Anti-inflammatory Agents in the Treatment of Diabetes and Its Vascular Complications

Diabetes mellitus is a metabolic disorder characterized by the development of vascular complications associated with high morbidity and mortality and the consequent relevant costs for the public health systems. Diabetic kidney disease is one of these complications that represent the main cause of end-stage renal disease in Western countries. Hyperglycemia, inflammation, and oxidative stress contribute to its physiopathology, and several investigations have been performed to evaluate the role of antioxidant supplementation as a complementary approach for the prevention and control of diabetes and associated disturbances. Vitamin E compounds, including different types of tocopherols and tocotrienols, have been considered as a treatment to tackle major cardiovascular outcomes in diabetic subjects, but often with conflicting or even negative results. However, their effects on diabetic nephropathy are even less clear, despite several intervention studies that showed the improvement of renal parameters after supplementation in patients with diabetic kidney disease. Then we performed a review of the literature about the role of vitamin E supplementation on diabetic nephropathy, also describing the underlying antioxidant, anti-inflammatory, and metabolic mechanisms to evaluate the possible use of tocopherols and tocotrienols in clinical practice.

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Anti- inflammatory effect of Prunus tomentosa Thunb total flavones in LPS-induced RAW264.7 cells

Open Chemistry ◽

10.1515/chem-2019-0076 ◽

2019 ◽

Vol 17 (1) ◽

pp. 685-693

Author(s):

Chen Xi ◽

Liu Yuanyuan ◽

Zhao Dongshuang ◽

Fan Ziwei ◽

Cao Shuang ◽

...

Keyword(s):

Significant Inhibition ◽

Raw264.7 Cells ◽

Supernatant Fraction ◽

Treatment Of Diabetes ◽

Cox 2 ◽

Anti Inflammatory ◽

The Impact ◽

Cox 1 ◽

Inflammatory Effect

AbstractIn this research, we investigated possible anti-inflammatory roles of Prunus tomentosa Thunb Total Flavones (PTTTF) in LPS-induced RAW264.7 cells. PTTTF (4μg/ml and 40μg/ml) was applied to RAW264.7 cells induced with 1μg/ml LPS to test the impact of these flavones on neutrophil phagocytosis in vitro. Levels of prostaglandin E2 (PGE2) and two pro-inflammatory interleukin cytokines (i.e. IL-6 and IL-1β) in the supernatant fraction were tested via Enzyme-linked immunosorbent assays (ELISA). Expression of cyclooxygenases COX-1 and COX-2 was detected via RT-PCR. Superoxide dismutase (SOD) content was determined with a spectrophotometric assay (Micromethod). The results revealed that PTTTF at doses higher than 4μg/ml reduces the content of IL-6, IL-1β and PGE2 (P < 0.05), and elevates the activity of SOD in LPS-induced RAW264.7 cells significantly (P < 0.05). PTTTF at 40μg/ml showed no significant effect on the expression of COX-1(P>0.05) but resulted in a significant inhibition of COX-2 in LPS-induced RAW264.7 cells (P<0.05). In summary, PTTTF had a substantial potential anti-inflammatory effect through the alteration of the synthesis of some cytokines and other mediators of the process of inflammation. Novelty statement - Prunus tomentosa Thunb Total Flavones (PTTTF) have known roles in the treatment of diabetes, but here we show that they are also potential anti-inflammatory agents. Our results show that PTTTF exhibited anti-inflammatory effects through altering the synthesis of some cytokines and other mediators of the inflammatory process.

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The Role of Insulin Receptor Isoforms in Diabetes and Its Metabolic and Vascular Complications

Journal of Diabetes Research ◽

10.1155/2017/1403206 ◽

2017 ◽

Vol 2017 ◽

pp. 1-12 ◽

Cited By ~ 18

Author(s):

O. Escribano ◽

N. Beneit ◽

C. Rubio-Longás ◽

A. R. López-Pastor ◽

A. Gómez-Hernández

Keyword(s):

Insulin Receptor ◽

Vascular Complications ◽

Cell Types ◽

Metabolic Effects ◽

Future Research ◽

Receptor Isoforms ◽

Insulin Receptor Isoforms ◽

Treatment Of Diabetes ◽

Different Cell Types

The insulin receptor (IR) presents by alternative splicing two isoforms: IRA and IRB. The differential physiological and pathological role of both isoforms is not completely known, and it is determinant the different binding affinity for insulin-like growth factor. IRB is more abundant in adult tissues and it exerts mainly the metabolic actions of insulin, whereas IRA is mainly expressed in fetal and prenatal period and exerts mitogenic actions. However, the change in the expression profile of both IR isoforms and its dysregulation are associated with the development of different pathologies, such as cancer, insulin resistance, diabetes, obesity, and atherosclerosis. In some of them, there is a significant increase of IRA/IRB ratio conferring a proliferative and migratory advantage to different cell types and favouring IGF-II actions with a sustained detriment in the metabolic effects of insulin. This review discussed specifically the role of IR isoforms as well as IGF-IR in diabetes and its associated complications as obesity and atherosclerosis. Future research with new IR modulators might be considered as possible targets to improve the treatment of diabetes and its associated complications.

