Thymoquinone attenuates diabetes-induced hepatic damage in rat via regulation of oxidative/nitrosative stress, apoptosis, and inflammatory cascade with molecular docking approach

• Published in: Scientific reports Vol. 14; no. 1; pp. 13016 - 20
• Main Authors: Hafez, Mona H., Ez Elarab, Samar M., Tohamy, Hossam G., El-Far, Ali H.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 06.06.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 631/45; 692/308; Animals; Antioxidants; Antioxidants - metabolism; Antioxidants - pharmacology; Apoptosis; Apoptosis - drug effects; Benzoquinones - pharmacology; Beta cells; Blood Glucose - metabolism; Body weight; Caspase-3; Cytochrome P450; Cytokines; Diabetes; Diabetes mellitus; Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Experimental - metabolism; Down-regulation; Enzymatic activity; Glucose-6-phosphatase; Humanities and Social Sciences; Hyperglycemia; Hyperlipidemia; Inflammation; Inflammation - drug therapy; Inflammation - metabolism; Interleukin 1; Interleukin 6; Lipid peroxidation; Liver; Liver - drug effects; Liver - metabolism; Liver - pathology; Male; Molecular docking; Molecular Docking Simulation; multidisciplinary; Nitric oxide; Nitrosative Stress - drug effects; Oral administration; Oxidative stress; Oxidative Stress - drug effects; p53 Protein; Peroxidation; Pro-inflammatory cytokines; Rats; Rats, Wistar; Science; Science (multidisciplinary); Streptozocin; Streptozotocin; Thymoquinone; Tumor necrosis factor receptors; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Pro-inflammatory cytokines; Oxidative stress; Streptozotocin; Molecular docking; Thymoquinone
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-62780-y

Diabetes mellitus (DM) is a complex metabolic condition that causes organ dysfunction. The current experiment sought to determine the effect of thymoquinone (TQ) on hyperglycemia, hyperlipidemia, oxidative/nitrosative stress, inflammation, and apoptosis in diabetic rats prompted by streptozotocin (STZ) (55 mg/kg body weight i/p). The animals were allocated into control, TQ (50 mg/kg B.W. orally administered for 4 succeeding weeks), Diabetic, and Diabetic + TQ groups. This study confirmed that TQ preserves the levels of insulin, fasting blood glucose, HOMA β -cell indices, HbA1c %, body weight, and lipid profile substantially relative to the DC group. Furthermore, hepatic antioxidant (CAT, GSH, and T-SOD) values were reduced. Conversely, the enzymatic activity of liver functions (AST, ALT, ALP, cytochrome P450, and hepatic glucose-6-phosphatase), lipid peroxidation (MDA), pro-inflammatory cytokines (IL-1 β , TNF- α , and IL-6), nitric oxide (NO) and inflammatory marker (CRP) enhanced with STZ administration, which is substantially restored after TQ treatment. Relative to the diabetic rats, TQ reestablished the hepatic architectural changes and collagen fibers. Additionally, TQ downregulated the intensity of the immunohistochemical staining of pro-apoptotic marker (caspase-3), p53, and tumor necrosis factor-alpha (TNF- α ) proteins in hepatic tissues. Furthermore, TQ displayed abilities to interact and inhibit the binding site of caspase-3, interleukin-6 receptor, interleukin-1 receptor type 1, TNF receptor superfamily member 1A, and TNF receptor superfamily member 1B in rats following the molecular docking modeling. All these data re-establish the liver functions, antioxidant enzymes, anti-inflammatory markers, and anti-apoptotic proteins impacts of TQ in STZ-induced DM rats. Founded on these outcomes, the experiment proposes that TQ is a novel natural supplement with various clinical applications, including managing DM, which in turn is recommended to play a pivotal role in preventing the progression of diabetes mellitus.