The Effect of Crocus Sativus (Saffron) on the Liver Histology in Diabetic Rats Induced by a High-Fat High-Glucose Diet and Low Dose of Streptozotocin

Diabetes mellitus (DM) contributes to hepatic dysfunction through oxidative stress, inflammation, and insulin resistance. To address its prevalence, Crocus sativus L. (saffron) stigma contains antioxidant and hepatoprotective compounds. Therefore, this study aims to examine the effect of saffron ethanol extract on liver function and histological features in rats with DM. A total of 17 male Wistar rats were divided into 4 groups, namely K– (non-diabetic control, n=4), Kd (diabetic control, n=5), P1 (diabetic+saffron 20 mg/kgBW, n=4), and P2 (diabetic+saffron 60 mg/kgBW, n=4). From weeks 1-12, K– received a standard diet, while Kd, P1, and P2 received a high-fat high-glucose diet (HFHGD). Diabetes was then induced at week 4 in Kd, P1, and P2 through intraperitoneal administration of streptozotocin (35 mg/kgBW). K– and Kd received distilled water, while P1 and P2 were treated with saffron ethanol extract from weeks 9-12. Flavonoids, alkaloids, tannins, and saponins were identified through phytochemical analysis. At week 12, the animals were sedated for blood collection and then euthanized for liver sampling. Liver weight, serum levels of aspartate aminotransferase, alanine aminotransferase, and cholesterol were assessed. Liver histology was assessed semiquantitatively. Kd group showed significantly increased liver weight (p=0.002) and cholesterol (p<0.001) compared to K–. In addition, P2 showed reduced cholesterol (p<0.01vs Kd) and histological improvements. Aspartate and alanine aminotransferase levels decreased nonsignificantly (p>0.05). These findings suggest that saffron stigma extract can exert notable hepatoprotective effects in rats induced with DM, particularly in cholesterol reduction and histological improvements.