The effect of black seed (Nigella sativa) extract on lipid metabolism in HepG2 cells

Black seed extract stimulates apolipoprotein A-I (apo A-I) gene expression in hepatocytes and intestinal cells in part by elevating peroxisome proliferator-activated receptor alpha (PPAR alpha) and retinoid X receptor alpha (RXR alpha) levels. To explore potential ramifications of these observations, we examined the effects of black seed extract on hepatocyte lipid content and expression of key transcriptional regulators of fatty acid beta-oxidation and lipogenesis in HepG2 cells. PPAR alpha, peroxisome proliferator-activated receptor gamma (PPAR gamma), RXR alpha, thyroid hormone receptor beta (TR beta), sterol-responsive element binding protein 1 (SREBP1), and sterol-responsive element binding protein 2 (SREBP2) levels were measured in black seed extract treated liver-derived HepG2 cells. Black seed extract treatment increased PPAR alpha and RXR alpha expression and decreased intracellular neutral lipid content. Black seed extract treatment increased TR beta expression and activity, and PPAR alpha activity. In contrast, PPAR gamma, SREBP1 and SREBP2 levels were decreased in black seed extract treated cells. Black seed extract treatment also increased acyl-CoA synthetase long chain family member 5 (ACSL5), peroxisomal acyl-CoA oxidase 1 (ACOX1), and carnitine palmitoyl transferase 1A (CPT-1A) expression, three PPAR alpha-dependent rate-limiting genes that facilitate fatty acid oxidation, similar to fenofibrate. PPAR alpha knockdown reversed the effects of fenofibrate and blackseed on ACSL5, ACOX1, and CPT-1A expression. In conclusion, black seed extract-mediated lipid lowering in HepG2 cells is associated with increased expression of fatty acid oxidation enzymes and PPAR alpha and reduced lipogenic signaling. Thus black seed extract may be potentially beneficial in metabolic diseases such as diabetes, cardiovascular disease, and metabolic syndrome.

Automated summary

Black seed extract stimulates the expression of apo A-I gene and elevates the levels of PPAR alpha and RXR alpha. In HepG2 cells, it reduces lipid content and affects the expression of key regulators of fatty acid metabolism. It also increases the expression of fatty acid oxidation enzymes and reduces lipogenic signaling. Therefore, black seed extract may have potential benefits in metabolic diseases.