Therapeutic Potential of Holothuria leucospilota Extract in STZ-Induced Diabetic Rats: Targeting Inflammation and Apoptosis at the Gene Expression Level.

INTRODUCTION: Chronic inflammation is a key contributor to diabetes pathogenesis. Marine-derived bioactive compounds offer a promising source of therapeutic agents. This study investigated the effects of Holothuria leucospilota n-hexane extract on biochemical and inflammatory markers in diabetic male rats. MATERIALS AND METHODS: Male Wistar rats were divided into four groups: control, diabetic, and diabetic treated with H. leucospilota extract (100 or 200 mg/kg). Diabetes was induced by streptozotocin. Animals received daily intraperitoneal injections of saline or extract. One-third of the animals in each group (n = 8) were euthanised and sampled on days 1, 15, and 30. The extract composition was analysed by GC-MS. Serum glucose, insulin, amyloid beta, and expression of TGF-β, TNF-α, FasL, IL-10, and miR-146a were measured in blood, while leptin gene expression was assessed in liver samples. RESULTS: GC-MS revealed major compounds including olean-12-ene-3,28-diol (14.1%), cyclohexane derivatives (8.2%), oleic acid (4.8%), and cis-13-eicosenoic acid (4.2%). Diabetic rats showed elevated glucose, amyloid beta, leptin, TGF-β, TNF-α, and FasL levels, with reduced insulin, IL-10, and miR-146a levels compared to the control group. Treatment with H. leucospilota extract (100 and 200 mg/kg) significantly reversed these changes at both 15 and 30 days compared to the diabetic group. CONCLUSION: H. leucospilota n-hexane extract improved biochemical and inflammatory markers in diabetic rats, suggesting its potential as a natural therapeutic agent to mitigate diabetes-associated inflammation and metabolic dysfunction. The identified bioactive compounds may underlie these beneficial effects, highlighting the therapeutic relevance of marine-derived extracts in diabetes management.