NLRP3 inflammasome drives inflammation in high fructose fed diabetic rat liver: Effect of resveratrol and metformin.

Aims: To unravel the underlying mechanism of hepatic inflammation during type 2 diabetes (T2DM), we established the diabetic rat model by feeding with high fructose diet for twenty weeks and studied the involvement of inflammasome in the liver of these rats.

Materials And Methods: Male SD rats weighing 180-200 g were divided in four groups: 1) Control (Con group) rats were fed with corn starch diet, 2) diabetic (Dia group) rats were fed with 65% of fructose, 3) diabetic along with resveratrol (10 mg/kg/day); p.o.

SIRT-3 Modulation by Resveratrol Improves Mitochondrial Oxidative Phosphorylation in Diabetic Heart through Deacetylation of TFAM.

Background And Purpose: Mitochondrial dysfunction remains the crucial cause for many heart diseases including diabetic cardiomyopathy (DCM). Sirtuin-3 (SIRT-3) is a protein deacetylase localized in the mitochondria and regulates mitochondrial function. Being a noteworthy mitochondrial protein deacetylase enzyme, the role of SIRT-3 in DCM is yet to be explored.

Potent ACE inhibitors from 5-hydroxy indanone derivatives.

A novel triazole derivatives(±)-2-(hydroxymethyl)-7,8-dihydro-1H-indeno[5,4-b]furan-6(2H)-one (12a-j) were designed and synthesized by the reaction between racemic azide and terminal acetylenes under click chemistry reaction conditions followed by biological evaluation as angiotensin converting enzyme (ACE) inhibitors. β-Amino alcohol derivatives of 1-indanone (15a-l) were synthesized from 5-hydroxy indanone, it was reacted with epichlorohydrin and followed by oxirane ring opening with various piperazine derivatives. Among the newly synthesized compounds 12b (IC: 1.

Toll-Like Receptor 4 Inhibition Improves Oxidative Stress and Mitochondrial Health in Isoproterenol-Induced Cardiac Hypertrophy in Rats.

Background: Inflammation remains a crucial factor for progression of cardiac diseases and cardiac hypertrophy remains an important cause of cardiac failure over all age groups. As a key regulator of inflammation, toll-like receptor 4 (TLR4) plays an important role in pathogenesis of cardiac diseases. Being an important regulator of innate immunity, the precise pathway of TLR4-mediated cardiac complications is yet to be established.

Garlic activates SIRT-3 to prevent cardiac oxidative stress and mitochondrial dysfunction in diabetes.

Background: Cardiac complications are major contributor in the mortality of diabetic people. Mitochondrial dysfunctioning is a crucial contributor for the cardiac complications in diabetes, and SIRT-3 remains the major mitochondrial deacetylase. We hypothesized whether garlic has any role on SIRT-3 to prevent mitochondrial dysfunction in diabetic heart.

Sirtuin 1 and 7 mediate resveratrol-induced recovery from hyper-anxiety in high-fructose-fed prediabetic rats.

Hyperglycaemia in diabetes is either caused by reduced availability of insulin (type 1 diabetes, T1D) or insulin resistance to the cells (type 2 diabetes, T2D). In recent years, the prevalence of T2D has increased to an alarming proportion, encompassing 95 percent of the total diabetic burden, probably due to economy-driven changes in lifestyle. Recent epidemiological studies show comorbid depression, anxiety and related mental illness.

Effect of resveratrol on sirtuins expression and cardiac complications in diabetes.

Sirtuins are the protein deacetylases, which are linked to metabolic diseases and aging. There are seven sirtuins present in cell, whose regulation in diabetic heart is yet to be explored. Resveratrol is a well-known activator of SIRT-1, but its effect on other sirtuins is not yet clear.

Resveratrol ameliorates cardiac oxidative stress in diabetes through deacetylation of NFkB-p65 and histone 3.

Resveratrol, a phytoalexin, has recently gained attention for protective effects against metabolic and cardiac diseases. The beneficial effects of resveratrol have been linked to sirtuin-1 (SIRT-1) activation. However, little is known about the effect of resveratrol in cardiac complications associated with diabetes.

Design, synthesis and evaluation of novel 2-butyl-4-chloroimidazole derived peptidomimetics as Angiotensin Converting Enzyme (ACE) inhibitors.

