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.
ABSTRACT
Pulsatile drug delivery systems are developed to deliver drug according to circadian behavior of diseases. This means that these systems will deliver drug at time when disease display it’s most morbid and mortal state within a circadian cycle (24 hrs.). The product follow a sigmoidal drug release profile characterized by a time period of no release (lag time) followed by a rapid and complete drug release. Thus drug can be delivered at right time, in right amount and at right site of action by use of such approach. The potential benefits of chronotherapeutics have been investigated and established for number of diseases like asthma, arthritis, cancer, diabetes, epilepsy, hypertension, ulcer, hypercholesterolemia etc. Various capsular, osmotic, single and multiple unit systems that are modulated by soluble or erodible polymer coatings, rupturable membranes are available in market. These systems are beneficial for diseases showing chronopharmacological behavior where night time dosing is required or for the drugs having high first pass effect or having site specific absorption in GIT, or for drugs with high risk of toxicity or tolerance. These systems also improve patient compliance by decreasing dosing frequency.