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Type two Diabetes Mellitus (T2DM) is a rising epidemic. Available therapeutic strategies have provided glycaemic control via HbA1c reduction but fail to provide clinically meaningful reduction in microvascular and macrovascular (cardiac, renal, ophthalmological, and neurological) complications. Inflammation is strongly linked to the pathogenesis of T2DM. Underlying inflammatory mechanisms include oxidative stress, endoplasmic reticulum stress amyloid deposition in the pancreas, lipotoxicity, and glucotoxicity. Molecular signalling mechanisms in chronic inflammation linked to obesity and diabetes include JANK, NF-kB, and AMPK pathways. These activated pathways lead to a production of various inflammatory cytokines, such as Interleukin (IL-6), tumor necrosis factor (TNF)-alpha, and C-reactive protein (CRP), which create a chronic low-grade inflammation and ultimately dysregulation of glucose homeostasis in the liver, skeletal muscle, and smooth muscle. Anti-inflammatory agents are being tested as anti-diabetic agents such as the IL-1b antagonist, Anakinra, the IL-1b inhibitor, Canakinuma, the IL-6 antagonists such as Tocilizumab, Rapamycin (Everolimus), and the IKK-beta kinase inhibitor, Salsalate. Salsalate is a century old safe anti-inflammatory drug used in the treatment of arthritis. Long-term safety and efficacy of Salsalate in the treatment of T2DM have been evaluated, which showed improved fasting plasma glucose and reduced HbA1C levels as well as reduced pro-inflammatory markers in T2DM patients. Current publication summarizes the literature review of pathophysiology of role of inflammation in T2DM and clinical efficacy and safety of Salsalate in the treatment of T2DM. [ABSTRACT FROM AUTHOR]

Introduction: Pain is a serious adverse event which frequently accompanies hematopoietic stem cell transplantation (HSCT). The safety and efficacy of NSAIDS during HSCT is currently unknown. Salsalate is a platelet-sparing NSAID with a favorable toxicity profile compared with other NSAIDS. We report the safety and efficacy of salsalate for different types of pain during SCT.Methods: We conducted a retrospective study of SCT recipients empirically treated with salsalate for > 48 h. Pain scores were assessed using the verbal rating scale for pain. A subset analysis of patients who received > 7 days of salsalate during periods of pancytopenia, mucositis, and other end-organ toxicities is included.Results: Sixty-four patients, 42 auto- and 22 allografts, were identified. Reason for use: vertebral-related pain (30%), musculoskeletal (30%), and cytokine inflammatory pain syndromes (24%). Median dose 1500 mg/day, number of treatment days = 5, started on day+5 post-HSCT. Pain resolved/improved to pain score < 4 in 76% and stable in 15%. Forty-four patients (28-auto and 16 allografts) received > 7-day salsalate. Median WBC and platelet nadir were < 0.1 and 10,000 cells/ml respectively.Efficacy: pain was improved or eradicated in 64% and stable in 32%.Toxicity: LFT elevation (n = 2), elevated serum creatinine (n = 2), and minor bleed (n = 5-nose, gums, and urine). Salsalate discontinuation (n = 6): ineffective (n = 1), the liver (n = 1), the kidney (n = 1), > 5 platelet transfusions (n = 1), and vomiting (n = 2). There was no treatment related mortality. Salsalate was well tolerated, safe, and beneficial for several different types of pain during HSCT. [ABSTRACT FROM AUTHOR]

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Objective and design: Inflammation plays a causative role in atherosclerosis development. Salsalate is an anti-inflammatory drug used to treat atherosclerosis, but the mechanisms by which it affects atherosclerotic progression remain unclear. Methods: Human umbilical vascular endothelial cells (HUVECs) and THP-1 human monocytes were treated with salsalate. Heme oxygenase 1 (HO-1) and sirtuin 1 (SIRT1) small interfering RNAs (siRNAs) were used to suppress each gene expression. Protein analyses were performed for measuring the expression of HO-1, SIRT1, nuclear factor kappa B (NFκB), cell adhesion molecules, and endoplasmic reticulum (ER) stress markers. Furthermore, cell adhesion assay, caspase 3 activity assay, and ELISA were also performed. Results: In this study, we show that salsalate increases the expression of HO-1 and SIRT1 in HUVEC and suppresses lipopolysaccharide (LPS)-induced atherosclerotic responses via HO-1- and SIRT1-mediated pathways. Salsalate treatment of HUVEC and THP-1 cells reduced LPS-induced phosphorylation of NFκB and secretion of the proinflammatory cytokines TNFα and MCP-1. Salsalate treatment of HUVEC reduced the expression of the adhesion molecules ICAM, VCAM, and E-selectin and the LPS-induced adhesion of THP-1 cells to HUVEC. Salsalate treatment also attenuated LPS-induced ER stress and cell apoptosis. These anti-atherosclerotic effects were reversed by treating cells with siRNA for HO-1 and SIRT1. Conclusions: Salsalate ameliorates LPS-induced atherosclerotic reactions via HO-1 and SIRT1-dependent reduction of inflammation and ER stress. Activation of these pathways by salsalate may provide therapeutic strategies for treating atherosclerosis. [ABSTRACT FROM AUTHOR]

