ABSTRACT
Addiction and withdrawal are problems disturbing the health of the individual and also causes difficulties for society, raising the rates of divorce, unemployment and government spending on legal and medical systems. Opioids show an important pharmacological effect in the treatment of pain, with extremely addictive potential. Chronic opioid exposure is known to produce the complex behaviors of tolerance and dependence, a state exposed by opioid abstinence leading to withdrawal syndrome, as well as oxidative stress. Studies show that calcium mediated secondary messengers play a crucial role in the mechanism of addictive process and oxidative stress induced by chronic opioid usage. Calcium/calmodulin-dependent protein kinase II (CaMKII), is a major calcium regulated signal transducer that controls many neuronal systems and play important role in neuronal plasticity and can act as a key and direct promoting opioid tolerance and dependence and identifying such a direct mechanism may be useful for designing a pharmacology treatment for these conditions, recent studies, has been shown that calcium channels antagonist can be used in the treatment of withdrawal syndrome. Chronic opioid exposure associated with tolerance, dependence withdrawal syndrome and oxidative stress. Studies has shown that calcium mediated secondary messengers involved in the genesis of these conditions, better understanding of biological mechanisms underlie reduction in neuronal cell excitability could help in the identification of pharmacological targets for treatment.
ABSTRACT
The study was to evaluate the most effective fraction and subfraction having hypoglycemic activity from the hydro-methanolic (2:3) extract of the fruit of Persea americana Mil. through bioactivity guided investigation in streptozotocin induced diabetic rats. Out of different solvent fractions and subfractions, the effective fraction and subfraction of Persea americana Mill. were subjected to antidiabetic study in streptozotocin-induced diabetic rat. Serum insulin, glycosylated hemoglobin, transaminases, carbohydrate metabolic enzymes in liver, kidney, cardiac and skeletal muscle, were also assessed after 8 weeks of treatment and compared to the vehicle control. A significant recovery was noted in the level of serum insulin, glycosylated hemoglobin, activities of carbohydrate metabolic enzymes and serum transaminases after n-hexane fraction treatment in respect with other treated groups. Two sub fractions A and B were obtained using petroleum ether sub fractionation of which sub fraction B was more bioactive considering the above biosensors and was comparable with glibenclamide. HPTLC study focused four and two components (P1 and P2) in sub fraction A and B respectively where P1 is major, confirmed by HPLC study. The dose of sub fraction B was 1/4th of the n-hexane fractions dose. It has been concluded that sub fraction B (P1 and P2) which was obtained from nhexane fraction had the antidiabetic activities in the streptozotocin-induced diabetic model.