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Published April 1, 2022 | Version 1
Journal article Open

Anti-adipogenic activity of maackiain and ononin is mediated via inhibition of PPARγ in human adipocytes

  • 1. BB-NCIPD Ltd., BB-National Centre of Infectious and Parasitic Diseases, Ministry of Health, 1000 Sofia, Bulgaria
  • 2. Department of Plant Cell Biotechnology, Center of Plant Systems Biology and Biotechnology, 4000, Plovdiv, Bulgaria; Laboratory of Metabolomics, Department of Biotechnology, The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 4000, Plovdiv, Bulgaria
  • 3. Department of Pharmacy, G. d′Annunzio University, 66100 Chieti, Italy
  • 4. Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, 89073 Ulm, Germany

Description

Obesity is a global health burden for which we do not yet have effective treatments for prevention or therapy.
Plants are an invaluable source of bioactive leads possessing anti-adipogenic potential. Ethnopharmacological
use of Ononis spinosa L. roots (OSR) for treatment of obesity and metabolic disorders requires а scientific
rationale. The current study examined the anti-adipogenic capacity of OSR and its secondary metabolites ononin
(ONON) and maackiain (MACK) in human adipocytes as an in vitro model of obesity. Both ONON and MACK
diminished lipid accumulation during adipocyte differentiation. Molecular docking analysis exposed the potential
interactions between MACK or ONON and target regulatory adipogenic proteins. Furthermore, results
from an RT-qPCR analysis disclosed significant upregulation of AMPK by MACK and ONON treatment. In
addition, ONON increased SIRT1, PI3K and ACC mRNA expression, while MACK notably downregulated CEBPA,
AKT, SREBP1, ACC and ADIPOQ. The protein level of PI3K, C/EBPα, PPARγ and adiponectin was reduced upon
MACK treatment in a concentration-dependent manner. Similarly, ONON suppressed PI3K, PPARγ and adiponectin
protein abundance. Finally, our study provides evidence that ONON exerts anti-adipogenic effect by
upregulation of SIRT1 and inhibition of PI3K, PPARγ and adiponectin, while MACK induced strong inhibitory
effect on adipogenesis via hampering PI3K, PPARγ/C/EBPα signaling and anti-lipogenic effect through downregulation
of SREBP1 and ACC. Even though OSR does not hamper adipogenic differentiation, it could be
exploited as a source of natural leads with anti-adipogenic potential. The multidirectional mechanism of action of
MACK warrant further validation in the context of in vivo obesity models.

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Mladenova et al. 2022 Biomedicine & Pharmacotherapy.pdf

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Additional details

Funding

PlantaSYST – Establishment of a Center of Plant Systems Biology and Biotechnology for the translation of fundamental research into sustainable bio-based technologies in Bulgaria 739582
European Commission