scholarly journals Anti-Inflammatory, Antidiabetic Properties and In Silico Modeling of Cucurbitane-Type Triterpene Glycosides from Fruits of an Indian Cultivar of Momordica charantia L.

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 1038 ◽  
Author(s):  
Wilmer H. Perera ◽  
Siddanagouda R. Shivanagoudra ◽  
Jose L. Pérez ◽  
Da Mi Kim ◽  
Yuxiang Sun ◽  
...  
Keyword(s):  
In Silico ◽  
Momordica Charantia ◽  
Innate Immune ◽  
Low Grade ◽  
Mitochondrial Marker ◽  
In Silico Docking ◽  
Tnf Α ◽  
In Silico Modeling ◽  
Low Grade Inflammation

Diabetes mellitus is a chronic disease and one of the fastest-growing health challenges of the last decades. Studies have shown that chronic low-grade inflammation and activation of the innate immune system are intimately involved in type 2 diabetes pathogenesis. Momordica charantia L. fruits are used in traditional medicine to manage diabetes. Herein, we report the purification of a new 23-O-β-d-allopyranosyl-5β,19-epoxycucurbitane-6,24-diene triterpene (charantoside XV, 6) along with 25ξ-isopropenylchole-5(6)-ene-3-O-β-d-glucopyranoside (1), karaviloside VI (2), karaviloside VIII (3), momordicoside L (4), momordicoside A (5) and kuguaglycoside C (7) from an Indian cultivar of Momordica charantia. At 50 µM compounds, 2–6 differentially affected the expression of pro-inflammatory markers IL-6, TNF-α, and iNOS, and mitochondrial marker COX-2. Compounds tested for the inhibition of α-amylase and α-glucosidase enzymes at 0.87 mM and 1.33 mM, respectively. Compounds showed similar α-amylase inhibitory activity than acarbose (0.13 mM) of control (68.0–76.6%). Karaviloside VIII (56.5%) was the most active compound in the α-glucosidase assay, followed by karaviloside VI (40.3%), while momordicoside L (23.7%), A (33.5%), and charantoside XV (23.9%) were the least active compounds. To better understand the mode of binding of cucurbitane-triterpenes to these enzymes, in silico docking of the isolated compounds was evaluated with α-amylase and α-glucosidase.

IL-6 as a Surrogate Biomarker: The IL-6 Clinical Value for the Diagnosis of Insulin Resistance and Type 2 Diabetes.

2021 ◽  
pp. 1-13
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Molecular Mechanisms ◽  
Diagnostic Value ◽  
Low Grade ◽  
Clinical Value ◽  
Insulin Resistant ◽  
Tnf Α ◽  
Low Grade Inflammation

1. Abstract Insulin Resistance is the leading cause of Type 2 diabetes mellitus (T2D). It occurs as a result of lipid disorders and increased levels of circulating free fatty acids (FFAs). FFAs accumulate within the insulin sensitive tissues such as muscle, liver and adipose tissues exacerbating different molecular mechanisms. Increased levels fatty acid has been documented to be strongly associated with insulin resistant states and obesity causing inflammation that eventually causes type 2-diabetes. Among the biomarkers that are accompanying low grade inflammation include IL-1β, IL-6 and TNF-α. The current review point out the importance of measuring the inflammatory biomarkers especially focusing on the conductance and measurement for IL-6 as a screening laboratory test and its diagnostic value in clinical practice.

Lipopolysaccharide activates an innate immune system response in human adipose tissue in obesity and type 2 diabetes

2007 ◽  
Vol 292 (3) ◽  
pp. E740-E747 ◽  
Author(s):  
S. J. Creely ◽  
P. G. McTernan ◽  
C. M. Kusminski ◽  
ff. M. Fisher ◽  
N. F. Da Silva ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Protein Expression ◽  
Serum Insulin ◽  
Human Adipose Tissue ◽  
Innate Immune ◽  
System Response ◽  
Low Grade ◽  
Tnf Α

