Thymoquinone and quercetin protect against hepatic steatosis in association with SIRT1/AMPK stimulation and regulation of autophagy, perilipin-2, and cytosolic lipases

Abstract

Background

We sought to investigate thymoquinone (TQ)/quercetin combination in preventing hepatic steatosis (HS).

Materials and methods

The included rat groups; (1) Control, (2) HS model, (3) HS treated with TQ 10 mg.kg⁻¹.d⁻¹, (4) HS treated with quercetin 50 mg.kg⁻¹.d⁻¹, and (5) HS treated with both compounds for 4 weeks.

Results

TQ/quercetin co-treatment augmented the anti-steatosis potential of each ingredient. The results revealed more (p < 0.001) sirtuin (SIRT1)/AMP-activated protein kinase (p-AMPK) upregulation compared to each treatment in line with autophagy protein Atg7 enhancement, and suppressed pro-inflammatory and oxidation markers. They diminished the hepatic lipogenic enzymes and perilipin-2 and activated the cytosolic lipases adipose triglyceride lipase (ATGL). Histological and Biochemical analysis revealed diminished lipid deposition and improved liver enzymes (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) compared to the data of separate treatments.

Conclusion

TQ and quercitin effectively upregulated SIRT1/p-AMPK and regulated hepatic perilipin-2/ATGL, inflammation and oxidative stress, preserved liver structure and function. TQ/quercetin combination additively prevents HS.

Keywords:

• Hepatic steatosis
• thymoquinone
• quercetin
• SIRT1/AMPK
• autophagy/perilipin/ATGL

Acknowledgements

The authors extend their appreciation to the Deanship of Scientific Research at King Khalid University for funding this work through the small research group under grant number [RGP.1/163/43]. The authors are grateful to Dr Mariam Al-Ani from Face Studio Clinic, 273 Hagley Road, Birmingham, B16 9NB, UK for proofreading the manuscript.

Author contributions

The idea was initiated by Hend Ashour. The experiments were conducted by Omaima M. Abdelwahed with reference to Hend Ashour. Laila A. Rashed and Radwa T. M. Hassanein was responsible for the biochemical assessment. Basma E. Aboulhoda and Miran A. Elkordy performed the histological examination and writing the corresponding section. Data collection, statistical analysis, expression of the figures and writing the first draft were performed by Hend Ashour, Mohamed H. Elsayed, and Hasnaa A. Ebrahim. The final manuscript was revised and approved by all the contributing authors.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The authors extend their appreciation to the Deanship of Scientific Research at King Khalid University for funding this work through the small research group under grant number [RGP.1/163/43]. The work was also supported by Princess Nourah bint Abdulrahman University Researchers Supporting Project number [PNURSP2022R171], Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.