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Partial Synthetic PPARƳ Derivative Ameliorates Aorta Injury in Experimental Diabetic Rats Mediated by Activation of miR-126-5p Pi3k/AKT/PDK 1/mTOR Expression

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Department of Pharmacology and Toxicology, Faculty of Pharmacy, Nahda University, Beni-Suef 62521, Egypt
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Department of Pharmacognosy, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia
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Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Nahda University, Beni-Suef 62521, Egypt
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Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62521, Egypt
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Department of Pharmacognosy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62521, Egypt
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School of Computing, Engineering & Physical Sciences, University of the West of Scotland, Paisley PA1 2BE, UK
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Authors to whom correspondence should be addressed.
Academic Editor: Seong-Hee Maria Ko
Pharmaceuticals 2022, 15(10), 1175; https://doi.org/10.3390/ph15101175
Received: 30 August 2022 / Revised: 17 September 2022 / Accepted: 17 September 2022 / Published: 22 September 2022
(This article belongs to the Special Issue Drug Candidates for the Treatment of Metabolic Syndrome)
Type 2 diabetes mellitus (T2D) is a world wild health care issue marked by insulin resistance, a risk factor for the metabolic disorder that exaggerates endothelial dysfunction, increasing the risk of cardiovascular complications. Peroxisome proliferator-activated receptor PPAR) agonists have therapeutically mitigated hyperlipidemia and hyperglycemia in T2D patients. Therefore, we aimed to experimentally investigate the efficacy of newly designed synthetic PPARα/Ƴ partial agonists on a High-Fat Diet (HFD)/streptozotocin (STZ)-induced T2D. Female Wistar rats (200 ± 25 g body weight) were divided into four groups. The experimental groups were fed the HFD for three consecutive weeks before STZ injection (45 mg/kg/i.p) to induce T2D. Standard reference PPARƳ agonist pioglitazone and the partial synthetic PPARƳ (PIO; 20 mg/kg/BW, orally) were administered orally for 2 weeks after 72 h of STZ injection. The aorta tissue was isolated for biological ELISA, qRT-PCR, and Western blotting investigations for vascular inflammatory endothelial mediators endothelin-1 (ET-1), intracellular adhesion molecule 1 (ICAM-1), E-selectin, and anti-inflammatory vasoactive intestinal polypeptide (VIP), as well as microRNA126-5p and p-AKT/p-Pi3k/p-PDK-1/p-mTOR, endothelial Nitric Oxide Synthase (eNOS) immunohistochemical staining all are coupled with and histopathological examination. Our results revealed that HFD/STZ-induced T2D increased fasting blood glucose, ET-1, ICAM-1, E-selectin, and VIP levels, while decreasing the expression of both microRNA126-5p and p-AKT/p-Pi3k/p-PDK-1/p-mTOR phosphorylation. In contrast, the partial synthetic PPARƳ derivative evidenced a vascular alteration significantly more than reference PIO via decreasing (ET-1), ICAM-1, E-selectin, and VIP, along with increased expression of microRNA126-5p and p-AKT/p-Pi3k/p-PDK-1/p-mTOR. In conclusion, the partial synthetic PPARƳ derivative significantly affected HFD/STZ-induced T2D with vascular complications in the rat aorta. View Full-Text
Keywords: type 2 diabetes mellitus (T2D); peroxisome proliferator-activated receptor (PPAR); intracellular adhesion molecule 1 (ICAM-1); endothelial nitric oxide synthase (eNOS); endothelin-1 (ET-1) type 2 diabetes mellitus (T2D); peroxisome proliferator-activated receptor (PPAR); intracellular adhesion molecule 1 (ICAM-1); endothelial nitric oxide synthase (eNOS); endothelin-1 (ET-1)
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MDPI and ACS Style

Ahmed, Y.M.; Orfali, R.; Abdelwahab, N.S.; Hassan, H.M.; Rateb, M.E.; AboulMagd, A.M. Partial Synthetic PPARƳ Derivative Ameliorates Aorta Injury in Experimental Diabetic Rats Mediated by Activation of miR-126-5p Pi3k/AKT/PDK 1/mTOR Expression. Pharmaceuticals 2022, 15, 1175. https://doi.org/10.3390/ph15101175

AMA Style

Ahmed YM, Orfali R, Abdelwahab NS, Hassan HM, Rateb ME, AboulMagd AM. Partial Synthetic PPARƳ Derivative Ameliorates Aorta Injury in Experimental Diabetic Rats Mediated by Activation of miR-126-5p Pi3k/AKT/PDK 1/mTOR Expression. Pharmaceuticals. 2022; 15(10):1175. https://doi.org/10.3390/ph15101175

Chicago/Turabian Style

Ahmed, Yasmin M., Raha Orfali, Nada S. Abdelwahab, Hossam M. Hassan, Mostafa E. Rateb, and Asmaa M. AboulMagd. 2022. "Partial Synthetic PPARƳ Derivative Ameliorates Aorta Injury in Experimental Diabetic Rats Mediated by Activation of miR-126-5p Pi3k/AKT/PDK 1/mTOR Expression" Pharmaceuticals 15, no. 10: 1175. https://doi.org/10.3390/ph15101175

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