Molecular mechanism of DLBS3733, a bioactive fraction of Lagerstroemia speciosa (L.) Pers., on ameliorating hepatic lipid accumulation in HepG2 cells

Abstract

Ethnopharmacological relevanceLagerstroemia speciosa (L.) Pers., commonly known as banaba and locally known as bungur, is widely used in Indonesia and other countries as a folk remedy for various chronic diseases such as diabetes mellitus and hypertension. L. speciosa (L.) Pers. has been used and evaluated on conditions associated to liver diseases by altering cholesterol absorption, lipid metabolism, as well as the related gene expressions. Aim of the studyThe aim of this study is to evaluate the effect of DLBS3733, a standardized bioactive fraction of Lagerstroemia speciosa (L.) Pers. leaves, on ameliorating hepatic steatosis induced by oleic acid, and elucidate its mechanism of action to ameliorate lipid accumulation in HepG2 cells. Materials and methodsEffects of DLBS3733 on expression of genes and proteins associated with lipid metabolism were evaluated in HepG2 cells in this study. Genes associated with lipid metabolism were evaluated using PCR, while the protein levels were revealed using western blot and ELISA. Cellular lipid accumulations and triglyceride (TG) synthesis were measured using ELISA, and antioxidant assay was conducted using DPPH assay. ResultsDLBS3733 significantly reduced lipid accumulation and TG synthesis by 51% and 32% (p < 0.01), respectively, through the significant increment of adiponectin expression by 58% (p < 0.01). Subsequently, adiponectin enhanced PPARα expression and AMPK phosphorylation which further regulate the downstream signaling pathway of lipogenesis and lipolysis. Moreover, 2.5 µg/mL DLBS3733 was found to significantly downregulate the expression of HMGCR, ACC and SREBP by 66%, 61% and 36%, respectively (p < 0.01), as well as significantly upregulate CPT-1 by 300% at the protein level (P < 0.05). DLBS3733 was also found to possess high antioxidant activity, where the highest concentration exhibited DPPH inhibition activity by up to 93% (P < 0.01). ConclusionsWe propose that DLBS3733 may provide a prevention on hepatic steatosis through its activity as anti-lipogenesis, anti-cholesterologenesis and pro-lipolysis in HepG2 cells. This is the first report that revealed the molecular mechanism of L. speciosa (L.) Pers. as a potential treatment of hepatic steatosis-related diseases.