Marmelosin Protects Against Metabolic Disturbances in High-Fat Diet and Streptozotocin-Induced Diabetes

Sattam Khulaif Alenezi,1 Khalid S Alharbi,1 Tariq G Alsahli,2 Reem ALQahtani,3 Muhammad Afzal,4 Krishana Kumar Sharma,5 Nadeem Sayyed6 1Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraydah, Al Qassim, 51452, Saudi Arabia; 2Department of Pharmacology, College of Pharmacy, Jouf University, Sakaka, Aljouf, 72341, Saudi Arabia; 3Department of Pharmaceutical Science, College of Pharmacy, Princess Nourah Bint Abdul Rahman University, Riyadh, Saudi Arabia; 4Department of Pharmaceutical Sciences, Pharmacy Program, Batterjee Medical College, Jeddah, 21442, Saudi Arabia; 5Department of Pharmacology, Teerthankar Mahaveer College of Pharmacy, Teerthankar Mahaveer University, Moradabad, Uttar Pradesh, 244001, India; 6Department of Pharmacology, Dr. R. G. Bhoyar Institute of Pharmaceutical Education and Research, Wardha, Maharashtra, 442001, IndiaCorrespondence: Muhammad Afzal, Email [email protected]: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder indicated by hyperglycemia. The potential for adverse effects occurring in conventional therapies necessitates the exploration of natural alternatives.Aim: This study aimed to evaluate the protective effect of mermelosin in a high-fat diet and streptozotocin (STZ) induced rat model of T2DM.Methods: Twenty-four rats were randomly allocated to four experimental groups (n=6) for a 28-day study. Group 1 served as the control, receiving 0.5 mL of normal saline. Group 2 (T2DM control) received 35 mg/kg STZ and HFD to induce diabetes. Groups 3 and 4 received 10 mg and 20 mg of marmelosin orally, respectively. After 28 days, biochemical analyses were performed to assess pancreatic oxidative stress, insulin levels, and essential biochemical markers, including a lipid profile, liver function, inflammatory responses, oxidative stress levels, and apoptotic activity.Results: Marmelosin significantly improved fasting blood glucose (FBG) and hemoglobin A1c (HbA1c) levels in rats with T2DM. It also enhanced insulin sensitivity, as evidenced by increased plasma insulin levels and decreased HOMA-IR values. Marmelosin effectively mitigated dyslipidemia by lowering total cholesterol and serum triglycerides while elevated HDL cholesterol. Furthermore, it acted as a potent antioxidant, as indicated by the elevation of SOD, GSH, CAT, and reduced cytokines (TNF-α, IL-1β, IL-6). Marmelosin also reduced apoptosis by downregulating caspase-3 expression.Conclusion: These findings collectively suggest that marmelosin acts as a multifaceted protective effect, including metabolic regulation, anti-inflammatory, antioxidant, and anti-apoptotic activities, highlighting its potential as a promising therapeutic agent for the management of T2DM. Keywords: high-fat diet, marmelosin, streptozocin, type II diabetes