Garcinoic acid (GA or δ-T3-13'COOH), is a natural vitamin E metabolite that has preliminarily been identified as a modulator of nuclear receptors involved in β-amyloid (Aβ) metabolism and progression of Alzheimer's disease (AD). In this study, we investigated GA's effects on Aβ oligomer formation and deposition. Specifically, we compared them with those of other vitamin E analogs and the soy isoflavone genistein, a natural agonist of peroxisome proliferator–activated receptor γ (PPARγ) that has therapeutic potential for managing AD. GA significantly reduced Aβ aggregation and accumulation in mouse cortical astrocytes. Similarly to genistein, GA up-regulated PPARγ expression and apolipoprotein E (ApoE) efflux in these cells with an efficacy that was comparable with that of its metabolic precursor δ-tocotrienol and higher than those of α-tocopherol metabolites. Unlike for genistein and the other vitamin E compounds, the GA-induced restoration of ApoE efflux was not affected by pharmacological inhibition of PPARγ activity, and specific activation of pregnane X receptor (PXR) was observed together with ApoE and multidrug resistance protein 1 (MDR1) membrane transporter up-regulation in both the mouse astrocytes and brain tissue. These effects of GA were associated with reduced Aβ deposition in the brain of TgCRND8 mice, a transgenic AD model. In conclusion, GA holds potential for preventing Aβ oligomerization and deposition in the brain. The mechanistic aspects of GA's properties appear to be distinct from those of other vitamin E metabolites and of genistein.

中文翻译：

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石榴皮酸可防止β-淀粉样蛋白（Aβ）在小鼠大脑中沉积。

石榴皮酸（GA或δ-T3-13'COOH）是一种天然的维生素E代谢物，已被初步鉴定为参与β淀粉样蛋白（Aβ）代谢和阿尔茨海默氏病（AD）进展的核受体的调节剂。在这项研究中，我们研究了GA对Aβ低聚物形成和沉积的影响。具体来说，我们将它们与其他维生素E类似物和大豆异黄酮染料木黄酮（一种过氧化物酶体增殖物激活受体γ（PPARγ）的天然激动剂）进行了比较，该物质具有治疗AD的治疗潜力。GA显着降低了小鼠皮质星形胶质细胞中Aβ的聚集和积累。与金雀异黄素类似，GA上调了这些细胞中的PPARγ表达和载脂蛋白E（ApoE）外排，其功效与其代谢前体δ-生育三烯酚相当，但高于α-生育酚代谢物。与染料木黄酮和其他维生素E化合物不同，GA诱导的ApoE外流恢复不受PPARγ活性的药理抑制作用，并且观察到孕烷X受体（PXR）与ApoE和多药耐药蛋白1（MDR1）的特异性激活）小鼠星形胶质细胞和脑组织中的膜转运蛋白上调。GA的这些作用与转基因AD模型TgCRND8小鼠的大脑中Aβ沉积减少有关。总之，GA具有防止Aβ寡聚和沉积在脑中的潜力。GA'的机械方面