Bioactive Alkaloids from Nepalese Corydalis chaerophylla D.C. Acting on the Regulation of PCSK9 and LDL-R In Vitro.

Autor: Maharjan B; Department of Chemistry, Amrit Campus, Tribhuvan University, Kathmandu, 44600, Nepal., Rossi I; Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy., Sut S; Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy., Shrestha T; Department of Chemistry, Amrit Campus, Tribhuvan University, Kathmandu, 44600, Nepal., Shrestha LK; Research Center for Materials Nano Architectonics (MANA), National Institute for Materials Science (NIMS), 1-1 Namiki, Tsukuba, Ibaraki, 305-0044, Japan.; Department of Materials Science, Faculty of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8573, Japan., Hill JP; Research Center for Materials Nano Architectonics (MANA), National Institute for Materials Science (NIMS), 1-1 Namiki, Tsukuba, Ibaraki, 305-0044, Japan., Ariga K; Research Center for Materials Nano Architectonics (MANA), National Institute for Materials Science (NIMS), 1-1 Namiki, Tsukuba, Ibaraki, 305-0044, Japan.; Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba, 277-8561, Japan., Benetazzo V; Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy., Adorni MP; Department of Medicine and Surgery, University of Parma, Parma, Italy., Papotti B; Department of Food and Drug, University of Parma, Parma, Italy., Shrestha SS; Himalayan Research and Development Center Nepal, Kathmandu, Nepal., Shrestha RLS; Department of Chemistry, Amrit Campus, Tribhuvan University, Kathmandu, 44600, Nepal., Ferri N; Department of Medicine, University of Padova, Padova, Italy.; Veneto Institute of Molecular Medicine (VIMM), Padova, Italy., Dall'Acqua S; Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy.
Jazyk: angličtina
Zdroj: Chemistry & biodiversity [Chem Biodivers] 2024 Dec; Vol. 21 (12), pp. e202401388. Date of Electronic Publication: 2024 Oct 28.
DOI: 10.1002/cbdv.202401388
Abstrakt: Four new alkaloids Chaeronepaline-A (1), Chaeronepaline-B (2), Chaeronepaline-C (3), and Chaeronepaline-D (4) were isolated from Corydalis chaerophylla D.C. collected from Nepal and their structures were elucidated by spectroscopic data, 1D, 2D NMR and mass spectrometry. The structures were established as 3,12- Dimethoxy-5,6-dihydroisoquinolino [2,1-b] isoquinolin- 7- ium- 2, 9- diol (1), 7-Methyl-2,3 : 11,12-bis(methylenedioxy)-7,13a-secoberbin-13-14-epoxide (2), 7- methyl-5, 6, 7, 8- tetrahydro- 8H-spiro-9,14-dihydroxy-11,12-methylenedioxy-indane-isoquinoline (3) and 7- methyl-5, 6, 7, 8- tetrahydro- 8H-spiro-9,14-dihydroxy-11,12-methylenedioxy-indane-isoquinoline-N-oxide (4). The new alkaloids were tested in human hepatoma cell line to assess their ability to modulate the expression of low-density lipoprotein receptor (LDL-R), of proprotein convertase subtilisin/kexin 9 (PCSK9) and to affect cellular cholesterol biosynthesis with the aim to evaluate their potential hypocholesterolemic effect. Results indicated that compounds 2 and 3 upregulate the LDLR, and inhibited the cholesterol biosynthesis with compound 2, which also reduced the secretion of PCSK9 by Huh7 cells. These in vitro data indicated a potential hypocholesterolemic effect of compound 2 that requires further in vivo validation.
(© 2024 The Author(s). Chemistry & Biodiversity published by Wiley-VHCA AG.)
Databáze: MEDLINE
Externí odkaz: