An in vitro investigation of the effects of urolithins A and B on low-density lipoprotein uptake and its regulatory genes

Shiva Ganjali; Maryam Matbou Riahi; Khadijeh Mahboobnia; Milad Iranshahy; Maciej Banach; Ali Jangjoo; Sorour Ashari; Zahra Tayarani-Najaran; Amirhossein Sahebkar

doi:10.5114/aoms/168120

An in vitro investigation of the effects of urolithins A and B on low-density lipoprotein uptake and its regulatory genes

Arch Med Sci. 2023 Jun 13;19(6):1832-1841. doi: 10.5114/aoms/168120. eCollection 2023.

Authors

Shiva Ganjali¹, Maryam Matbou Riahi², Khadijeh Mahboobnia³, Milad Iranshahy⁴, Maciej Banach^{5

6}, Ali Jangjoo⁷, Sorour Ashari², Zahra Tayarani-Najaran^{8

9}, Amirhossein Sahebkar^{2

10

11}

Affiliations

¹ IMPACT - the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Faculty of Health, Deakin University, Geelong, Vic, Australia.
² Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
³ Department of Biochemistry, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
⁴ Department of Pharmacognosy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
⁵ Department of Preventive Cardiology and Lipidology, Chair of Nephrology and Hypertension, Medical University of Lodz, Lodz, Poland.
⁶ Cardiovascular Research Centre, University of Zielona Gora, Zielona Gora, Poland.
⁷ Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
⁸ Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
⁹ Surgical Oncology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
¹⁰ Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
¹¹ Department of Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.

Abstract

Introduction: This study aimed to evaluate the possible role of urolithin A (UA) and urolithin B (UB) on the mRNA expression levels of LDL receptor (LDLR) and PSCK9 genes, and also of the uptake of LDL particles in HepG2 cells.

Material and methods: The potential role of UA and UB on the induction of LDL uptake and the expression of its regulatory genes was explored using HepG2 cells and curcumin (20 μM), berberine (50 μM), UA (80 μM), and UB (80 μM) as the treatments in the experimental tests.

Results: The LDL uptake and cell-surface LDLR were higher in cells treated with UA in comparison with cells treated with UB, and even in relation to the cells treated with curcumin and berberine as positive controls. In addition, cells treated with UB showed approximately 2 times greater LDLR expression levels compared with curcumin (FC = 2.144, p = 0.013) and berberine (FC = 2.761, p = 0.006). However, UA treatment resulted in significantly lower expression levels of LDLR compared with curcumin (FC = 0.274, p < 0.001) and berberine (FC = 0.352, p = 0.009). UB demonstrated approximately 8 times higher LDLR expression levels when compared with UA (FC = 7.835, p = 0.001). Compared with UB, as well as curcumin and berberine as positive controls, UA was more efficient in reducing PCSK9 expression levels. Although UB did not show any significant differences compared with curcumin and berberine, it showed higher levels of PCSK9 expression when compared with the UA group (FC = 3.694, p < 0.001).

Conclusions: The present results suggest that UA was more effective than UB in promoting LDL uptake as well as cell surface LDLR in HepG2 cells. This effect seems to be mostly mediated through the suppression of PCSK9 expression but not the induction of LDLR expression.

Keywords: HepG2; LDL receptor; LDL uptake; PCSK9; urolithin A; urolithin B.