Plants (Nov 2022)

Hydroethanolic Extract of <i>Morus nigra</i> L. Leaves: A Dual PPAR-α/γ Agonist with Anti-Inflammatory Properties in Lipopolysaccharide-Stimulated RAW 264.7

  • Amanda de Assis Carneiro,
  • Simone Batista Pires Sinoti,
  • Marcela Medeiros de Freitas,
  • Luiz Alberto Simeoni,
  • Christopher William Fagg,
  • Pérola de Oliveira Magalhães,
  • Dâmaris Silveira,
  • Yris Maria Fonseca-Bazzo

DOI
https://doi.org/10.3390/plants11223147
Journal volume & issue
Vol. 11, no. 22
p. 3147

Abstract

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Inhibition of systemic inflammation has been a beneficial strategy in treating several non-communicable diseases, which represent one of the major causes of mortality in the world. The Peroxisome Proliferator-Activated Receptors (PPAR) are interesting pharmacological targets, since they can act both through the metabolic and anti-inflammatory pathways. Morus nigra L. has flavonoids in its chemical composition with recognized anti-oxidant activity and often associated with anti-inflammatory activity. Therefore, this study aimed to evaluate the hydroethanolic extract of M. nigra leaves’ ability to activate PPAR and promote anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated murine macrophage cells. The leaf extract was prepared by cold maceration, and the chemical profile was obtained by HPLC-DAD. Activation of PPAR α and γ was evaluated by the luciferase reporter assay. The anti-inflammatory activity was assessed by measuring the reactive oxygen species (ROS), nitric oxide (NO), and Tumor Necrosis Factor-α (TNF-α) in RAW 264.7 cells after stimulation with LPS from Escherichia coli. The HPLC-DAD analysis identified two major compounds: rutin and isoquercitrin. The extract showed agonist activity for the two types of PPAR, α and γ, although its major compounds, rutin and isoquercitrin, did not significantly activate the receptors. In addition, the extract significantly reduced the production of ROS, NO, and TNF-α. Treatment with the specific PPAR-α antagonist, GW 6471, was able to partially block the anti-inflammatory effect caused by the extract.

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