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Bitter Gourd Honey Ameliorates Hepatic and Renal Diabetic Complications on Type 2 Diabetes Rat Models by Antioxidant, Anti-Inflammatory, and Anti-Apoptotic Mechanisms

Foods ◽

10.3390/foods10112872 ◽

2021 ◽

Vol 10 (11) ◽

pp. 2872

Author(s):

Chandra Sekhar Arigela ◽

Giribabu Nelli ◽

Siew Hua Gan ◽

Kuttulebbai Nainamohamed Salam Sirajudeen ◽

Kumarathevan Krishnan ◽

...

Keyword(s):

Oxidative Stress ◽

Diabetic Complications ◽

Diabetic Rats ◽

Male Rats ◽

Bitter Gourd ◽

Liver And Kidney ◽

Streptozotocin Induced Diabetes ◽

Treatment Of Diabetes ◽

Anti Inflammatory ◽

Apoptotic Effects

Honey has several pharmacological effects, including anti-diabetic activity. However, the effectiveness of bitter gourd honey (BGH) in the treatment of diabetes mellitus (DM) is unknown. The aim of this study was to determine the antioxidant, anti-inflammatory, and anti-apoptotic properties of BGH on the kidney and liver of a streptozotocin-induced diabetes rat model. Methods: A single dose (nicotinamide 110 mg/kg, streptozotocin (STZ) 55 mg/kg, intraperitoneal (i.p.)) was used to induce DM in male rats. For 28 days, normal or diabetic rats were administered 1 g/kg/day and 2 g/kg/day of BGH orally. After the treatment, blood, liver, and kidney samples were collected and analysed for biochemical, histological, and molecular parameters. In addition, liquid chromatography–mass spectrometry (LC-MS) was used to identify the major bioactive components in BGH. Results: The administration of BGH to diabetic rats resulted in significant reductions in alanine transaminase (ALT),aspartate aminotransferase (AST), creatinine, and urea levels. Diabetic rats treated with BGH showed lesser pathophysiological alterations in the liver and kidney as compared to non-treated control rats. BGH-treated diabetic rats exhibited reduced levels of oxidative stress (MDA levels), inflammatory (MYD88, NFKB, p-NFKB, IKKβ), and apoptotic (caspase-3) markers, as well as higher levels of antioxidant enzymes (SOD, CAT, and GPx) in the liver and kidney. BGH contains many bioactive compounds that may have antioxidative stress, anti-inflammatory, and anti-apoptotic effects. Conclusion: BGH protected the liver and kidney in diabetic rats by reducing oxidative stress, inflammation, and apoptosis-induced damage. As a result, BGH can be used as a potential therapy to ameliorate diabetic complications.

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Sex Differences of the Diabetic Heart

Frontiers in Physiology ◽

10.3389/fphys.2021.661297 ◽

2021 ◽

Vol 12 ◽

Author(s):

Natacha Fourny ◽

Christophe Beauloye ◽

Monique Bernard ◽

Sandrine Horman ◽

Martine Desrois ◽

...

Keyword(s):

Sex Differences ◽

Animal Studies ◽

Molecular Mechanisms ◽

Vascular Complications ◽

Clinical Findings ◽

Personalized Care ◽

Increased Risk ◽

Treatment Of Diabetes ◽

The Impact

Type 2 diabetes is a chronic disease associated with micro- and macro-vascular complications, including myocardial ischemia, and also with a specific and intrinsic cardiac dysfunction called diabetic cardiomyopathy (DCM). Both clinical and animal studies demonstrate significant sex differences in prevalence, pathophysiology, and outcomes of cardiovascular diseases (CVDs), including those associated with diabetes. The increased risk of CVDs with diabetes is higher in women compared to men with 50% higher risk of coronary artery diseases and increased mortality when exposed to acute myocardial infarction. Clinical studies also reveal a sexual dimorphism in the incidence and outcomes of DCM. Based on these clinical findings, growing experimental research was initiated to understand the impact of sex on CVDs associated with diabetes and to identify the molecular mechanisms involved. Endothelial dysfunction, atherosclerosis, coagulation, and fibrosis are mechanisms found to be sex-differentially modulated in the diabetic cardiovascular system. Recently, impairment of energy metabolism also emerged as a determinant of multiple CVDs associated with diabetes. Therefore, future studies should thoroughly analyze the sex-specific metabolic determinants to propose new therapeutic targets. With current medicine tending toward more personalized care of patients, we finally propose to discuss the importance of sex as determinant in the treatment of diabetes-associated cardiac diseases to promote a more systemic inclusion of both males and females in clinical and preclinical studies.

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