Evaluation of the Influence of thiosemicarbazone–triazole hybrids on genes implicated in lipid oxidation and accumulation as potential anti-obesity agents

Kinfe, Henok H.; Belay, Yonas H.; Joseph, Jitcy S.; Mukwevho, Emmanuel

doi:10.1016/j.bmcl.2013.08.028

Cited by 19 publications

(6 citation statements)

References 31 publications

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“…High fructose diet induced elevation in cytokine levels and was attenuated when these rats were treated with oleanolic acid, indicating the potential of OA in ameliorating symptoms of T2D and obesity. High fructose effects are consistent with the notion that diet and in particular high carbohydrate levels, have deleterious effects on normal functioning of metabolic processes of the cell and are a major contributor to health problems such as T2D and obesity [38,39,40,41,42,43,44,45,46].…”

Section: Discussionsupporting

confidence: 83%

Long-Term Impact of Neonatal Intake of Oleanolic Acid on the Expression of AMP-Activated Protein Kinase, Adiponectin and Inflammatory Cytokines in Rats Fed with a High Fructose Diet

et al. 2019

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AMP-activated protein kinase (AMPK) is known to regulate both glucose and lipid metabolism, which play vital roles in the development of metabolic syndrome. One way of regulating AMPK is through hormonal activation using adiponectin. Patients diagnosed with type-2 diabetes (T2D) and obesity exhibit low adiponectin concentration levels in their blood. Moreover, studies have also shown that inflammatory processes play a significant role in the etiology of these metabolic diseases. In this study, the long-term effects of neonatal intake of oleanolic acid (OA) on the AMPK gene, genes associated with glucose transport and lipid metabolism, adiponectin levels, and inflammatory biomarkers in rats fed with a high fructose diet were investigated. Seven day old pups were randomly divided into five groups and treated as follows; 0.5% dimethylsulphoxide v/v in distilled water vehicle control (CON), oleanolic acid (OA, 60 mg/kg), high fructose diet (HF, 20% w/v), high fructose diet combined with oleanolic acid (HF+OA), and high fructose diet combined with metformin (HF+MET, 500 mg/kg). The treatments were administered once daily until day 14. The rats were then weaned at day 21 and fed standard rat chow and had ad libitum access to plain drinking water until day 112. The quantitative polymerase chain reaction (qPCR) was used to analyze the gene expressions of AMPK, Glut-4, Cpt-1, AdipoR1, AdipoR2, TNF-α, and IL-6 in the skeletal muscles. Bio-Plex Pro magnetic bead-based assay was used to measure plasma levels of inflammatory markers (TNF-α, IL-6, VEGF, and MCP-1) while ELISA kits were used to measure adiponectin concentration in blood plasma. The results obtained in this study showed that neonatal supplementation with OA significantly increased AMPK gene expression approximately ~4-fold in OA fed rats compared to those that were fed with HF alone. In addition, glut-4 gene expression was also significantly higher in the OA treatment group compared to all the other experimental groups except the CON group whereas Cpt-1 gene was more expressed when OA was administered alone. Together, these results indicated that OA can play a role in glucose and lipid metabolism gene regulation. Furthermore, the results showed that the OA group had ~1.5-fold increase in adiponectin concentration when comparedto the HF group. Moreover, HF increased levels of inflammatory cytokines, which was attenuated by neonatal administration of OA. Plasma concentration and gene expression in the skeletal muscle for TNF-α and IL-6 were significantly increased in rats that were treated with HF alone when compared to all the other groups. On the contrary, the high levels of TNF-α and IL-6 were reduced when OA was administered. These findings suggest that intake of oleanolic acid during the neonatal stage of development could be a potential strategic intervention for the long-term prevention of metabolic diseases such as T2D and obesity.

