Kaempferol protects against streptozotocin-induced diabetic cardiomyopathy in rats by a hypoglycemic effect and upregulating SIRT1
Affiliations
Affiliations
- Biology Department, College of Science, King Khalid University, Abha, Saudi Arabia.
- Biology Department, College of Science, King Khalid University, Abha, Saudi Arabia. elkottaf@yahoo.com; elkottaf@sci.dmu.edu.eg; elkottaf@kku.edu.sa.
- Zoology Department, College of Science, Damanhour University, Damanhour, Egypt.
- Applied Medical Sciences Department, College of Health Sciences, PAAET, Safat, Kuwait.
- Pathology Department, College of Medicine, Taif University, Taif, Saudi Arabia.
- Biology Department, College of Science, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.
- Pharmaceutical Sciences Department, Pharmacy Program, Batterjee Medical College, Jeddah, Saudi Arabia.
- Pharmacology Department, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, Egypt.
Abstract
This study investigated if kaempferol could attenuate the oxidative, inflammatory, and fibrotic damage of the left ventricles (LVs) in streptozotocin (STZ)-diabetic rats by modulating silent mating type information regulation 2 homolog 1 (SIRT1) signaling. Adult male rats were divided into 5 groups (n = 12/each) as control, control + kaempferol, STZ-induced diabetes mellitus (STZ-DM), STZ-DM + kaempferol, and STZ-DM + kaempferol + EX-527, a sirtuin 1 (SIRT1) inhibitor. Administration of kaempferol to diabetic rats significantly preserved the systolic and diastolic functions of the LVs that was associated with a significant reduction in ventricular collagen deposition, infiltration of inflammatory cells, and protein expression of Bcl2-associated X protein (Bax), cleaved caspase-3, and cytochrome-C. In both the control and diabetic rats, kaempferol attenuated the loss in body weights, reduced fasting glucose levels, and increased fasting insulin levels and HOMA-β. Besides, kaempferol lowered the levels of reactive oxygen species (ROS), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6), downregulated the transforming growth factor-β1 (TGF-β1) and reduced the nuclear levels of NF-κB p65. In concomitant, kaempferol increased the LV levels of manganese superoxide dismutase (MnSOD) and glutathione (GSH) and stimulated the total protein levels of Bcl2, the nuclear activity of SIRT1, and nuclear levels of nuclear factor erythroid 2-related factor 2 (Nrf2). These events were associated with increased deacetylase activity and total levels of SIRT1 and a parallel decrease in the acetylation of Nrf2, NF-κB, smad2, and FOXO1. In conclusion: kaempferol attenuate diabetic cardiomyopathy in STZ-treated rats through its hypoglycaemic and insulin-releasing effects, as well as a cardiac independent mechanism that involves activation of SIRT1.
Similar articles
Altamimi JZ, Alfaris NA, Alshammari GM, Alagal RI, Aljabryn DH, Aldera H, Alkhateeb MA, Yahya MA.J Physiol Pharmacol. 2020 Dec;71(6). doi: 10.26402/jpp.2020.6.12. Epub 2021 Apr 22.PMID: 33901999
Urolithin A prevents streptozotocin-induced diabetic cardiomyopathy in rats by activating SIRT1.
Albasher G, Alkahtani S, Al-Harbi LN.Saudi J Biol Sci. 2022 Feb;29(2):1210-1220. doi: 10.1016/j.sjbs.2021.09.045. Epub 2021 Sep 17.PMID: 35241966 Free PMC article.
Al Sabaani N.J Ocul Pharmacol Ther. 2020 Sep;36(7):563-577. doi: 10.1089/jop.2019.0151. Epub 2020 May 15.PMID: 32412821
Tang G, Li S, Zhang C, Chen H, Wang N, Feng Y.Acta Pharm Sin B. 2021 Sep;11(9):2749-2767. doi: 10.1016/j.apsb.2020.12.020. Epub 2021 Feb 2.PMID: 34589395 Free PMC article. Review.
Hussain Y, Khan H, Alsharif KF, Hayat Khan A, Aschner M, Saso L.Molecules. 2022 Jun 28;27(13):4145. doi: 10.3390/molecules27134145.PMID: 35807387 Free PMC article. Review.
Cited by
Liu H, Meng W, Zhao D, Ma Z, Zhang W, Chen Z, Li Z, Zhao P.Front Pharmacol. 2023 Jan 11;13:1074286. doi: 10.3389/fphar.2022.1074286. eCollection 2022.PMID: 36712682 Free PMC article.
Jia L, Jing Y, Wang D, Cheng S, Fu C, Chu X, Yang C, Jiang B, Xin S.Front Physiol. 2022 Oct 20;13:1034014. doi: 10.3389/fphys.2022.1034014. eCollection 2022.PMID: 36338468 Free PMC article.
Mechanisms of Kaempferol in the treatment of diabetes: A comprehensive and latest review.
Yang Y, Chen Z, Zhao X, Xie H, Du L, Gao H, Xie C.Front Endocrinol (Lausanne). 2022 Sep 7;13:990299. doi: 10.3389/fendo.2022.990299. eCollection 2022.PMID: 36157449 Free PMC article. Review.
Cardiac Acetylation in Metabolic Diseases.
Dubois-Deruy E, El Masri Y, Turkieh A, Amouyel P, Pinet F, Annicotte JS.Biomedicines. 2022 Jul 29;10(8):1834. doi: 10.3390/biomedicines10081834.PMID: 36009379 Free PMC article. Review.
Ma Y, Liu J, Cui X, Hou J, Yu F, Wang J, Wang X, Chen C, Tong L.Molecules. 2022 Jul 17;27(14):4553. doi: 10.3390/molecules27144553.PMID: 35889427 Free PMC article.