2. Academic Validation
  3. Isocoumarins and Benzoquinones with Their Proprotein Convertase Subtilisin/Kexin Type 9 Expression Inhibitory Activities from Dried Roots of Lysimachia vulgaris

Isocoumarins and Benzoquinones with Their Proprotein Convertase Subtilisin/Kexin Type 9 Expression Inhibitory Activities from Dried Roots of Lysimachia vulgaris

  • ACS Omega. 2022 Dec 8;7(50):47296-47305. doi: 10.1021/acsomega.2c06660.
Pisey Pel 1,  Young-Mi Kim 1,  Hyun Ji Kim 2,  Piseth Nhoek 1,  Chae-Yeong An 1,  Min-Gyung Son 1,  Hongic Won 1,  Seung Eun Lee 3,  Jeonghoon Lee 3,  Hyun Woo Kim 2,  Young Hee Choi 2,  Chang Hoon Lee 2,  Young-Won Chin 1
Affiliations

Affiliations

  • 1 College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, 1, Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea.
  • 2 College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University-Seoul, 32 Dongguk-lo, Ilsandong-gu, Goyang-si, Gyeonggi-do 10326, Republic of Korea.
  • 3 Department of Herbal Crop Research, National Institute of Horticultural and Herbal Science (NIHHS) of Rural Development Administration, Eumseong 27709, Republic of Korea.
PMID: 36570277 DOI: 10.1021/acsomega.2c06660
Abstract

A phytochemical investigation of the n-hexane-soluble chemical constituents of Lysimachia vulgaris roots allowed for selection using a proprotein convertase subtilisin-kexin type 9 (PCSK9) mRNA expression monitoring assay in HepG2 cells. This led to the isolation of two previously undescribed isocoumarins of natural origin, 8'Z,11'Z-octadecadienyl-6,8-dihydroxyisocoumarin (1) and 3-pentadecyl-6,8-dihydroxyisocoumarin (2), along with 20 previously reported compounds (3-22). All of the structures were established using NMR spectroscopic data and MS analysis. Of the isolates, 1 and 3 were found to inhibit PCSK9, inducible degrader of the low-density lipoprotein receptor (IDOL), and SREBP2 mRNA expression. Further computational dockings of both 1 and 3 to C-ring of IDOL E3 ubiquitin Ligase predicted the mechanism behind the inhibitory effect of these compounds on the Enzyme.

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