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Section: Discussionsupporting

confidence: 83%

Long-Term Impact of Neonatal Intake of Oleanolic Acid on the Expression of AMP-Activated Protein Kinase, Adiponectin and Inflammatory Cytokines in Rats Fed with a High Fructose Diet

et al. 2019

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“…The synthesis of the hybrid compounds ( 2b-h) were synthesized in a similar fashion as published by [ 17 , 18 ] except for the addition of an electron donating group (methoxy substituent to C(4) position of the aromatic ring joining thiosemicarbazone and triazole..…”

Section: Methodsmentioning

confidence: 99%

Evaluation of free radical scavenging capacity of methoxy containing-hybrids of thiosemicarbazone-triazole and their influence on glucose transport

Ayeleso

Joseph

Oguntibeju

et al. 2018

BMC Pharmacol Toxicol

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BackgroundDiabetes mellitus is a metabolic disease in which the body is unable to produce insulin or respond to insulin production, consequently leading to abnormal metabolism of carbohydrates, lipids and proteins causing elevation of glucose in the blood. Oxidative stress, an imbalance between the production of free radicals and body antioxidant system has been implicated in the pathogenesis of diabetes. Free radicals attack important macromolecules leading to cell damage. Antioxidants are intimately involved in the prevention of damage caused by free radicals.MethodsThe anti-diabetic effects of hybrid compounds (2a-h) of thiosemicarbazone and triazole containing methoxy groups at C (4) positions were tested against genes involved in glucose metabolism (Glut-4, Mef2a and Nrf-1) using quantitative real time PCR (qPCR). Free radical scavenging capacity (FRAP, TEAC, DPPH and ORAC) of the hybrids was also carried out by using established antioxidant capacity assays.ResultsFrom the results, hybrid compounds 2b and 2h showed more pronounced effects in up-regulating diabetes associated genes which are important in the up-regulation of glucose uptake. All the hybrid compounds also showed free radical scavenging abilities.ConclusionIn conclusion, hybrid compounds (2b and 2h) can be useful as potential drugs for the management of diabetes mellitus.

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“…In our previous studies, we investigated the role of antioxidant-rich natural plant products and newly synthesized novel thiazolidinediones (TZDs) hybrid compounds in relation to diabetes mellitus and obesity [28,29]. From our results, an increased lipid peroxidation due to the production of ROS in diabetic conditions was shown [28].…”

Section: Oxidative Environment In a Biological Systemmentioning

confidence: 99%

“…The natural products (red palm oil and rooibos) used in the study showed protective effects against oxidative stress by improving the antioxidant status. Furthermore, the hybrid compounds improved the expression of genes that are associated with lipid metabolism [29]. In our recent studies, new synthesized TZDs hybrid compounds have also shown good antioxidant activities that could be helpful in combating the deleterious effects of ROS (unpublished data).…”

Section: Oxidative Environment In a Biological Systemmentioning

confidence: 99%

Potential Role of Sulfur-Containing Antioxidant Systems in Highly Oxidative Environments

2014

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All forms of life maintain a reducing environment (homeostasis) within their cells. Perturbations in the normal redox state can lead to an oxidative environment which has deleterious effects, especially in health. In biological systems, metabolic activities are dependent mainly on mitochondrial oxidative phosphorylation, a metabolic pathway that uses energy released by the oxidation of nutrients to produce ATP. In the process of oxidative phosphorylation, electrons are transferred from electron donors to electron acceptors such as oxygen in redox reactions and often results to the generation of reactive species. Reactive oxygen species consist of a class of radical and non-radical oxygen derivatives. The imbalance between the reactive oxygen species and antioxidant defence systems leads to oxidative burden and hence, damage biological molecules. Antioxidants help to prevent or fix the deleterious effects of reactive species. Sulfur is an important element in biological systems. This atom is usually integrated into proteins as the redox-active cysteine residue and in molecules such as glutathione, thioredoxin and glutaredoxin which are vital antioxidant molecules and are therefore essential for life. This review covers the role of sulfur containing antioxidant systems in oxidative environments.

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Evaluation of the Influence of thiosemicarbazone–triazole hybrids on genes implicated in lipid oxidation and accumulation as potential anti-obesity agents

Cited by 19 publications

References 31 publications

Long-Term Impact of Neonatal Intake of Oleanolic Acid on the Expression of AMP-Activated Protein Kinase, Adiponectin and Inflammatory Cytokines in Rats Fed with a High Fructose Diet

Long-Term Impact of Neonatal Intake of Oleanolic Acid on the Expression of AMP-Activated Protein Kinase, Adiponectin and Inflammatory Cytokines in Rats Fed with a High Fructose Diet

Evaluation of free radical scavenging capacity of methoxy containing-hybrids of thiosemicarbazone-triazole and their influence on glucose transport

Potential Role of Sulfur-Containing Antioxidant Systems in Highly Oxidative Environments

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