New Glycotoxin Inhibitor from Sesuvium sesuvioides Mitigates Symptoms of Insulin Resistance and Diabetes by Suppressing AGE-RAGE Axis in Skeletal Muscle

被引：0

作者：

Ghaffar, Safina ^{[1
,2
]}

Waraich, Rizwana Sanaullah ^{[1
]}

Orfali, Raha ^{[2
]}

Al-Taweel, Areej ^{[2
]}

Aati, Hanan Y. ^{[2
]}

Kamran, Sonia ^{[3
]}

Perveen, Shagufta ^{[4
]}

机构：

[1] Sohail Univ, Biomed Res Ctr, Dept Biomed & Biol Sci, Karachi 78400, Pakistan

[2] King Saud Univ, Coll Pharm, Dept Pharmacognosy, Riyadh 11495, Saudi Arabia

[3] Morgan State Univ, Sch Comp Math & Nat Sci, Dept Chem, Baltimore, MD 21251 USA

[4] Univ Wisconsin Madison, Dept Bacteriol, Madison, WI 53706 USA

来源：

MOLECULES | 2024年 / 29卷 / 15期

关键词：

oxidative stress; inflammation; advanced glycation end products; receptor for advance glycation end products; antidiabetic compound; GLYCATION END-PRODUCTS; PHOSPHORYLATION; CELLS; ANTIOXIDANT; VIABILITY; RECEPTOR; DISEASE; IRS-1; ASSAY;

D O I：

10.3390/molecules29153649

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The current study intended to investigate the role of new natural compounds derived from the Sesuvium sesuvioides plant in mitigating symptoms of diabetes and insulin resistance in the diabetic mice model. Anti-advanced glycation activity, insulin, and adiponectin were quantified by enzyme-linked immunosorbent assay (ELISA). Glucose uptake was performed using enzymatic fluorescence assay, and glycogen synthesis was measured using PAS staining. Gene and protein expression was assessed using real time PCR (RT-PCR), and immunoblotting and fluorescent microscopy, respectively. The new flavonoid glycoside eupalitin 3-O-alpha-L-rhamnopyranosyl-(1 -> 2)-beta-D-glucopyranoside 1 isolated from S. sesuvioides exhibited anti-AGE activity by reducing human glycated albumin in liver cells. In a diabetic mouse model treated with compound 1, we observed improved glucose tolerance, increased adiponectin levels, and decreased insulin resistance. We also observed alleviated AGEs induced reduction in glucose uptake and restored glycogen synthesis in the compound 1-treated diabetic mice muscles. Exploring the molecular mechanism of action in skeletal muscle tissue of diabetic mice, we found that 1 reduced AGE-induced reactive oxygen species and the inflammatory gene in the muscle of diabetic mice. Additionally, 1 exhibited these effects by reducing the gene and protein expression of receptor for advanced glycation end products (RAGE) and inhibiting protein kinase C (PKC) delta activation. This further led us to demonstrate that compound 1 reduced serine phosphorylation of IRS-1, thereby restoring insulin sensitivity. We conclude that a new flavonoid glycoside from S. sesuvioides could be a therapeutic target for the treatment of symptoms of insulin resistance and diabetes.

引用

页数：16