The effect of eight weeks of crocetin extract along with aerobic exercise on the expression of VEGF and endothelin-1 gene in heart tissue of elderly diabetic rats

Subject Areas : Role of Genes in Health

shahram pouya ¹ , khosro jalalidehkordi ^{2 *} , Farzaneh Taghian ³ , mehdi kargarfard ⁴ , سید علی حسینی ⁵

1 - Isfahan (Khorasgan) Branch, Islamic Azad University
2 - دانشگاه آزاد اسلامی، واحد اصفهان(خوراسگان)، اصفهان، ایران
3 - Isslamic Azad Isfahan university, sport department
4 - Department of Exercise Physiology, Faculty of Sport Sciences, University of Isfahan, Isfahan, Iran
5 - Islamic Azad University of Iran

Received: 2024-07-12 Accepted : 2025-01-06 Published : 2025-06-21

Keywords: Exercise, crocetin, angiogenesis, heart, elderly, diabetes,

Abstract :

Background and aims: Diabetes is one of the main risk factors for cardiovascular diseases that lead to impaired endothelial function and defective angiogenesis. The purpose of this study is to investigate the effect of eight weeks of consumption of crocetin extract along with aerobic exercise on the expression of VEGF and endothelin-1 gene in the heart tissue of preterm rats. Diabetes and elderly diabetes were performed Methods In this experimental trial, 25 elderly female c57bl6 male mice with diabetes, aged 14-16 weeks and weighing 30-35 grams, were divided into groups (1) diabetic (2) diabetic + aerobic exercise (3) diabetic + crocetin ( 4) Diabetics + aerobic exercise + crocetin and (5) healthy control were divided. Aerobic exercise group did intermittent aerobic exercise for eight weeks, five sessions a week, and 40 mg/kg dose of streptozotocin (STZ) was injected. They also received 30 mg/kg/day crocetin. The expression of VEGF and endothelin 1 genes was measured by Real Time PCR technique. One-way analysis of variance and Tukey's post hoc test were used for data analysis. was (P≥0.05). Results: The expression values of VEGF and endothelin 1 in the diabetes group were significantly higher than other groups (P≥0.05); Conclusion: It seems that interval aerobics and crocetin both alone and simultaneously are effective in improving angiogenesis in diabetic heart tissue. Therefore, it is recommended to use periodic aerobics and crocetin in diabetic conditions of old age

References:

1.Shabab S, Mahmoudabady M, Gholamnezhad Z, Fouladi M, Asghari AA. Diabetic cardiomyopathy in rats was attenuated by endurance exercise through the inhibition of inflammation and apoptosis. Heliyon. 2024 ; 15;10(1). DOI: 10.1016/j.heliyon.2023.e23427

2. Zhang F, Lin JJ, Tian HN, Wang J. Effect of exercise on improving myocardial mitochondrial function in decreasing diabetic cardiomyopathy. Experimental Physiology. 2024 Feb;109(2):190-201. DOI: 10.1113/EP091309 .
3.Seyfi F ,Landi KH, The effect of moderate intensity endurance training on the expression of angiogenesis factors and oxidative stress of the heart in rats. Journal of Ardabil University of Medical Sciences.2020;20(3):361-37 .DOI:1http://jarums.arums.ac.ir/article-1-1953-fa.html [In persion]

4. Daulay ER, Munir D, Lelo A, Putranto TA, Icksan AG, Haryuna TS, Eyanoer PC, Tobing TC. Effect of intra-arterial heparin flushing (IAHF) to prestin and vascular endothelial growth factor (VEGF) level in hearing loss patients. Pharmacia. 2023 ; 31;70(2):351-8. DOI :10.5455/medarh.2023.77.218-221

5. Smeijer JD, Kohan DE, Webb DJ, Dhaun N, Heerspink HJ. Endothelin receptor antagonists for the treatment of diabetic and nondiabetic chronic kidney disease. Current opinion in nephrology and hypertension. 2021; 1;30(4):456-65. DOI: 10.1097/MNH.0000000000000716

6. Dąbek J, Piotrkowicz J, Głogowska-Ligus J, Domagalska-Szopa M, Szopa A, Schreiber L. Expression of the Endothelin-1 Gene and Its Type a Receptor including Physical Activity among Patients with Acute Myocardial Infarction. International Journal of Environmental Research and Public Health. 2022 Jun 14;19(12):7289. DOI: 10.3390/ijerph19127289 .
7.Izadi MR, Aghdasi A, Akbari Neda, Bababegi M. Investigating the effect of high-intensity interval training on cardio-respiratory fitness levels, endothelin-1 and nitric oxide levels in obese people. Journal of Jiroft University of Medical Sciences.2020;9(4);789-798. DOI:
8.Kon, M., Ebi, Y., & Nakagaki, K. . Effects of a single bout of high-intensity interval exercise on C1q/TNF-related proteins. Applied physiology, nutrition, and metabolism.2019; 44(1), 47-51. DOI:10.1139/apnm-2018-0355
9. Kazemi Pordanjani M, Banitalebi E, Roghani M, Hemmati R. Ursolic acid enhances the effect of exercise training on vascular aging by reducing oxidative stress in aged type 2 diabetic rats. Food Science & Nutrition. 2023;11(2):696-708. DOI: 10.1002/fsn3.3105
10. Shabab S, Mahmoudabady M, Gholamnezhad Z, Niazmand S, Fouladi M, Emadi ZM. Endurance Exercise Prevented Diabetic Cardiomyopathy through the Inhibition of Fibrosis and Hypertrophy in Rats. Reviews in Cardiovascular Medicine. 2024 ; 16;25(5):173. DOI:10.31083/j.rcm2505173
11.Su X, Yuan C, Wang L, Chen R, Li X, Zhang Y, et al. The beneficial effects of saffron extract on potential oxidative stress in cardiovascular diseases. Oxidative Medicine and Cellular Longevity 2021; 19: 1-14. DOI:10.1155/2021/6699821

12. G Gutheil W, Reed G, Ray A, Anant S, Dhar A. Crocetin: an agent derived from saffron for prevention and therapy for cancer. Current Pharmaceutical Biotechnology 2012; 13(1): 173. DOI: 10.2174/138920112798868566 .

