Oral bioavailability and amelioration of high fat diet induced obesity via AMPK/SIRT1 pathway using oleoresin from Nigella sativa L. seeds in C57BL/6 mice

Objective: This study investigated the oral bioavailability and anti-obesity effects of oleoresin extracted from
seeds of Nigella sativa L. (NS), in high-fat-diet-fed C57BL/6 mice. NS is rich in polyphenols, flavonoids, and
unsaturated fatty acids; known for their anti-oxidant and anti-inflammatory activity. However, its role in
modulating lipid and energy metabolism remains unexplored.
Methods: Oleoresin was administered orally as well as intravenously (IV), and whole blood was collected at
predetermined time points. Thymoquinone (TQ) concentration in plasma was quantified using HPLC. For anti-
obesity assessment, 36 male C57BL/6 mice were divided into six groups, one normal diet and five HFD
groups. NS oleoresin was administered daily at doses 50, 100, and 200 mg/kg body weight (BW) for 8 weeks.
Results: Treatment groups showed significant reductions in body weight, blood glucose, LDL, triglycerides, total
cholesterol, and liver size, along with an increase in HDL levels. Gene expression analysis revealed that oleoresin
downregulated CCAAT/enhancer-binding protein alpha (C/EBPα) and peroxisome proliferator-activated recep-
tor gamma (PPARγ) expression, while slightly upregulating adenosine monophosphate-activated protein kinase
(AMPKα) gene in the higher dose group. Although the mitochondrial uncoupling protein (UCP1) was not
significantly altered, expression of sirtuin 1 and PGC-1, was enhanced indicating enhanced mitochondrial
biogenesis, insulin sensitivity and weight reduction. Histopathological examination showed reversal of hepatic
steatosis, as well as regular-sized adipocytes in dose-dependent treatment.
Conclusion: NS seed oleoresin supplementation may reduce the BW and lipid profile induced by HFD when given
in higher doses via activation of AMPK/SIRT1 pathway, potentially serving as a functional food therapeutic
against obesity and related complications.