Antidiabetic Effect of Monolluma quadrangula Is Mediated via Modulation of Glucose Metabolizing Enzymes, Antioxidant Defenses, and Adiponectin in Type 2 Diabetic Rats

Monolluma quadrangula is a succulent bush traditionally used to treat diabetes and peptic ulcer. The present study aimed to investigate the effect of M. quadrangula hydroethanolic extract on glucose tolerance, insulin sensitivity, glucose metabolizing enzymes, lipid profile, and adiponectin expression in type 2 diabetic rats. In addition, the study evaluated the antioxidant and anti-inflammatory activities of the M. quadrangula extract. Type 2 diabetes was induced by feeding rats a high-fat diet (HFD) for 8 weeks followed by 30 mg/kg streptozotocin (STZ). Diabetic rats received 300 or 600 mg/kg M. quadrangula extract for 4 weeks. HFD/STZ diabetic rats showed impaired glucose tolerance, reduced insulin secretion, and insulin resistance. HFD and STZ induced a significant increase in serum cholesterol, triglycerides and proinflammatory cytokines, and liver lipid peroxidation. Treatment with M. quadrangula extract ameliorated these metabolic disturbances and increased liver glycogen, hexokinase activity, and antioxidants. M. quadrangula declined the activity of liver glucose-6-phosphatase and fructose-1,6-biphosphatase. In addition, M. quadrangula extract increased serum adiponectin levels and hepatic adiponectin expression in HFD/STZ diabetic rats. In conclusion, M. quadrangula exerts antidiabetic effect mediated via ameliorating glucose tolerance, insulin sensitivity, glucose metabolizing enzymes, and antioxidant defenses. Increased adiponectin levels and expression seems to mediate, at least in part, the antidiabetic effect of M. quadrangula

Monolluma quadrangula Protects against Oxidative Stress and Modulates LDL Receptor and Fatty Acid Synthase Gene Expression in Hypercholesterolemic Rats

Hypercholesterolemia is a metabolic disorder associated with oxidative stress. The present study investigated the protective effect of Monolluma quadrangula extract on hypercholesterolemia-induced oxidative stress in the liver and heart of high-cholesterol-diet- (HCD-) fed rats. The experimental animals received HCD for 10 weeks and were concurrently treated with 300 or 600 mg/kg M. quadrangula extract. HCD-fed rats showed a significant increase in serum triglycerides, total cholesterol, LDL-cholesterol, vLDL-cholesterol, and cardiovascular risk indices along with decreased HDL-cholesterol and antiatherogenic index. The M. quadrangula extract significantly improved dyslipidemia and atherogenesis in HCD-fed rats. HCD induced a significant increase in serum transaminases, creatine kinase-MB, and proinflammatory cytokines. In addition, HDC induced a significant increase in hepatic and cardiac lipid peroxidation and decreased antioxidant enzymes. Treatment with the M. quadrangula extract significantly alleviated liver and heart function markers, decreased proinflammatory cytokines and lipid peroxidation, and enhanced the antioxidant defenses. Also, the M. quadrangula extract significantly reduced the expression of fatty acid synthase (FAS) and increased the expression of LDL receptor in the liver of HCD-fed rats. In conclusion, the M. quadrangula extract has a potent antihyperlipidemic and cholesterol-lowering effect on HCD-fed rats. The beneficial effects of the M. quadrangula extract were mediated through the increased antioxidant defenses, decreased inflammation and lipid peroxidation, and modulated hepatic FAS and LDL receptor gene expression

Exploration of Cadmium Dioxide Nanoparticles on Bioaccumulation, Oxidative Stress, and Carcinogenic Potential in Oreochromis mossambicus L.

The field of nanotechnology is rapidly expanding with the advancement of novel nanopesticide and nanofertilizers that have the potential for revolutionizing applications in the agricultural industry. Here, we have done chronic toxicity of cadmium dioxide nanoparticles (CdONPs) on fish Oreochromis mossambicus (O. mossambicus) using oxidative stress and genotoxic biomarkers. In this current study, the value of LC50-96 hr of CdONPs has observed 40 μg/ml for O. mossambicus. The three sublethal concentrations, e.g., 4, 10, and 20 μg/ml were selected based on the LC50 value. The fishes were treated to the above concentration of CdONPs for 21 days and were harvested at 1, 7, 14, and 21 days for evaluation of clastogenicity, mutagenicity, and genotoxicity of NPs. Generally, significant effects (p<0.01) were observed as a dose and duration of exposure. It was observed that lipid peroxidation (LPO) was increased and glutathione was decreased in both tissues. Micronuclei (MNi) were produced significantly in peripheral blood on 21 days at maximum concentration. A similar trend was seen in the damage of DNA with the same manner in terms of the percentage of tail DNA in the lymphocyte, gills, and kidney cells. This study explored the application oxidative stress, comet assay, and micronucleus assay for in situ aquatic laboratory studies using fish O. mossambicus for screening the ecomutagenic and genotoxic potential of environmental pollutants

Cadmium cardiotoxicity is associated with oxidative stress and upregulated TLR-4/NF-kB pathway in rats; protective role of agomelatine

