Sakuranetin ameliorates streptozotocin-induced diabetes in rodents by inhibiting caspase-3 activity, modulating hematological parameters, and suppressing inflammatory cytokines: a molecular docking and dynamics study

Hassan H Almasoudi; Mohammed H Nahari; Abdulkarim S Binshaya; Mohammed Ageeli Hakami; Abdulfattah Y Alhazmi; Humood Al Shmrany; Abdullah Alqasem; Farhan R Khan

doi:10.1080/07391102.2024.2325659

Sakuranetin ameliorates streptozotocin-induced diabetes in rodents by inhibiting caspase-3 activity, modulating hematological parameters, and suppressing inflammatory cytokines: a molecular docking and dynamics study

J Biomol Struct Dyn. 2024 Mar 9:1-18. doi: 10.1080/07391102.2024.2325659. Online ahead of print.

Authors

Hassan H Almasoudi¹, Mohammed H Nahari¹, Abdulkarim S Binshaya², Mohammed Ageeli Hakami³, Abdulfattah Y Alhazmi⁴, Humood Al Shmrany², Abdullah Alqasem², Farhan R Khan⁵

Affiliations

¹ Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Najran University, Najran, Saudi Arabia.
² Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Alkharj, Saudi Arabia.
³ Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Al-Quwayiyah, Shaqra University, Riyadh, Saudi Arabia.
⁴ Pharmaceutical Practices Department College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia.
⁵ Department of Pharmaceutical Chemistry, P. W College of Pharmacy, Yavatmal, India.

PMID: 38459941
DOI: 10.1080/07391102.2024.2325659

Abstract

Diabetes affects people of all ages, regardless of gender and background. To date, there is no evidence for the effect of sakuranetin against the streptozotocin (STZ)-induced diabetes paradigm. The research was directed to evaluate the antidiabetic activity of sakuranetin in the STZ model invoking the diabetes-induced disease paradigm. STZ (I.P. 60 mg/kg) is directed to induce type 2 diabetes in experimental rats. Recent research pursued to regulate the anti-diabetic ability of sakuranetin at both 10 and 20 mg/kg in STZ-induced rats. Furthermore, molecular docking research was implemented to evaluate sakuranetin requisite attraction to inflammatory indicators. Various anti-diabetic [(glucose, hemoglobin A1c (HbA1c), and insulin)], lipid profile [triglycerides (TG), total cholesterol (TC), and high-density lipoproteins (HDL)], hematological parameters [Hemoglobin (HGB), packed cell volume (PCV), red blood cells (RBC), mean corpuscular volume (MCV), platelet (PLT), and white blood cells (WBC), pro-inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6)], antioxidant level [catalase (CAT), superoxide dismutase (SOD), glutathione (GSH)], lipid oxidation, and caspase-3 were evaluated. Furthermore, molecular docking and dynamics were performed for TNF-α (2AZ5), IL-6 (1ALU), IL-1β (6Y8M), Caspase-3 (1NME) and serum insulin (4IBM) target ligands. Sakuranetin treatment at both doses restored the biochemical parameters i.e. blood glucose, insulin, HbA1c, lipid profile, hematological parameters, pro-inflammatory markers, antioxidant levels, lipid oxidation, and caspase-3 in the context of diabetic rats. It also showed favorable binding affinity on inflammatory markers. Sakuranetin binds to proteins 2AZ5, 1ALU, 6Y8M, 1NME, and 4IBM at -7.489, -6.381, -6.742, -7.202, and -8.166 Kcal/mol, respectively. All of the findings from the molecular dynamics simulations points toward a considerable change in the conformational dynamics of protein upon binding with sakuranetin. The potential use of sakuranetin as an alternative diabetes medication will aid future research as a potent anti-diabetic agent.Communicated by Ramaswamy H. Sarma.

Keywords: Sukuranetin; anti-inflammatory; antioxidant; docking study; streptozotocin.