Pharmacological Study of <em>Amaranthus spinosus</em> L. Root Extract on High-Fat Diet and Low-Dose Streptozocin-Induced Type 2 Diabetes Complications in Rats

Diabetes complications appear with the severity of hyperglycemia and the age of the disease. In type 2 diabetes mellitus (T2DM), herbal medicines are also effective in reducing hyperglycemia and can be used for this purpose to manage complications. This study aimed to prove the effectiveness of Amaranthus spinosus root extract on type 2 diabetes (T2D) and its microvascular complications. A high-fat diet and low-dose streptozocin were used for 20 days to induce T2D syndrome and complications in rats. The validated animal models were treated orally with the dried hydroethanolic extract of A. spinosus for three weeks; then the hematological, biochemical, and histological markers were evaluated. The results showed that the extract at a dose of 500 mg/kg bw was effective against diabetes and its complications. This effectiveness was linked to a significant reduction (p &amp;lt; 0.0001) in basal blood glucose, tissue oxidative stress, serum cardiovascular and hepato-renal markers, and an improvement in insulin secretion and utilization. The protective activity of the extract against macular edema and renal fibrosis was confirmed by histopathological examinations. These findings prove that A. spinosus root extract contains bioactive compounds that may be useful in preventing or reversing diabetic retinopathy and renal fibrosis.