Cardiotoxicity is one of the hazardous effects of the exposure to the heavy metal cadmium (Cd). Inflammation and oxidative injury are implicated in the cardiotoxic mechanism of Cd. The melatonin receptor agonist agomelatine (AGM) showed promising effects against oxidative and inflammatory responses. This study evaluated the effect of AGM on Cd-induced cardiotoxicity in rats, pointing to its modulatory effect on TLR-4/NF-kB pathway and HSP70. Rats received AGM for 14 days and a single dose of Cd on day 7 and blood and heart samples were collected for analyses. Cd increased serum CK-MB, AST and LDH and caused cardiac tissue injury. Cardiac malondialdehyde (MDA), nitric oxide (NO) and MPO were elevated and GSH, SOD and GST decreased in Cd-administered rats. AGM ameliorated serum CK-MB, AST and LDH and cardiac MDA, NO and MPO, prevented tissue injury and enhanced antioxidants. AGM downregulated serum CRP and cardiac TLR-4, NF-kB, iNOS, IL-6, TNF-α and COX-2 in Cd-administered rats. HSP70 was upregulated in the heart of Cd-challenged rats treated with AGM. In silico findings revealed the binding affinity of AGM with TLR-4 and NF-kB. In conclusion, AGM protected against Cd cardiotoxicity by preventing myocardial injury and oxidative stress and modulating HSP70 and TLR-4/NF-kB pathway

Cadmium-induced lung injury is associated with oxidative stress, apoptosis, and altered SIRT1 and Nrf2/HO-1 signaling; protective role of the melatonin agonist agomelatine

Cadmium (Cd) is a hazardous heavy metal extensively employed in manufacturing polyvinyl chloride, batteries, and other industries. Acute lung injury has been directly connected to Cd exposure. Agomelatine (AGM), a melatonin analog, is a drug licensed for treating severe depression. This study evaluated the effect of AGM against Cd-induced lung injury in rats. AGM was administered in a dose of 25 mg/kg/day orally, while cadmium chloride (CdCl2) was injected intraperitoneally in a dose of 1.2 mg/kg to induce lung injury. Pre-treatment with AGM remarkably ameliorated Cd-induced lung histopathological abrasions. AGM decreased reactive oxygen species (ROS) production, lipid peroxidation, suppressed NDAPH oxidase, and boosted the antioxidants. AGM increased Nrf2, GCLC, HO-1, and TNXRD1 mRNA, as well as HO-1 activity and downregulated Keap1. AGM downregulated Bax and caspase-3 and upregulated Bcl-2, SIRT1, and FOXO3 expression levels in the lung. In conclusion, AGM has a protective effect against Cd-induced lung injury via its antioxidant and anti-apoptotic effects mediated via regulating Nrf2/HO-1 and SIRT1/FOXO3 signaling

Recent Development of Catalytic Materials for Ethylbenzene Oxidation

Catalysts are well-known to convert alkylbenzenes at high thermal condition to a number of useful products. However, the current schemes of transformation are not suitable for the hazard-free industrial applications because their reactive intermediates are transformed to a variety of side products that often retard the optimum yield and cause environmental pollutions. It is also observed that the formation of products depends on a wide range of parameters which are extremely difficult to control and often incur extra cost. Recently, heterogeneous catalysts have received huge commercial interests for the oxidation of alkylbenzene into carbonyl compounds which are platform chemicals in various synthetics and fine chemicals. This review is an up-to-date documentary on various catalysts used for the oxidation of alkyl-substituted benzenes along with their reaction condition and selectivity profiles. This work updates our knowledge for the selection and/or design of novel catalysts for the chemists and engineers in the industrial and academic settings

The impact of proteostasis dysfunction secondary to environmental and genetic causes on neurodegenerative diseases progression and potential therapeutic intervention

International audienceAggregation of particular proteins in the form of inclusion bodies or plaques followed by neuronal death is a hallmark of neurodegenerative proteopathies such as primary Parkinsonism, Alzheimer’s disease, Lou Gehrig’s disease, and Huntington’s chorea. Complex polygenic and environmental factors implicated in these proteopathies. Accumulation of proteins in these disorders indicates a substantial disruption in protein homeostasis (proteostasis). Proteostasis or cellular proteome homeostasis is attained by the synchronization of a group of cellular mechanisms called the proteostasis network (PN), which is responsible for the stability of the proteome and achieves the equilibrium between synthesis, folding, and degradation of proteins. In this review, we will discuss the different types of PN and the impact of PN component dysfunction on the four major neurodegenerative diseases mentioned earlier

Novel Anti-Alzheimer’s Therapeutic Molecules Targeting Amyloid Precursor Protein Processing

Alzheimer’s disease (AD) is the most common cause of dementia among older people, and the prevalence of this disease is estimated to rise quickly in the upcoming years. Unfortunately, almost all of the drug candidates tested for AD until now have failed to exhibit any efficacy. Henceforth, there is an increased necessity to avert and/or slow down the advancement of AD. It is known that one of the major pathological characteristics of AD is the presence of senile plaques (SPs) in the brain. These SPs are composed of aggregated amyloid beta (Aβ), derived from the amyloid precursor protein (APP). Pharmaceutical companies have conducted a number of studies in order to identify safe and effective anti-Aβ drugs to combat AD. It is known that α-, β-, and γ-secretases are the three proteases that are involved in APP processing. Furthermore, there is a growing interest in these proteases, as they have a contribution to the modulation and production of Aβ. It has been observed that small compounds can be used to target these important proteases. Indeed, these compounds must satisfy the common strict requirements of a drug candidate targeted for brain penetration and selectivity toward different proteases. In this article, we have focused on the auspicious molecules which are under development for targeting APP-processing enzymes. We have also presented several anti-AD molecules targeting Aβ accumulation and phosphorylation signaling in APP processing. This review highlights the structure-activity relationship and other physicochemical features of several pharmacological candidates in order to successfully develop new anti-AD drugs