从具有过氧化物酶体增殖物激活受体-α（PPAR-α）活性研究中鉴定新的聚乙炔类化合物。

Identification of New Polyacetylenes from with PPAR-α Activity Study.

作者信息

Piao Donglan, Youn Isoo, Huynh Thanh-Hau, Kim Hyun Woo, Noh Sang Gyun, Chung Hae Young, Oh Dong-Chan, Seo Eun Kyoung

机构信息

Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul 03760, Republic of Korea.

Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.

出版信息

Molecules. 2024 Dec 16;29(24):5942. doi: 10.3390/molecules29245942.

DOI:10.3390/molecules29245942

PMID:39770031

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11677830/

Abstract

Leveille is a traditional medicine used to treat migraine headache and dysmenorrhea. In this study, three polyacetylenes, methyl (10,9,16)-16-acetoxy-9-hydroxyoctadeca-10,17-dien-12,14-diynoate (), methyl (10,9,16)-9,16-dihydroxyoctadeca-10-en-12,14-diynoate (), and methyl (10,9,16)-9,16-dihydroxyoctadeca-10,17-dien-12,14-diynoate (), were isolated from the aerial parts of . , together with seven known compounds (-). Importantly, the isolates ( and ) were found in the family Araliaceae for the first time in this study. Compounds - were evaluated for their binding affinity to AMPK and CTSS receptors using in silico docking simulations. Only compound increased the protein expression levels of PPAR-α, Sirt1, and AMPK when administered to HepG2 cells as a PPAR-α agonist. On the other hand, did not produce any significant reduction in CTSS activity. This study could pave the way for the discovery of novel treatments from targeting PPAR-α and AMPK.

摘要

勒韦尔是一种用于治疗偏头痛和痛经的传统药物。在本研究中，从[植物名称]的地上部分分离出三种聚乙炔类化合物，即(10,9,16)-16-乙酰氧基-9-羟基十八碳-10,17-二烯-12,14-二炔酸甲酯（）、(10,9,16)-9,16-二羟基十八碳-10-烯-12,14-二炔酸甲酯（）和(10,9,16)-9,16-二羟基十八碳-10,17-二烯-12,14-二炔酸甲酯（），还分离出七种已知化合物（-）。重要的是，在本研究中首次在五加科植物中发现了分离物（和）。使用计算机对接模拟评估了化合物-对AMPK和CTSS受体的结合亲和力。当作为PPAR-α激动剂施用于HepG2细胞时，只有化合物增加了PPAR-α、Sirt1和AMPK的蛋白表达水平。另一方面，没有使CTSS活性产生任何显著降低。这项研究可能为从[植物名称]中发现靶向PPAR-α和AMPK的新疗法铺平道路。