NORMAL VASCULAR REACTIVITY IS RESTORED BY APIGENIN IN DIABETIC RATS
Keywords:Apigenin, Diabetes, PMA, Isolated aorta, Vascular reactivity
Objective: Diabetes is a disease whose complications have serious implications for the health of sufferers; one of the most serious such complications is the deterioration of vascular reactivity. Apigenin is a natural flavonoid with PKC inhibiting and antioxidant properties. In this study, the impact of apigenin on vascular reactivity deterioration was investigated.
Methods: Insulin resistance (IR) and insulin deficiency (ID) were induced by fructose and streptozotocin respectively. The isolated aortae vasoconstriction response to phenylephrine (PE) and potassium chloride (KCl) in addition to the vasodilation response to acetylcholine (ACh) and sodium nitroprusside (SNP) were tested.
Results: IR and ID were associated with significantly exaggerated vasoconstriction to KCl and PE while significantly impaired vasodilation to ACh. Response to SNP was not significantly affected by both IR and ID. In vitro incubation with apigenin (7 7ÂµM) for 20 min restored normal responses to PE, KCl and ACh in aortae isolated from insulin-resistant or insulin-deficient rats. Incubation for one hour with the PKC stimulant, phorbol 12-myristate 13-acetate (PMA, 800 nM) resulted in aortic impairment similar to that seen in aortae isolated from IR and ID animals. Incubation with both apigenin prevented PMA-induced exaggerated vasoconstriction response to both PE and KCl.
Conclusion: Apigenin alleviates vascular exaggerated vasoconstriction and impaired dilation associated with diabetes or PKC activated.
Arafat M, A Salam, O Arafat. The association of type 2 diabetes with obesity and other factors: in the multinational community. Int J Pharm Pharm Sci 2014;6:257-60.
Donnelly R, X Qu. Mechanisms of insulin resistance and new pharmacological approaches to metabolism and diabetic complications. Clin Exp Pharmacol Physiol 1998;25:79-87.
Busija DW. Adverse effects of reactive oxygen species on vascular reactivity in insulin resistance. Antioxid Redox Signal 2006;8:1131-40.
Altan VM. The pharmacology of diabetic complications. Curr Med Chem 2003;10:1317-27.
Akbari CM, FW LoGerfo. Diabetes and peripheral vascular disease. J Vasc Surg 1999;30:373-84.
Madunic J. Apigenin: a dietary flavonoid with diverse anticancer properties. Cancer Lett 2018;413:11-22.
Lin JK. Suppression of protein kinase C and nuclear oncogene expression as possible molecular mechanisms of cancer chemoprevention by apigenin and curcumin. J Cell Biochem Suppl 1997;28-29:39-48.
Lestari D, EY Sukandar, I Fidrianny. In silico study of apigenin and apigetrin as an inhibitor of 3-hydroxy-3-methyl-glutayl-coenzyme a reductase. Asian J Pharm Clin Res 2017;10:4.
Zhu ZY. Apigenin ameliorates hypertension-induced cardiac hypertrophy and down-regulates cardiac hypoxia-inducible factor-lalpha in rats. Food Funct 2016;7:1992-8.
Jiang HD. Endothelium-dependent and direct relaxation induced by ethyl acetate extract from flos chrysanthemi in rat thoracic aorta. J Ethnopharmacol 2005;101:221-6.
Zhang YH. Endothelium-dependent vasorelaxant and anti-proliferative effects of apigenin. Gen Pharmacol 2000; 35: 341-7.
Abdallah HM. Phenolics from garcinia mangostana alleviate exaggerated vasoconstriction in metabolic syndrome through direct vasodilatation and nitric oxide generation. BMC Complementary Altern Med 2016;16:359.
El-Bassossy H. Ferulic acid, a natural polyphenol, alleviates insulin resistance and hypertension in fructose-fed rats: effect on endothelial-dependent relaxation. Chem Biol Interact 2016;254:191-7.
El-Bassossy HM, SM Abo-Warda, A Fahmy. Rosiglitazone, a peroxisome proliferator-activated receptor gamma stimulant, abrogates diabetes-evoked hypertension by rectifying abnormalities in vascular reactivity. Clin Exp Pharmacol Physiol 2012;39:643-9.
El-Bassossy HM, SM Abo-Warda, A Fahmy. Chrysin and luteolin attenuate diabetes-induced impairment in endothelial-dependent relaxation: effect on lipid profile, AGEs and NO generation. Phytother Res 2013;27:1678-84.
El-Bassossy HM. Arginase inhibition alleviates hypertension in the metabolic syndrome. Br J Pharmacol 2013;169:693-703.
El-Bassossy HM, HA Shaltout. Allopurinol alleviates hypertension and proteinuria in high fructose, high salt and high fat-induced model of metabolic syndrome. Transl Res 2015;165:621-30.
Ghareib SA. 6-Gingerol alleviates exaggerated vasoconstriction in diabetic rat aorta through direct vasodilation and nitric oxide generation. Drug Des Dev Ther 2015;9:6019-26.
Hu N. Opposite effect of diabetes mellitus induced by streptozotocin on the oral and intravenous pharmacokinetics of verapamil in rats. Drug Metab Dispos 2011;39:419-25.
Dai S, JH McNeill. Fructose-induced hypertension in rats is concentration-and duration-dependent. J Pharmacol Toxicol Methods 1995;33:101-7.
Xavier FE. Time-dependent hyperreactivity to phenylephrine in aorta from untreated diabetic rats: the role of prostanoids and calcium mobilization. Vascul Pharmacol 2003;40:67-76.
Baluchnejadmojarad T. Beneficial effect of aqueous garlic extract on the vascular reactivity of streptozotocin-diabetic rats. J Ethnopharmacol 2003;85:139-44.
Iyer SN, MJ Katovich. Vascular reactivity to phenylephrine and angiotensin II in hypertensive rats associated with insulin resistance. Clin Exp Hypertens 1996;18:227-42.
Takagawa Y. Long-term fructose feeding impairs vascular relaxation in rat mesenteric arteries. Am J Hypertens 2001;14:811-7.
Carmassi F. Insulin resistance causes impaired vasodilation and hypofibrinolysis in young women with polycystic ovary syndrome. Thromb Res 2005;116:207-14.
Morgan JP, KG Morgan. Calcium and cardiovascular function. Intracellular calcium levels during contraction and relaxation of mammalian cardiac and vascular smooth muscle as detected with aequorin. Am J Med 1984;77:33-46.
El-Bassossy HM. Haem oxygenase-1 induction protects against tumour necrosis factor alpha impairment of endothelial-dependent relaxation in rat isolated pulmonary artery. Br J Pharmacol 2009;158:1527-35.