. These results indicate that the antioxidant capacity of lotus leaves is partially relevant to its flavonoids.
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