The seed oil of Carapa guianensis Aublet (Andiroba) has been used in
folk medicine for its insect-repelling, anti-inflammatory, and
anti-malarial activities. This study aimed to examine the
triglyceride (TG) reducing effects of C. guianensis-derived
limonoids or other commercially available
limonoids in human
hepatoblastoma HepG2 cells and evaluate the expression of lipid metabolism or
autophagy-related proteins by treatment with 7-deacetoxy-7-oxogedunin (DAOG; 1), a principal
limonoid of C. guianensis. The
gedunin-type
limonoids, such as DAOG (% of control at 20 μM: 70.9 ± 0.9%),
gedunin (2, 74.0 ± 1.1%),
epoxyazadiradione (4, 73.4 ± 2.0%), 17β-hydroxyazadiradione (5, 79.9 ± 0.6%), 7-deacetoxy-7α-hydroxygedunin (6, 61.0 ± 1.2%), andirolide
H (7, 87.4 ± 2.2%), and 6α-hydroxygedunin (8, 84.5 ± 1.1%), were observed to reduce the TG content at lower concentrations than
berberine chloride (BBR, a positive control, 84.1 ± 0.3% at 30 μM) in HepG2 cells pretreated with high
glucose and
oleic acid. Andirobin-, obacunol-,
nimbin-, and
salannin-type
limonoids showed no effect on the intracellular TG content in HepG2 cells. The TG-reducing effect of DAOG was attenuated by the concomitant use of
compound C (dorsomorphin), an AMPK inhibitor. Further investigation on the detailed mechanism of action of DAOG at non-cytotoxic concentrations revealed that the expressions of
autophagy-related proteins, LC3 and p62, were upregulated by treatment with DAOG. These findings suggested that
gedunin-type
limonoids from Andiroba could ameliorate
fatty liver, and that the action of DAOG in particular is mediated by autophagy.