Green Biosynthesis of Bioactive Streptomyces Metabolites Using Edible Mushrooms: Implications for Glycemic Control and Hepatic Protection in Diabetic Rats

Diabetes mellitus is characterized by chronic hyperglycemia and oxidative stress, frequently leading to hepatic dysfunction. Functional food–based strategies that offer glycemic regulation and organ protection are increasingly sought as safer alternatives to long‐term pharmacotherapy. This study explored the green biosynthesis of Streptomyces secondary metabolites using edible mushrooms and evaluated their potential for glycemic control and hepatic protection in diabetic rats. A Streptomyces isolate was molecularly identified by 16S rRNA sequencing and cultivated using Pleurotus ostreatus extract as a biological mediator for metabolite biosynthesis. Phytochemical composition and antioxidant activity were assessed in vitro. Streptozotocin‐induced diabetic rats were treated orally with biosynthesized metabolite extracts (200 and 400 mg/kg). Fasting blood glucose, liver function enzymes, hepatic oxidative stress markers, histopathology, and molecular docking against diabetes‐related targets were evaluated. The biosynthesized extract contained high levels of total phenolics (68.42 ± 3.15 mg GAE/g) and flavonoids (41.76 ± 2.08 mg QE/g), with strong DPPH scavenging activity (~81%). High‐dose treatment reduced fasting blood glucose from > 300 to 129.6 ± 11.8 mg/dL by Day 28. Serum ALT, AST, and ALP levels were significantly lowered compared to diabetic controls, while hepatic malondialdehyde decreased from 4.92 ± 0.41 to 2.18 ± 0.21 nmol/mg protein. Molecular docking revealed strong binding affinities against α‐glucosidase (−10.9 kcal/mol) and oxidative stress–related proteins (−7.9 kcal/mol). Edible mushroom–mediated biosynthesis of Streptomyces metabolites produced a bioactive extract with significant glycemic regulatory, antioxidant, and hepatoprotective effects, supporting its potential application as a functional food or nutraceutical for metabolic health management.