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

Dya Fita Dibwe; Saki Oba; Nire Takeishi; Toshihiro Sakurai; Takayuki Tsukui; Hitoshi Chiba; Shu-Ping Hui

doi:10.3390/ph15050578

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

Pharmaceuticals (Basel). 2022 May 5;15(5):578. doi: 10.3390/ph15050578.

Authors

Dya Fita Dibwe¹, Saki Oba², Nire Takeishi², Toshihiro Sakurai¹, Takayuki Tsukui³, Hitoshi Chiba³, Shu-Ping Hui¹

Affiliations

¹ Faculty of Health Sciences, Hokkaido University, Kita-12, Nishi-5, Kita-Ku, Sapporo 060-0812, Japan.
² Graduate School of Health Sciences, Hokkaido University, Kita-12, Nishi-5, Kita-Ku, Sapporo 060-0812, Japan.
³ Department of Nutrition, Sapporo University of Health Sciences, Nakanuma Nishi-4-3-1-15, Higashi-Ku, Sapporo 007-0894, Japan.

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 β-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 β-carboline alkaloids, especially compounds 2 and 4, might be potentially useful for preventing NAFLD.

Keywords: Crassostrea gigas; bioactive compounds; functional foods; lipid droplet accumulation inhibition; lipidomics; neutral lipids; triacylglycerols; β-carboline alkaloids.

Grants and funding

This research was supported by (1) the Startup Research grant and research grant from the Faculty of Health Science at Hokkaido University (870411H) to D.F.D and (2) the Japan Society for the Promotion of Science (JSPS) KAKENHI (19K07861) grant to S.-P.H.