Identification of Picrasidine C as a Subtype-Selective PPARα Agonist

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• 作者：Shuai Zhao ; Yuichiro Kanno ; Wei LiTatsunori Sasaki ; Xiangyu Zhang ; Jian Wang ; Maosheng Cheng ; Kazuo Koike ; Kiyomitsu Nemoto ; Huicheng Li
• 刊名：Journal of Natural Products
• 出版年：2016
• 出版时间：December 23, 2016
• 年：2016
• 卷：79
• 期：12
• 页码：3127-3133
• 全文大小：510K
• ISSN：1520-6025

文摘

Picrasidine C (1), a dimeric β-carboline-type alkaloid isolated from the root of Picrasma quassioides, was identified to have PPARα agonistic activity by a mammalian one-hybrid assay from a compound library. Among the PPAR subtypes, 1 selectively activated PPARα in a concentration-dependent manner. Remarkably, 1 also promoted PPARα transcriptional activity by a peroxisome proliferator response element-driven luciferase reporter assay. Furthermore, 1 induced the expression of PPARα-regulated genes involved in lipid, glucose, and cholesterol metabolism, such as CPT-1, PPARα, PDK4, and ABCA1, which was abrogated by the PPARα antagonist MK-886, indicating that the effect of 1 was dependent on PPARα activation. This is the first report to demonstrate 1 to be a subtype-selective PPARα agonist with potential application in treating metabolic diseases, such as hyperlipidemia, atherosclerosis, and hypercholesterolemia.