Diabetes mellitus is a serious global health problem and taking its place as one of the main threats to human health in the 21 st century. The National Diabetes Information Clearinghouse & World Health Organization shows above 90% of the diabetic population fall under type 2 diabetes mellitus category. The treatment generally prescribed for type 2 diabetes mellitus has been a combination of diet, exercise and current therapeutic agents Due to their adverse effects and side effects, most of these treatments are considered to be unsatisfactory in terms of preventio n of complications and preservation of quality of life. The current therapeutic agents containing thiazolidine-2,4-diones or glitazones are shown better treatment on type 2 diabetes mellitus via acting on peroxisome proliferator-activated receptor-gamma (PPAR-γ). From these glitazones, troglitazone and rosiglitazone are withdrawn from markets. Pioglitazone and lobeglitazone are used in market. Ciglitazone, englitazone, darglitazone, KRP-297, rivoglitazone and CLX-921 are discontinued in various clinical trials. Mitoglitazone, netoglitazone and balaglitazone are present in various phases of clinical trials. Furthermore, based on various literature surveys, we are studied in details structure activity relationships of various glitazones.
Objective: Linagliptin, an anti-diabetic agent, proven to play an important role in regulating neuronal plasticity and reduce apoptosis and neuroinflammation by activating downstream AMPK/Sirt 1 pathway, which protects mitochondrial function and suppresses intracellular ROS accumulation and shows antioxidant action. Celiprolol, a β-1selective adrenoceptor blocker used as an anti-hypertensive agent, possesses a direct scavenging activity on oxygen radicals with antioxidant properties. The current study was designed to investigate the combined neuroprotective effect of linagliptin and celiprolol. Methods: Wistar rats of either sex were divided into different groups (n = 6). Eight groups each for Reserpine induced orofacial dyskinesia model and Rotenone induced neurodegeneration model to mimic Parkinson’s like conditions and treated or not with different doses of linagliptin and celiprolol. 24 h after the last dose, animals were subjected to behavioral, biochemical and histopathological evaluations. The data were analyzed by ANOVA and Bonferroni multiple comparison test. Results: Reserpine treatment increased VCMs, tongue protrusion and decreased locomotor activity. Rotenone treatment decreases the motor activity and exploratory ability of the animals. Reserpine as well as rotenone treatments decrease catalase, GSH, SOD and increase the LPO levels as compared to sham group animals. Reserpine and rotenone also showed the presence of ghost cells and vacuolated cytoplasm. Linagliptin and celiprolol alone as well as in combination normalized the behavioral, biochemical and histopathological complications. Conclusion: Linagliptin and Celiprolol showed neuroprotection by antioxidant activity as well as improved reserpine and rotenone-induced behavioral deficits. Both drugs have tenacious potential and can be used clinically with some further investigations.
Type 2 diabetes mellitus and its complications, decreases the quality of life in diabetic patients. Thiazolidine-2,4-diones are found to be better insulin sensitizing agents, acting on peroxisome proliferator activated receptor-γ (PPAR-γ) and decrease blood glucose level in diabetic patient. Therefore, in the present work, we synthesized 5-[4-(substituted) sulphonylbenzylidene]thiazolidine-2,4-diones and evaluated for their oral hypoglycemic activity. The synthesized compounds were further studied for their find out interactions with 2PRG protein with the help of docking score and also find out their predicated ED25 values. The results of synthesized compounds were showed significant decrease in blood glucose level as compared to positive control group. All synthesized compounds have shown good hydrogen bond interactions with 2PRG protein, docking score and predicted ED25 value as compared with reference drug, pioglitazone and rosiglitazone, respectively. Thus, sulphonyl linked thiazolidine-2,4-diones may be used as promising oral hypoglycemic agent.
Background: Angiotensin receptor blockers are the new class of compounds used for the treatment of fibrotic diseases. Objectives: The purpose of this study was to investigate cardioprotective effect of irbesartan in isoproterenol induced endoplasmic reticulum stress, which results in myocardial fibrosis. Materials and Methods: Thirty wistar rats were assigned to study, 6 rats in a group. Myocardial fibrosis was induced by isoproterenol (5 mg/kg, s.c. for 15 days) which can cause cardiac toxicity. Irbesartan (10, 20 and 30 mg/kg, p.o.) was administered for 15 days after administration of isoproterenol. Post-treatment with irbesartan, cardiac functional measurements and the left and right ventricular weight indices were analyzed. Pathological alteration of levels of soluble collagen was determined. Results: The administration of irbesartan resulted in a significant (p<0.01) improvement in cardiac function and reduced levels of soluble collagen. Irbesartan also showed decrease in the level of malondialdehyde and an increase in defensive antioxidant enzymes (SOD, CAT, and GSH) thus, exerts antioxidant activity. Conclusion: Irbesartan possesses anti-fibrotic activity and offers protection against myocardial fibrosis, due to regulation of angiotensin II activity through blockade of AT 1 receptors which might attenuate the endoplasmic reticulum stress and thus inhibit myocardial fibrosis via inhibition of oxidative stress. The regulation of antioxidant defensive enzymes may be involved in anti-fibrotic effect of irbesartan.
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