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

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
• streptozotocin
• antioxidant
• anti-inflammatory
• docking study

Acknowledgments

Authors would like to acknowledge the support of the Deputy for Research and Innovation Ministry of Education, Kingdom of Saudi Arabia for this research through a grant (NU/IFC/02//MRC/-004) under the Institutional Funding Committee at Najran University, Kingdom of Saudi Arabia. Also, the authors would like to thank CPCSEA-Institutional Animal Ethics Committee, TRS lab, Maharashtra, India, Animal ethical Activity allotted number - IAEC/05/23 for their research support.

Authors’ contributions

Conceptualization and fund acquisition: Hassan H Almasoudi; Mohammed H Nahari; Methodology and first draft of manuscript: Hassan H Almasoudi; Farhan R. Khan; Critical Revision of manuscript: Hassan H Almasoudi; Abdulkarim S. Binshaya; Mohammed Ageeli Hakami; Abdulfattah Yahya M. Alhazmi; Humood Al Shmrany; Abdullah Alqasem.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

All the data generated in this study have been included in the manuscript.

Additional information

Funding

The authors declare financial support was received for the research, authorship, and/or publication of this article. This research was funded by the Deputy for Research and Innovation Ministry of Education, Kingdom of Saudi Arabia for this research through a grant (NU/IFC/02//MRC/-004) under the Institutional Funding Committee at Najran University, Kingdom of Saudi Arabia.