Dictyota ciliolata ameliorates hyperglycemia, oxidative stress, and inflammation via modulation of metabolic and signaling pathways in diabetic rats.

Diabetes mellitus, marked by chronic hyperglycemia and systemic inflammation, causes oxidative stress and multi-organ damage. Marine macroalgae like Dictyota ciliolata contain polyphenols and flavonoids with potential therapeutic effects on metabolic disorders. This study examined the antidiabetic, hepatoprotective, antioxidant, and anti-inflammatory effects of Dictyota ciliolata extract in alloxan-induced diabetic rats. Adult male Wistar rats were allocated into four groups: normal control, diabetic control, diabetic treated with metformin (5 mg/kg), and diabetic treated with Dictyota ciliolata extract (200 mg/kg) for 21 days. Assessments included fasting blood glucose, serum insulin, liver enzymes (ALT, AST, ALP), lipid profile, oxidative stress biomarkers (MDA, SOD, CAT, GPx), pro-inflammatory cytokines (IL-6, TNF-α), and transcription factors (NF-κB). Gene expression of metabolic regulators (PPAR-γ, GLUT4, IRS-1, Nrf2, AMPK) was analyzed via qRT-PCR. Histopathological examination of the liver and pancreas was conducted to assess tissue-level effects. Treatment with Dictyota ciliolata reduced fasting blood glucose by approximately 38 % and increased serum insulin levels by 55 % compared with diabetic controls. The extract restored liver enzyme profiles and lipid parameters while increasing antioxidant enzyme activities by more than 40 % and significantly reducing lipid peroxidation. Furthermore, the extract modulated the levels of inflammatory cytokines. Gene expression analysis confirmed upregulation of PPAR-γ (0.70-fold), GLUT4 (1.42-fold), AMPK (1.17-fold), IRS-1 (1.36-fold), and Nrf2 (1.49-fold) relative to diabetic controls. Histopathological findings supported the biochemical results, revealing preserved hepatic architecture with limited pancreatic recovery. Dictyota ciliolata ethanolic extract exerts multifaceted protective effects in diabetic conditions via regulation of glycemia, oxidative stress, and inflammatory signaling. These findings highlight its potential as a natural therapeutic candidate for diabetes management.