Thymoquinone ameliorates obesity-induced metabolic dysfunction, improves reproductive efficiency exhibiting a dose-organ relationship

ABSTRACT

Women with obesity are more likely to have a complicated reproductive life. Insulin resistance and metabolic dysfunction are associated with obesity. Thymoquinone (TQ) is a well-known antioxidant, considered to be an AMPK-activator. The goal of this work was to investigate the ability of TQ to improve fertility and lactation and clarify the possible mechanism. Female C57BL/6 mice were subjected to High Fat Diet (HFD) supplemented with TQ (10% pmm) and TQ (20% pmm). Histopathological examination was conducted on mammary and ovarian samples. Metabolic and oxidant status was evaluated, and qRT-PCR analysis was performed to verify AMPK/PGC1α/SIRT1 metabolic pathway activity. The present study reports positive effects of TQ on ovarian metabolic function in a dose-dependent manner. TQ showed its positive effects on mammary gland metabolic function at lower dose. This is the first study that indicates these dose related impacts of TQ.

Abbreviations: AKT1: serine-threonine protein kinase 1; AMPK: 5′ AMP-activated protein kinase; CAT: catalase; CON: control; FBS: fasting blood sugar; GLUT1: glucose transporter 1; GSH: reduced glutathione; GSSG: Glutathione disulfide; HE: hematoxylin and eosin stains; HDL: high-density lipoprotein; HFD: high fat diet; IL-6: interleukin-6; K18: keratin 18; LD: lactation day; LDL: low-density lipoprotein; LKB1: serine-threonine liver kinase B1; MDA: malondialdehyde; mTOR: the mammalian target of rapamycin; NAD: nicotinamide adenine dinucleotide; NADH: nicotinamide adenine dinucleotide phosphate; NS: nigella sativa; PBS: phosphate-buffered saline; PGC1α: peroxisome proliferator-activated receptor gamma coactivator 1-alpha; SIRT1: sirtuin 1; SOD: superoxide dismutase; T-AOC: total antioxidants; TFAM: transcription factor A mitochondrial; TG: triglycerides; TNF-α: tumor necrosis factor-α; TQ: thymoquinone; TQ10: high fat diet + thymoquinone 10% ppm; TQ20: high fat diet + thymoquinone 20% ppm; UCP2: uncoupling Protein 2.

KEYWORDS:

• Thymoquinone
• lactation
• fertility
• metabolic dysfunction
• obesity

Acknowledgments

The authors are very thankful to Prof. Guowei Le for his support and guides during the research work. We are also very thankful to the State Key Laboratory of Food Science and Technology of Jiangnan University for providing facilities and all necessary equipment.

Disclosure statement

No potential conflict of interest was reported by the authors.

Authors’ contributions

Responsible for the concept and design of the studies: GWL, YHS; Carried out the whole mount, H&E, the histopathological evaluation, RT-PCR procedure, and wrote the manuscript: SH; Carried out the assay of oxidative stress, plasma parameters, and analyzed the data: GQW; Assisted with the animal experiments: MG, GQ; Edited the manuscript: MZ.

Additional information

Funding

This work was supported by the 1State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi [214122];the National Natural Science Foundation of China [31571841].