Type 2 diabetes (T2DM) is associated with chronic low-grade inflammation. Adipose tissue (AT) may represent an important site of inflammation. 3T3-L1 studies have demonstrated that lipopolysaccharide (LPS) activates toll-like receptors (TLRs) to cause inflammation. For this study, we 1) examined activation of TLRs and adipocytokines by LPS in human abdominal subcutaneous (AbdSc) adipocytes, 2) examined blockade of NF-κB in human AbdSc adipocytes, 3) examined the innate immune pathway in AbdSc AT from lean, obese, and T2DM subjects, and 4) examined the association of circulating LPS in T2DM subjects. The findings showed that LPS increased TLR-2 protein expression twofold ( P < 0.05). Treatment of AbdSc adipocytes with LPS caused a significant increase in TNF-α and IL-6 secretion (IL-6, Control: 2.7 ± 0.5 vs. LPS: 4.8 ± 0.3 ng/ml; P < 0.001; TNF-α, Control: 1.0 ± 0.83 vs. LPS: 32.8 ± 6.23 pg/ml; P < 0.001). NF-κB inhibitor reduced IL-6 in AbdSc adipocytes (Control: 2.7 ± 0.5 vs. NF-κB inhibitor: 2.1 ± 0.4 ng/ml; P < 0.001). AbdSc AT protein expression for TLR-2, MyD88, TRAF6, and NF-κB was increased in T2DM patients ( P < 0.05), and TLR-2, TRAF-6, and NF-κB were increased in LPS-treated adipocytes ( P < 0.05). Circulating LPS was 76% higher in T2DM subjects compared with matched controls. LPS correlated with insulin in controls ( r = 0.678, P < 0.0001). Rosiglitazone (RSG) significantly reduced both fasting serum insulin levels (reduced by 51%, P = 0.0395) and serum LPS (reduced by 35%, P = 0.0139) in a subgroup of previously untreated T2DM patients. In summary, our results suggest that T2DM is associated with increased endotoxemia, with AT able to initiate an innate immune response. Thus, increased adiposity may increase proinflammatory cytokines and therefore contribute to the pathogenic risk of T2DM.

scholarly journals Vitamin D and inflammation in the prevention of type 2 diabetes: public health relevance

2012 ◽  
Vol 3 (4) ◽  
pp. 243
Author(s):  
Alaa Badawi ◽  
Eman Sadoun ◽  
Mohamed H. Al Thani
Keyword(s):  
Public Health ◽  
Type 2 Diabetes ◽  
Vitamin D ◽  
Immune System ◽  
Innate Immune System ◽  
Population Level ◽  
Innate Immune ◽  
Low Grade ◽  
Low Grade Inflammation

The incidence of type 2 diabetes mellitus (T2DM) is increasing worldwide. To reduce the disease risk and burden at the population level, preventative strategies should be developed with minimal cost and effort and with no side-effects. Low-grade inflammation resulting from imbalances in the innate immune system has been associated with an array of chronic disorders that predispose to the later development of T2DM (e.g., obesity, metabolic syndrome, and insulin resistance). As a result, inflammation may contribute to the pathogenesis of T2DM. Therefore, attenuation of this inflammatory response via modulating the innate immune system could lead to improved insulin sensitivity and delayed disease onset. Dietary supplementation with vitamin D may represent a novel strategy toward the prevention and control of T2DM at the population level due to its anti-inflammatory and antioxidant properties. This review examines current knowledge linking T2DM to chronic low-grade inflammation and the role of vitamin D in modulating this relationship. The concept that vitamin D, via attenuating inflammation, could be employed as a novel preventive measure for T2DM is evaluated in the context of its relevance to health care and public health practices.

scholarly journals Vitamin D and inflammation in the prevention of type 2 diabetes: public health relevance

2012 ◽  
Vol 3 (4) ◽  
pp. 243-255 ◽  
Author(s):  
Alaa Badawi ◽  
Eman Sadoun ◽  
Mohamed H. Al Thani
Keyword(s):  
Public Health ◽  
Type 2 Diabetes ◽  
Vitamin D ◽  
Immune System ◽  
Innate Immune System ◽  
Population Level ◽  
Innate Immune ◽  
Low Grade ◽  
Low Grade Inflammation

The incidence of type 2 diabetes mellitus (T2DM) is increasing worldwide. To reduce the disease risk and burden at the population level, preventative strategies should be developed with minimal cost and effort and with no side-effects. Low-grade inflammation resulting from imbalances in the innate immune system has been associated with an array of chronic disorders that predispose to the later development of T2DM (e.g., obesity, metabolic syndrome, and insulin resistance). As a result, inflammation may contribute to the pathogenesis of T2DM. Therefore, attenuation of this inflammatory response via modulating the innate immune system could lead to improved insulin sensitivity and delayed disease onset. Dietary supplementation with vitamin D may represent a novel strategy toward the prevention and control of T2DM at the population level due to its anti-inflammatory and antioxidant properties. This review examines current knowledge linking T2DM to chronic low-grade inflammation and the role of vitamin D in modulating this relationship. The concept that vitamin D, via attenuating inflammation, could be employed as a novel preventive measure for T2DM is evaluated in the context of its relevance to health care and public health practices.

