In vitro evaluation of antidiabetic potential of hesperidin and its aglycone hesperetin under oxidative stress in skeletal muscle cell line

Abstract

The present study investigates the in vitro antidiabetic and antioxidant potential of hesperidin and hesperetin under oxidative stress induced in L6 myotubes. Also, the study attempts to reveal the effect of glycosylation (hesperetin) on the biological activities of hesperidin. Oxidative stress is the leading cause of complications associated with diabetes. Both hesperidin and hesperetin reduce oxidative stress directly by scavenging intracellular reactive oxygen species (ROS) and by up-regulating natural antioxidant defence system like glutathione. Hesperidin and hesperetin at 10μM inhibited the non-enzymatic glycation of proteins (65.57% and 35.6%, respectively), the critical reaction involved in the formation of advanced glycation end products (AGEs) which has a significant role in the pathogenesis of diabetes. Additionally, these compounds induced glucose uptake in L6 myotubes following acute and chronic treatment. The percentage 2-NBDG uptake shown by both the compounds was comparable with that of the antidiabetic drug, rosiglitazone (30.4%). Both the compounds downregulated PI3 kinase activity whereas GLUT4, IRS, and AKT were upregulated in L6 myotubes pointing to the possible overlapping with the insulin signalling pathway.Significance of the study: Evidence suggest that oxidative stress occurs in diabetes and could have a role in the development of insulin resistance. Oral hypoglycaemic agents which target on increasing insulin levels and improving insulin sensitivity or that reduce the rate of carbohydrate absorption from the gastrointestinal tract are used to manage type 2 diabetes. But these therapies rarely target the real cause of type 2 diabetes and have severe adverse effects. The observations from the present study provide significant evidence for hesperidin and hesperetin, to be considered as a dietary supplement to manage type 2 diabetes and to suppress oxidative stress mediated diabetic pathophysiology.

Deteriorating insulin resistance due to WL15 peptide from cysteine and glycine‐rich protein 2 in high glucose‐induced rat skeletal muscle L6 cells

“…Lipid peroxidation in cells occurs due to oxidative damage and is a direct marker for oxidative stress. Lipid peroxidation was analyzed with the thiobarbituric acid method with slight modification (Dhanya & Jayamurthy, 2020). In brief, after WL15 pretreatment, the L6 myotube cells were washed with phosphate-buffered saline (PBS) and homogenized.…”

Citrus species: Modern functional food and nutraceutical-based product ingredient

“…Recently, hesperetin showed cellular antioxidant activity with a value of 23.57 μmol of QE/100 μmol (Huang et al, 2020). Both hesperidin and hesperetin were able to reduce oxidative stress directly by scavenging intracellular ROS and increase natural antioxidant defense system with particular reference to glutathione (Dhanya and Jayamurthy, 2020). In addition, these flavonoids inhibited the non-enzymatic glycation of proteins involved in the formation of advanced glycation end-products which have an important role in developing diabetes.…”

Natural Drugs as a Treatment Strategy for Cardiovascular Disease through the Regulation of Oxidative Stress

“…Hesperidin is a flavonoid widely found in lemon or citrus fruits and has strong antioxidant activity [ 74 ]. Hesperidin has been reported to have a wide range of pharmacological effects, such as regulation of lipid metabolism abnormalities, protection of cardiovascular endothelial cells, antioxidant activity, and regulation of autophagy [ 75 , 76 ]. Research shows that hesperidin can inhibit oxidative stress by regulating Nrf2/ARE/HO-1 and TGF-beta1/Smad3 signal transduction [ 77 ].…”