13.Miladjerdi A, Haghighatdost F, Azadbakh L. Toxicity of saffron, crocin and its crostin against cancer and normal cells: a systematic review. Clinical excellence.2015;4(1);33-53 DOI: http://ce.mazums.ac.ir/article-۱-۸۰۰-fa.html.


14.Moghadasi M, Akbari F, Najafi P. Interaction of aerobic exercise and crocin improves memory, learning and hypocampic tau and neurotrophins gene expression in rats treated with trimethytin as a model of Alzheimer’s disease. Molecular biology reports. 2024;51(1):111. DOI: 10.1007/s11033-023-09197-4

15. Haghparast Azad M, Niktab I, Dastjerdi S, Abedpoor N, Rahimi G, Safaeinejad Z, et al. The combination of endurance exercise and SGTC (Salvia–Ginseng–Trigonella–Cinnamon) ameliorate mitochondrial markers’ overexpression with sufficient ATP production in the skeletal muscle of mice fed AGEs-rich high-fat diet. Nutrition & metabolism. 2022; 5;19(1):17. DOI:10.1186/s12986-022-00652-w
16. Zhang J, Wang Y, Dong X, Liu J. Crocetin attenuates inflammation and amyloid-β accumulation in APPsw transgenic mice. Immunity & Ageing. 2018;15(1):1-8. DOI: 10.1186/s12979-018-0132-9
17. Soori R, CHoobine S. Effect of endurance training on VEGF protein level in tissue of cardiac muscle in STZ-induced diabetic Wistar rats. Yafteh 2018; 20: 110-24. DOI:.org/10.29252/aassjournal.7.1.11
18. Izadi MR, Afousi AG, Fard MA, Bigi MAB. High-intensity interval training lowers bloodpressure and improves apelin and NOx plasma levels in older treated hypertensive individuals. Journal of Physiology and Biochemistry. 2018;74(1):47-55 DOI: 10.1007/s13105-017-0602-0.
19.Monazami AM,Etemad Z,Nazari A,Mohamadi M. The effect of eight weeks of endurance training combined with the consumption of cinnamon stick extract on the expression of angiogenic markers in the heart tissue of streptotocin treated diabetic male rats. Physiology of exercise and physical activity journal.2022;5(1);11-20. DOI: 10.52547/joeppa.15.1.11
20.Rajabi A, Seyahkohian M,Akbarnejad A. Comparison of the effect of a therapeutic exercise program and oral consumption of saffron on the levels of IL-6, TNF-a and glycemic control in obese women with type 2 diabetes.2015,25(66);20-33. DOI: file:///C:/Users/JLL-101/Downloads/524139716603.pdf

21.Kohpayeh Z,Farsi S, Hoseyni A,Fathi E. The effect of continuous and intermittent exercise training with crocin consumption on the expression of AP-1 and NF-κB genes in heart tissue of obese male Wistar rats. Applied sports physiology research paper.2021;17(33);161-171 DOI: https://asp.journals.umz.ac.ir/article_3364_0bd5a69e23fbf938f2895e1d53502873.pdf

22.Reynolds LJ, Credeur DP, Manrique C, Padilla J, Fadel PJ, Thyfault JP. Obesity, type 2 diabetes, andimpaired insulin-stimulated blood flow: role of skeletal muscle NO synthase and endothelin-1. Journal of applied physiology. 2017; 122(1):38-47 DOI: 10.1152/japplphysiol.00286.2016 .


. 23.Kostov K, Blazhev A, Atanasova M, Dimitrova A. Serum concentrations of endothelin-1 and matrix metalloproteinases-2,-9 in pre-hypertensive and hypertensive patients with type 2 diabetes. International journal of molecular sciences. 2016,1182 . DOI: 10.3390/ijms17081182

24.Zanatta CM, Gerchman F, Burttet L, Nabinger G, Jacques-Silva MC, Canani LH, et al. Endothelin-1levels and albuminuria in patients with type 2diabetes mellitus. Diabetes research and clinical practice. 2008; 80(2):299-304. DOI: 10.1016/j.diabres.2007.12.024
25. Campia U, Tesauro M, Di Daniele N, Cardillo C. The vascular endothelin system in obesity and type 2diabetes: Pathophysiology and therapeutic implications. Life sciences. 2014; 118(2):149-55 . DOI: 10.1016/j.lfs.2014.02.028

26.Zarei M, Beheshti Nasr SMB, Hamedinia M, Taheri Chadorneshin H, Askari Majdabadi H. Effects of 12 weeks of combined aerobic-resistance exercise training on levels of chemerin, omentin and insulin resistance in men with type 2 diabetes. Koomesh. 2020; 22(1):155-63 DOI: http://koomeshjournal.semums.ac.ir/browse.php?a_code=A-10-161-1&sid=1&slc_lang=en