Combining glycine with thymoquinone offers a promising strategy for diabetes treatment.

Diabetes is increasing globally, and current treatments are frequently associated with high costs and harmful side effects. Researchers are exploring safer, natural alternatives as thymoquinone and glycine. Glycine, the simplest proteinogenic amino acid, and thymoquinone, the active compound in Nigella sativa, have shown promising hypoglycemic, antioxidant, and anti-inflammatory properties. A combination of glycine and thymoquinone for treating diabetes was not investigated before. This work studies the biochemical and histopathological effects of thymoquinone and glycine administered in combination in a diabetic rat model. Diabetes mellitus was induced by streptozotocin (STZ). Five rat groups were used: control healthy, diabetes, diabetic rats treated with glycine (G) or thymoquinone (Q), or the combination (Q + G) groups. Rat body weight changes, water and food intake, fasting blood glucose (FBG), hemoglobin (Hb), glycated Hb (HbA1C), insulin, HOMA-IR, HOMA %B and HOMA %S, QUICKI, albumin, amylase, creatine kinase, TNF-α, IL-10, glucose-6-phosphatase, fructose 1,6-bisphosphatase, glucose-6-phosphat dehydrogenase, oxidative stress portrait, and pancreas histopathology were investigated. Treatment with glycine or thymoquinone or both significantly decreased FBG, oxidative stress, and inflammation and improved metabolic dysfunction compared to untreated diabetic group. It also, revealed cytoprotection to pancreas tissue and reduced inflammatory infiltration. Effects of thymoquinone and glycine treatments were appreciated, however effects of thymoquinone combined with glycine were much better. In conclusion, thymoquinone and glycine combination, can effectively reduce both blood sugar and diabetic-associated complications through their synergistic, strong antioxidant and anti-inflammatory properties, which support the body's natural cytoprotective ability.