Terminalia arjuna prevents Interleukin-18-induced atherosclerosis via modulation of NF-κB/PPAR-γ-mediated pathway in Apo E-/- mice

Inflammopharmacology. 2018 Apr;26(2):583-598. doi: 10.1007/s10787-017-0357-9. Epub 2017 May 25.


Aim of the study: Terminalia arjuna is a medicinal plant well known as a cardiotonic in Ayurvedic system of medicine. We hypothesized that aqueous stem bark extract of T. arjuna (TAE) may inhibit IL-18-induced atherosclerosis via NF-κB/PPAR-γ-mediated pathway in Apo E-/- mice.

Materials and methods: 12-week-old, male Apo E-/- mice divided into four groups (n = 6/group) fed with normal chow-diet were employed: GP I: phosphate buffer saline (PBS) (2 month); GP II: rIL-18 (1 month) followed by PBS (1 month); GP III: rIL-18 (1 month) followed by TAE (1 month); GP IV: rIL-18 (1 month) followed by atorvastatin (1 month).

Results: IL-18 treatment induced a significant increase (p < 0.001) in pro-inflammatory marker (IL-18) (170 ± 9.16 vs. 1178.66 ± 8.08, pg/ml), and downregulated cholesterol efflux gene (PPAR-γ) by ~0.6-fold vs. 1.00 in IL-18-treated mice as compared to the control animals, respectively. TAE treatment to both groups caused a significant reduction in IL-18 to 281.66 ± 9.60 vs. 1178.66 ± 8.08 (pg/ml), upregulated cholesterol efflux gene by ~1.5- vs. 0.6-fold in TAE-treated group, decreased atherogenic lipids, and percentage atherosclerotic lesion area, demonstrating comparable effects with atorvastatin.

Conclusion: Our data demonstrate that TAE protects against IL-18-induced atherosclerosis via NF-κB/PPAR-γ-mediated pathway.

Keywords: Apo E−/−; Atherosclerosis; LXR-α; NF-κB; PPAR-γ; Recombinant IL-18; Terminalia arjuna.

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Apolipoproteins E / metabolism*
  • Atherosclerosis / drug therapy*
  • Atherosclerosis / metabolism
  • Disease Models, Animal
  • Interleukin-18 / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / metabolism*
  • PPAR gamma / metabolism*
  • Plant Extracts / pharmacology*
  • Plants, Medicinal / chemistry
  • Terminalia / chemistry*


  • Antioxidants
  • Apolipoproteins E
  • Interleukin-18
  • NF-kappa B
  • PPAR gamma
  • Plant Extracts