精神活性化合物白术内酯（BD）在阿尔茨海默病中的神经保护作用。

Neuroprotective Effects of the Psychoactive Compound Biatractylolide (BD) in Alzheimer's Disease.

机构信息

The Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, and Department of Pharmacy, School of Medicine, Hunan Normal University, Changsha 410013, China.

College of Letters & Science, University of California, Berkeley, CA 94720, USA.

出版信息

Molecules. 2022 Nov 28;27(23):8294. doi: 10.3390/molecules27238294.

Mitochondria play a central role in the survival or death of neuronal cells, and they are regulators of energy metabolism and cell death pathways. Many studies support the role of mitochondrial dysfunction and oxidative damage in the pathogenesis of Alzheimer's disease. Biatractylolide (BD) is a kind of internal symmetry double sesquiterpene novel ester compound isolated from the Chinese medicinal plant Baizhu, has neuroprotective effects in Alzheimer's disease. We developed a systematic pharmacological model based on chemical pharmacokinetic and pharmacological data to identify potential compounds and targets of Baizhu. The neuroprotective effects of BD in PC12 (rat adrenal pheochromocytoma cells) and SH-SY5Y (human bone marrow neuroblastoma cells) were evaluated by in vitro experiments. Based on the predicted results, we selected 18 active compounds, which were associated with 20 potential targets and 22 signaling pathways. Compound-target, target-disease and target-pathway networks were constructed using Cytoscape 3.2.1. And verified by in vitro experiments that BD could inhibit Aβ by reducing oxidative stress and decreasing CytC release induced mPTP opening. This study provides a theoretical basis for the development of BD as an anti-Alzheimer's disease drug.

线粒体在神经元细胞的存活或死亡中起着核心作用，它们是能量代谢和细胞死亡途径的调节剂。许多研究支持线粒体功能障碍和氧化损伤在阿尔茨海默病发病机制中的作用。白术内酯（BD）是从中药白术中分离得到的一种内对称双倍半萜新型酯类化合物，具有治疗阿尔茨海默病的神经保护作用。我们基于化学药代动力学和药理学数据开发了一个系统的药理学模型，以鉴定白术的潜在化合物和靶点。通过体外实验评估了 BD 在 PC12（大鼠肾上腺嗜铬细胞瘤细胞）和 SH-SY5Y（人骨髓神经母细胞瘤细胞）中的神经保护作用。基于预测结果，我们选择了 18 种活性化合物，它们与 20 个潜在靶点和 22 个信号通路相关。使用 Cytoscape 3.2.1 构建化合物-靶标、靶标-疾病和靶标-通路网络，并通过体外实验验证 BD 可以通过减少氧化应激和降低 CytC 释放诱导的 mPTP 开放来抑制 Aβ。本研究为将 BD 开发为治疗阿尔茨海默病的药物提供了理论依据。