Food-Derived β-Carboline Alkaloids Ameliorate Lipid Droplet Accumulation in Human Hepatocytes
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 β-carboline alkaloid derivatives, inspired by flazin and its derivative, newly identified in <i>Crassos...
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| Main Authors: | , , , , , , |
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| Format: | Book |
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MDPI AG,
2022-05-01T00:00:00Z.
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| Summary: | 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 β-carboline alkaloid derivatives, inspired by flazin and its derivative, newly identified in <i>Crassostrea gigas</i> 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 (<b>1</b>-<b>8</b>). Among them, compounds <b>2</b> and <b>4</b> (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 <b>2</b> with piperidine C-ring was identified for the first time in <i>C. gigas</i> extract, and ameliorated the lipid accumulation with the LDAI value of 25.4%. Active compounds <b>2</b> and <b>4</b> significantly inhibited triacylglycerol species accumulation in cells. These compounds upregulated <i>ATGL</i> and downregulated <i>SREBP1</i>, <i>FASN</i>, and <i>SCD1</i> genes, suggesting that they activated lipolysis and suppressed lipogenesis, respectively. These results suggest that β-carboline alkaloids, especially compounds <b>2</b> and <b>4</b>, might be potentially useful for preventing NAFLD. |
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| Item Description: | 10.3390/ph15050578 1424-8247 |