Chronic Low Grade Inflammation in Type 2 Diabetes—Activation of the Inflammasomes by Circulating Metabolites

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1726-P
Author(s):  
MARIE MONLUN ◽  
VINCENT RIGALLEAU ◽  
LAURENCE BLANCO ◽  
KAMEL MOHAMMEDI ◽  
PATRICK BLANCO
Keyword(s):  
Type 2 Diabetes ◽  
Low Grade ◽  
Low Grade Inflammation

scholarly journals Adipose tissue inflammation and metabolic dysfunction: a clinical perspective

2013 ◽  
Vol 15 (1) ◽  
Author(s):  
Charmaine S. Tam ◽  
Leanne M. Redman
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Low Grade ◽  
Metabolic Dysfunction ◽  
Adipose Tissue Inflammation ◽  
Tissue Inflammation ◽  
Proinflammatory Mediators ◽  
Low Grade Inflammation

AbstractObesity is characterized by a state of chronic low-grade inflammation due to increased immune cells, specifically infiltrated macrophages into adipose tissue, which in turn secrete a range of proinflammatory mediators. This nonselective low-grade inflammation of adipose tissue is systemic in nature and can impair insulin signaling pathways, thus, increasing the risk of developing insulin resistance and type 2 diabetes. The aim of this review is to provide an update on clinical studies examining the role of adipose tissue in the development of obesity-associated complications in humans. We will discuss adipose tissue inflammation during different scenarios of energy imbalance and metabolic dysfunction including obesity and overfeeding, weight loss by calorie restriction or bariatric surgery, and conditions of insulin resistance (diabetes, polycystic ovarian syndrome).

Endothelial dysfunction and low-grade inflammation and the progression of retinopathy in Type 2 diabetes

2007 ◽  
Vol 24 (9) ◽  
pp. 969-976 ◽  
Author(s):  
A. M. W. Spijkerman ◽  
M.-A. Gall ◽  
L. Tarnow ◽  
J. W. R. Twisk ◽  
E. Lauritzen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Endothelial Dysfunction ◽  
Low Grade ◽  
Low Grade Inflammation

Activated Mast Cells Mediate Low-Grade Inflammation in Type 2 Diabetes: Interleukin-37 Could Be Beneficial

2018 ◽  
Vol 42 (5) ◽  
pp. 568-573 ◽  
Author(s):  
Pio Conti ◽  
Gianpaolo Ronconi ◽  
Spyridon K. Kritas ◽  
Alessandro Caraffa ◽  
Theoharis C. Theoharides
Keyword(s):  
Type 2 Diabetes ◽  
Mast Cells ◽  
Low Grade ◽  
Low Grade Inflammation

scholarly journals Puerarin Attenuates Obesity-Induced Inflammation and Dyslipidemia by Regulating Macrophages and TNF-Alpha in Obese Mice

Biomedicines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 175
Author(s):  
Ji-Won Noh ◽  
Hee-Kwon Yang ◽  
Min-Soo Jun ◽  
Byung-Cheol Lee
Keyword(s):  
Adipose Tissue ◽  
In Silico ◽  
Tolerance Test ◽  
Low Grade ◽  
Adipocyte Size ◽  
Metabolic Complications ◽  
Immunological Mechanisms ◽  
Tnf Α ◽  
Test Serum

Obesity causes low-grade inflammation that results in dyslipidemia and insulin resistance. We evaluated the effect of puerarin on obesity and metabolic complications both in silico and in vivo and investigated the underlying immunological mechanisms. Twenty C57BL/6 mice were divided into four groups: normal chow, control (HFD), HFD + puerarin (PUE) 200 mg/kg, and HFD + atorvastatin (ATO) 10 mg/kg groups. We examined bodyweight, oral glucose tolerance test, serum insulin, oral fat tolerance test, serum lipids, and adipocyte size. We also analyzed the percentage of total, M1, and M2 adipose tissue macrophages (ATMs) and the expression of F4/80, tumor necrosis factor-α (TNF-α), C-C motif chemokine ligand 2 (CCL2), CCL4, CCL5, and C-X-C motif chemokine receptor 4. In silico, we identified the treatment-targeted genes of puerarin and simulated molecular docking with puerarin and TNF, M1, and M2 macrophages based on functionally enriched pathways. Puerarin did not significantly change bodyweight but significantly improved fat pad weight, adipocyte size, fat area in the liver, free fatty acids, triglycerides, total cholesterol, and HDL-cholesterol in vivo. In addition, puerarin significantly decreased the ATM population and TNF-α expression. Therefore, puerarin is a potential anti-obesity treatment based on its anti-inflammatory effects in adipose tissue.

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