A series of novel 2-butyl-4-chloro-1-methylimidazole derived peptidomimetics were designed, synthesized and evaluated for their Angiotensin Converting Enzyme (ACE) inhibitor activity. 2-Butyl-4-chloro-1-methylimidazole-5-carboxylic acid 2 obtained after oxidation of respective carboxaldehyde 1, was condensed with various amino acid methyl esters 3a-k to give imidazole-amino acid conjugates 4a-k in very good yields. Ester hydrolysis of 4a-k with aqueous LiOH gave the desired peptidomimetics 5a-k.

Hyperglycaemia enhances nitric oxide production in diabetes: a study from South Indian patients.

Background: We have previously reported that increased glucose levels were associated with higher serum nitric oxide (NO) levels in fructose-fed insulin resistant rats. However, the relationship between hyperglycemia and serum NO level was not clear. Therefore, the present study was designed to find the association between hyperglycemia and serum NO levels in Type 2 diabetic (T2DM) patients and T2DM with cardiovascular complication.

Synthesis and evaluation of novel triazoles and mannich bases functionalized 1,4-dihydropyridine as angiotensin converting enzyme (ACE) inhibitors.

A series of novel diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate embedded triazole and mannich bases were synthesized, and evaluated for their angiotensin converting enzyme (ACE) inhibitory activity. Screening of above synthesized compounds for ACE inhibition showed that triazoles functionalized compounds have better ACE inhibitory activity compared to that of mannich bases analogues. Among all triazoles we found 6 h, 6 i and 6 j to have good ACE inhibition activity with IC50 values 0.

Design and green synthesis of 2-(diarylalkyl)aminobenzothiazole derivatives and their dual activities as angiotensin converting enzyme inhibitors and calcium channel blockers.

A series of novel 2-(diarylalkyl)aminobenzothiazoles were designed based on commercial synthetic calcium channel blockers (CCBs) and angiotensin converting enzyme (ACE) inhibitors. Which are further modified based on the natural products which are angiotensin converting enzyme (ACE) inhibitors. Completely green protocol was developed for their synthesis.

Synthesis and biological evaluation of new epalrestat analogues as aldose reductase inhibitors (ARIs).

Baylis-Hillman chemistry derived four series of new epalrestat analogues were synthesized. Three structural changes are introduced in these 39 new epalrestat analogues synthesized. All compounds were evaluated for their in vitro aldose reductase inhibitory (ALR) activity.

Insulin resistance, oxidative stress and cardiovascular complications: role of sirtuins.

Cardiovascular disease (CVD) is one of the major lifestyle associated disorders and leading causes of death worldwide. The incidence of CVD in diabetic patients has increased up to 3 folds and it became the major risk for diabetes associated morbidity and mortality. Insulin resistance and oxidative stress both play a central role in the pathogenesis and progression of diabetes.

Attenuation of insulin resistance, metabolic syndrome and hepatic oxidative stress by resveratrol in fructose-fed rats.

Metabolic syndrome and oxidative stress are common complications of type 2 diabetes mellitus. The present study was designed to determine whether resveratrol, a widely used nutritional supplement, can improve insulin sensitivity, metabolic complication as well as hepatic oxidative stress in fructose-fed rats. Male Sprague Dawley rats (180-200 g) were divided into four groups with 8 animals each.

Garlic improves insulin sensitivity and associated metabolic syndromes in fructose fed rats.

Background: Type 2 diabetes mellitus, characterized by peripheral insulin resistance, is a major lifestyle disorder of the 21st Century. Raw garlic homogenate has been reported to reduce plasma glucose levels in animal models of type 1 diabetes mellitus. However, no specific studies have been conducted to evaluate the effect of raw garlic on insulin resistance or type 2 diabetes mellitus.

Synthesis and evaluation of novel 2-butyl-4-chloro-1-methylimidazole embedded chalcones and pyrazoles as angiotensin converting enzyme (ACE) inhibitors.

A series of novel 2-butyl-4-chloro-1-methylimidazole embedded aryl and heteroaryl derived chalcones and pyrazoles were synthesized and evaluated for their angiotensin converting enzyme (ACE) inhibitory activity. The condensation of 2-butyl-4-chloro-1-methylimidazole-5-carboxaldehyde with various aryl and heteroaryl methyl ketones in the presence of 10% aqueous NaOH in methanol proceeded efficiently to give the respective chalcones in very good yields. Further, the reaction of chalcones with hydrazine hydrate in acetic acid gave substituted pyrazole analogues.