Efficacy of salicylic acid as a treatment for diabetes was first established well over a century ago. Antihyperglycaemic effects are thought to include improved peripheral insulin sensitivity and suppression of hepatic glucose production. For most of this period, the molecular mechanisms underlying these effects have been poorly understood and these are still a focus of considerable research, which is reviewed here. Antihyperglycaemic effects are observed only at much higher concentrations than analgesic, antipyretic and antithrombotic properties, suggesting that different targets underlie the antidiabetic aspects of salicylate pharmacology. In the 1950s, antihyperglycaemic responses were linked to mitochondrial uncoupling effects of the drug. Then at the beginning of this century, antihyperglycaemic effects were linked to anti-inflammatory effects of the drug on NF-κB signalling. More recently, new work suggests that direct activation of AMPK may contribute to antihyperglycaemic/antihyperlipidemic actions of salicylates. Better understanding of the mechanism of salicylate's anthyperglycaemic effects may ultimately accelerate the development of new drugs for human use. [ABSTRACT FROM AUTHOR]

Chronic inflammation contributes to insulin resistance and type 2 diabetes mellitus (T2DM). We investigated whether treatment with salsalate, an anti-inflammatory medication, improves glycemia in a group of newly diagnosed drug-naïve patients with T2DM. The study was a randomized, double-blind, placebo-controlled trial. Diagnosis of T2DM was made within 2 months of enrollment, and participants had not received any anti-glycemic agent. Sixty adults were randomized to receive salsalate (3 g/day) or placebo for 12 weeks. Fasting plasma glucose and insulin, glucose 2 h after 75 g oral glucose, HbA1C, lipid profile, HOMA-IR, and HOMA-B were determined before and after treatment. Salsalate reduced fasting glucose from 6.3 ± 0.2 mmol/l to 5.4 ± 0.2 mmol/l ( P < 0.01) and TG from 1.9 ± 0.2 mmol/l to 1.5 ± 0.2 mmol/l ( P < 0.03). Fasting insulin levels were increased in the salsalate group from 18.8 ± 1.6 to 21.6 ± 3.9, while they decreased in the placebo group. HbA1c rose in the placebo group from 6.2% ± 0.2 to 7.9% ± 1.1 mmol/mol, but decreased in the intervention group from 6.1% ± 0.5 to 5.6% ± 0.2 mmol/mol ( P < 0.04 for between-group comparison). HOMA-IR did not change but HOMA-B increased ~1.7-fold ( P = 0.06) in the salsalate group. The results show that salsalate is effective in improving glycemic control in newly diagnosed naïve patients with T2DM. The optimal duration of treatment with salsalate and sustainability of its effect requires further study (IRCT138709011465N1). [ABSTRACT FROM AUTHOR]

The thermal behaviour of salicylsalicylic acid (CAS number 552-94-3) was studied by differential scanning calorimetry (DSC). The endothermic melting peak and the fingerprint of the glass transition were characterised at a heating rate of 10°C min-1. The melting peak showed an onset at Ton = 144°C (417 K) and a maximum intensity at Tmax = 152°C (425 K), while the onset of the glass transition signal was at Ton = 6°C. The melting enthalpy was found to be ΔmH = 28.9±0.3 kJ mol-1, and the heat capacity jump at the glass transition was ΔCP = 108.1±0.1 J K-1 mol-1. The study of the influence of the heating rate on the temperature location of the glass transition signal by DSC, allowed the determination of the activation energy at the glass transition temperature (245 kJ mol-1), and the calculation of the fragility index of salicyl salicylate (m = 45). Finally, the standard molar enthalpy of formation of crystalline monoclinic salicylsalicylic acid at T = 298.15 K, was determined as ΔfHmo(C14H10O5, cr) = - (837.6±3.3) kJ mol-1, by combustion calorimetry. [ABSTRACT FROM AUTHOR]