Allicin, a SUR2 opener: possible mechanism for the treatment of diabetic hypertension in rats

Abstract

Abstract:The garlic (Allium sativum L., Amaryllidaceae) has been popularly used in the treatment of diabetes and cardiac complications. In the present work, we have studied the possible mechanisms, sulfonylurea receptor (SUR) selectivity of allicin in diabetic hypertensive rats. Diabetic hypertension was induced by intraperitoneal injection of streptozotocin (50 mg/kg) followed by daily administration of dexamethasone (10 μg/kg, s.c.). Different parameters, blood pressure and blood glucose levels were studied in the rats weekly up to eight weeks. Allicin (8 mg/ kg, p.o.) shows potent antidiabetic (*p<0.001) as well as antihypertensive effect (**p<0.001, *p<0.01). It may act as a vasodilator by hyperpolarizing the membrane of normal vascular smooth muscle cells. The hyperpolarization in vascular smooth muscle occurs due to K + channel opener activity. Antihypertensive effect of allicin is inhibited by glibenclamide, nonselective SUR blocker while combination of allicin with nateglinide, selective SUR1 blocker exerted synergistic antihypertensive effect. The results indicates that allicin is effective in the treatment of diabetic hypertension; through a mechanism that might involve selective opening of SUR2.

Antihypertensive effect of allicin in dexamethasone-induced hypertensive rats

“… 5 , 6 , 11 , 30 , 31 This report was further supported by the finding that allicin selectively opens SUR2, a type of K + channel receptor, present in blood vessels, leading to dilation of blood vessels, which may be a possible mechanism for the antihypertensive activity of allicin. 32 Other studies have also revealed that fresh garlic extract (allicin) has inhibitory activity against angiotensin 1 converting enzyme and diuretic activity, which may be involved in the antihypertensive action of garlic. 10 , 11 , 12 , 28 , 33 , 34 …”

Mecanismos moleculares de los efectos benéficos de la alicina sobre la enfermedad cardiovascular

“…Sin embargo, actualmente hay varios estudios que continúan utilizando la alicina en distintos grados de pureza y es probable que por ello aún exista controversia respecto a cuál es la dosis o concentración óptima de la alicina capaz de inducir efectos benéficos. A este respecto, la dosis de la alicina reportada para obtener efectos cardioprotectores en modelos experimentales es a dosis tan bajas como 8 mg/kg 44 . En pacientes, las dosis utilizadas para obtener un efecto terapéutico está en un rango más amplio, el cual va de los 10 a los 40 mg/día y no se han documentado o descrito efectos adversos, ni mal olor, tanto en estudios a corto como a largo plazo 24,25,45 .…”

“…Mediante el análisis in silico se concluyó que la alicina actúa en forma similar al losartán (antihipertensivo antagonista del AT1R) 43 . En ratas diabéticas hipertensas, la alicina redujo la hipertensión por un mecanismo que implicó la apertura de un canal de potasio dependiente de trifosfato de adenosina y la participación del receptor de sulfonilurea tipo 2 44 . En pacientes con hipertensión severa, la alicina demostró un efecto antihipertensivo 5 horas después de la administración y con una duración máxima de 5-14 horas 45 .…”

Cellular Mechanisms Underlying the Cardioprotective Role of Allicin on Cardiovascular Diseases

“…In this respect, allicin induces antihypertensive effects in vivo in hypertensive rats, while in vitro showed concentration-dependent and endothelium-dependent vasorelaxant effects in vascular smooth muscle cells, such effects were mediated by the production of H 2 S. Allicin increased the levels of cyclic guanosine monophosphate (cGMP), cyclic adenosine monophosphate (cAMP), and endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxation [ 87 ]. In hypertensive diabetic rats, allicin reduced hyperglycemia and hypertension by a mechanism related to the opening of an ATP-dependent potassium channel (K ATP channel) with the participation of the type 2 sulfonylurea receptor (SUR2) [ 88 ]. On the other hand, in experimental CKD, allicin reduced hypertension, oxidative stress, and improved renal function.…”