Salidroside inhibits insulin resistance and hepatic steatosis by downregulating miR-21 and subsequent activation of AMPK and upregulation of PPARα in the liver and muscles of high fat diet-fed rats

Zakiah N Almohawes; Attalla El-Kott; Kareem Morsy; Ali A Shati; Ayman E El-Kenawy; Heba S Khalifa; Fahmy G Elsaid; Abd-El-Karim M Abd-Lateif; Ahmed Abu-Zaiton; Eman R Ebealy; Mohamed M Abdel-Daim; Reham A Ghanem; Eman M Abd-Ella

doi:10.1080/13813455.2021.2024578

Salidroside inhibits insulin resistance and hepatic steatosis by downregulating miR-21 and subsequent activation of AMPK and upregulation of PPARα in the liver and muscles of high fat diet-fed rats

Arch Physiol Biochem. 2022 Jan 21:1-18. doi: 10.1080/13813455.2021.2024578. Online ahead of print.

Authors

Zakiah N Almohawes¹, Attalla El-Kott^{2

3}, Kareem Morsy^{2

4}, Ali A Shati², Ayman E El-Kenawy⁵, Heba S Khalifa³, Fahmy G Elsaid^{2

6}, Abd-El-Karim M Abd-Lateif⁷, Ahmed Abu-Zaiton⁸, Eman R Ebealy², Mohamed M Abdel-Daim^{9

10}, Reham A Ghanem¹¹, Eman M Abd-Ella^{7

12}

Affiliations

¹ Biology Department, College of Science, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia.
² Biology Department, College of Science, King Khalid University, Abha, Saudi Arabia.
³ Zoology Department, College of Science, Damanhour University, Damanhour, Egypt.
⁴ Zoology Department, College of Science, Cairo University, Cairo, Egypt.
⁵ Pathology Department, College of Medicine, Taif University, Taif, Saudi Arabia.
⁶ Zoology Department, Faculty of Science, Mansoura University, Mansoura, Egypt.
⁷ Zoology Department, College of Science, Fayoum University, Fayoum, Egypt.
⁸ Biology Department, Al-al-Bayt University, Almafraq, Jordon.
⁹ Pharmaceutical Sciences Department, Pharmacy Program, Batterjee Medical College, Jeddah, Saudi Arabia.
¹⁰ Pharmacology Department, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, Egypt.
¹¹ Oral Biology Department, Faculty of Oral and Dental Medicine, Delta University for Science and Technology, Gamasa, Egypt.
¹² Biology Department, College of Science and Art, Al-Baha University, Al-Mandaq, Saudi Arabia.

PMID: 35061559
DOI: 10.1080/13813455.2021.2024578

Abstract

This study evaluated if salidroside (SAL) alleviates high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) by downregulating miR-21. Rats (n = 8/group) were treated for 12 weeks as normal diet (control/ND), ND + agmoir negative control (NC) (150 µg/kg), ND + SAL (300 mg/kg), HFD, HFD + SAL, HFD + compound C (an AMPK inhibitor) (200 ng/kg), HFD + SAL + NXT629 (a PPAR-α antagonist) (30 mg/kg), and HFD + SAL + miR-21 agomir (150 µg/kg). SAL improved glucose and insulin tolerance and preserved livers in HFD-fed rats. In ND and HFD-fed rats, SAL reduced levels of serum and hepatic lipids and the hepatic expression of SREBP1, SREBP2, fatty acid (FA) synthase, and HMGCOAR. It also activated hepatic Nrf2 and increased hepatic/muscular activity of AMPK and levels of PPARα. All effects afforded by SAL were prevented by CC, NXT629, and miR-21 agmoir. In conclusion, activation of AMPK and upregulation of PPARα mediate the anti-steatotic effect of SAL.

Keywords: HFD; NAFLD; SREBPs; insulin resistance; miR-21; rats; salidroside; steatosis.