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

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Abstract

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.

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Acknowledgements

We thank Dr. B. Sesikeran for providing facilities at the National Institute of Nutrition, Hyderabad to carry out the research work on Apo E−/− mice.

Source of funding

We thank the Department of Biotechnology, New Delhi, India, for providing the financial support.

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Authors and Affiliations

  1. Department of Pharmcology and Toxicology, Virginia Commonwealth University, Richmond, VA, USA

    Owais Mohammad Bhat & Ashfaq Ahmad

  2. National Centre for Laboratory Animal Sciences (NCLAS), National Institute of Nutrition (NIN), Hyderabad, India

    K. Rajender Rao

  3. Department of Histopathology, National Institute of Nutrition (NIN), Hyderabad, India

    P. Uday Kumar

  4. Department of Experimental Medicine and Biotechnology, Research Block-B, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, 160012, India

    Veena Dhawan

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  1. Owais Mohammad Bhat
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Correspondence to Veena Dhawan.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The animal protocol was approved by the Institute Animal Ethics Committee (IAEC) (reference No. 49/IAEC/237) of PGIMER, Chandigarh. All the animal procedures were performed following the US National Institutes of Health protocol.

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Bhat, O.M., Kumar, P.U., Rao, K.R. et al. Terminalia arjuna prevents Interleukin-18-induced atherosclerosis via modulation of NF-κB/PPAR-γ-mediated pathway in Apo E−/− mice. Inflammopharmacol 26, 583–598 (2018). https://doi.org/10.1007/s10787-017-0357-9

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