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Food-Derived beta-Carboline Alkaloids Ameliorate Lipid Droplet Accumulation in Human Hepatocytes

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Title: Food-Derived beta-Carboline Alkaloids Ameliorate Lipid Droplet Accumulation in Human Hepatocytes
Authors: Dibwe, Dya Fita Browse this author
Oba, Saki Browse this author
Takeishi, Nire Browse this author
Sakurai, Toshihiro Browse this author
Tsukui, Takayuki Browse this author →KAKEN DB
Chiba, Hitoshi Browse this author →KAKEN DB
Hui, Shu-Ping Browse this author →KAKEN DB
Keywords: functional foods
Crassostrea gigas
beta-carboline alkaloids
bioactive compounds
lipid droplet accumulation inhibition
neutral lipids
Issue Date: 5-May-2022
Publisher: MDPI
Journal Title: Pharmaceuticals
Volume: 15
Issue: 5
Start Page: 578
Publisher DOI: 10.3390/ph15050578
PMID: 35631404
Abstract: Lipid droplet accumulation (LDA) in hepatocytes is the initial stage of nonalcoholic fatty liver disease (NAFLD). In the search for natural compounds for the prevention of NAFLD, a series of beta-carboline alkaloid derivatives, inspired by flazin and its derivative, newly identified in Crassostrea gigas Thunberg. extracts, were examined for LDA inhibition (LDAI) activity in oleic acid-loaded hepatocytes (HepG2). Eight compounds with a piperidine or pyridine C-ring were chemically synthesized (1-8). Among them, compounds 2 and 4 (flazin) with a carboxy group at C-3 and furfuryl alcohol moiety at C-1 showed low cytotoxicity and they exhibited significant LDAI activity. Compound 2 with piperidine C-ring was identified for the first time in C. gigas extract, and ameliorated the lipid accumulation with the LDAI value of 25.4%. Active compounds 2 and 4 significantly inhibited triacylglycerol species accumulation in cells. These compounds upregulated ATGL and downregulated SREBP1, FASN, and SCD1 genes, suggesting that they activated lipolysis and suppressed lipogenesis, respectively. These results suggest that beta-carboline alkaloids, especially compounds 2 and 4, might be potentially useful for preventing NAFLD.
Type: article
Appears in Collections:保健科学院・保健科学研究院 (Graduate School of Health Sciences / Faculty of Health Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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