We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Assessment of the dual role of Lyonia ovalifolia (Wall.) Drude in inhibiting AGEs and enhancing GLUT4 translocation through LC-ESI-QTOF-MS/MS determination and in silico studies.
- Authors
Sahu, Neha; Singh, Nitesh; Arya, Kamal Ram; Reddy, Sabbu Sathish; Rai, Amit Kumar; Shukla, Vijaya; Pandey, Jyotsana; Narender, Tadigoppula; Tamrakar, Akhilesh Kumar; Kumar, Brijesh; Rajak, Bikash Kumar; Malik, Sumira; Rustagi, Sarvesh
- Abstract
Introduction: Diabetes mellitus (DM) is a metabolic disorder that results in glucose accumulation in the blood, accompanied by the production of advanced glycation end products (AGEs) through glycation of cellular proteins. These AGEs interfere with insulin signaling and prevent GLUT4 membrane translocation, thereby promoting the accumulation of more glucose in the blood and causing post-diabetic complications. Methods: In this study, we examine the anti-diabetic potential of Lyonia ovalifolia (Wall.) Drude, a well-known ethnomedicinal plant of the Indian Himalayas. Considering its various medicinal properties, we analyzed its ethanolic extract and various solvent fractions for in vitro antiglycation activity and antidiabetic potential, i.e., stimulation of GLUT4 translocation. Result and Discussions: The results showed that the extract and fractions exhibited increased antiglycation activity and an increased level of GLUT4 translocation. Analysis of a further 12 bioactive compounds of ethanolic extract, identified through LC-ESI-QTOF-MS/MS, revealed the presence of three new compounds: leucothol B, rhodoterpenoids A, and leucothol A. Moreover, we performed molecular docking of identified compounds against key proteins of diabetes mellitus: the sirtuin family of NAD (+)-dependent protein deacetylases 6 (SIRT6), aldose reductase (AR), and tyrosine kinase (TK). The results showed that flavonoid luteolin showed the best binding affinity ((−12.3 kcal/mol), followed by eriodictyol, astilbin, and syringaresinol. An ADMET study showed that luteolin, eriodictyol, astilbin, and syringaresinol may be promising drug candidates belonging to the flavonoid class of compounds, with no harmful effects and complying with all the drug-likeness guidelines. Furthermore, molecular dynamics (MD) simulations on a 50 ns timescale revealed that AR protein was most stable with luteolin throughout the simulation period. Therefore, this study reveals for the first time that L. ovalifolia plays an important role in insulin homeostasis, as shown in in vitro and in silico studies.
- Subjects
SIRTUINS; NAD (Coenzyme); ADVANCED glycation end-products; BLOOD sugar; ALDOSE reductase; MOLECULAR dynamics; PROTEIN-tyrosine kinases
- Publication
Frontiers in Pharmacology, 2023, Vol 14, p1
- ISSN
1663-9812
- Publication type
Article
- DOI
10.3389/fphar.2023.1073327