In silico Docking Studies of Antiglycation Activity of Isorhamnetin on Molecular Proteins of Advanced Glycation end Product (AGE) Pathway

Abstract

Advanced glycation end products (AGEs) are formed excessively in pathological conditions due to non - enzymatic glycation of proteins, lipids or nucleic acids, affecting their structure and function. Isorhamnetin is a naturally occurring flavonoid with anti-inflammatory, anti-oxidant, anti-obesity, anticancer, anti-diabetic and anti-atherosclerosis activity. Structure activity studies of isorhamnetin reveal the presence of hydroxyl group in the B-ring of isorhamnetin may contribute to antiglycation activity. Hence we hypothised that isorhamnetin may have antiglycation activity owing to its structure as well as antioxidant and free radical scavenging activities by modulating various AGE pathway proteins. The aim of our study was to determine the antiglycation activity of isorhamnetin by targeting various molecular proteins of AGE pathway using insilico docking. The structure of isorhamnetin was imported and drawn in Marvin sketch (version 6. 3. 0). Nearly 17 molecular proteins of AGE pathway were docked with isorhamnetin using autodock tools 4.2 (version 1. 5. 6) software. The present study showed that isorhamnetin exhibited good docking profiles with receptor for advanced glycation End product (RAGE), protein kinase B (PKB/Akt2), activating transcription factor4 (ATF4), cAMP response element-binding protein (CREB), extracellular signal regulated kinase (ERK), phosphatidylinositol 3-kinase (PI3-K) and signal transducer and activator of transcription (STAT) indicating it may exert good antiglycation activity by modulating these proteins of AGE pathways. However further invitro and invivo studies are required to establish the antiglycation activity of isorhamnetin.

Preliminary evaluation of the antiglycoxidant activity of verapamil using various in vitro and in silico biochemical/biophysical methods

“…The action of transcription factors leads to insulin resistance, inflammation, oxidative stress, apoptosis, and also autophagy. In diabetes, AGEs-RAGE signaling is overexpressed, which is a direct cause of diabetic complications ( Pathomthongtaweechai and Chutipongtanate, 2020 ; Shen et al, 2020 ; Sindhuja et al, 2021 ) ( Figure 2 ). Verapamil showed satisfactory affinity (no lower than −4.6 kcal/mol) for all seventeen proteins, possibly restoring their initial physiological function.…”

“…This promotes inflammation, oxidative stress, and structural changes in blood vessels, ultimately leading to complications such as atherosclerosis, nephropathy, retinopathy, and impaired vascular function. A molecular docking for AGE pathway proteins revealed that verapamil may owe its antiglycative properties in vivo ( Pathomthongtaweechai and Chutipongtanate, 2020 ; Shen et al, 2020 ; Sindhuja et al, 2021 ). The drug presented a good docking ability to all tested ligands, starting at −4.6 kcal/mol for ATF4.…”

“…We utilized the PyMOL 2.5 program to visualize the molecular docking results. This allowed us to examine the binding interactions between proteins and verapamil at the molecular level ( Oso and Olaoye, 2020 ; Sindhuja et al, 2021 ; Nesterowicz et al, 2023a ; Nesterowicz et al, 2023b ).…”

Novel Properties of Old Propranolol─Assessment of Antiglycation Activity through In Vitro and In Silico Approaches

“…The exhaustiveness parameter was set at a level of 8. Finally, PyMOL 2.5 allowed us to visualize the possible molecular docking. ,− ,− …”

Antidiabetic Molecular Mechanisms of Active Compounds from Several Orchids

“…Another mechanism of action of antiglycation compounds is by binding to their receptors, this can cause cellular mechanisms due to the interaction of AGEs with their receptors to be inhibited (Sindhuja et al, 2021). Orchids also contain polyphenols, such as Bauhinia variegate (Abdel-Halim et al, 2020).…”