Perilla frutescens Seed Residue Extract Restores Gut Microbial Balance and Enhances Insulin Function in High-Fat Diet and Streptozotocin-Induced Diabetic Rats

The seed residue of <i>Perilla frutescens</i> possesses diverse biological properties and is rich in bioactive phytochemicals, including luteolin, rosmarinic acid, and apigenin. The aim of this study was to investigate the anti-diabetic effects of perilla seed residue crude extract (PCE) and its impact on the composition of the gut microbiome in rats with diabetes induced by a high-fat diet (HFD) and streptozotocin (STZ). Forty male Wistar rats were fed on an HFD for six weeks before receiving an injection of STZ injection to induce diabetes. These rats were then treated for four weeks with metformin (100 mg/kg bw) or PCE (100 and 1000 mg/kg bw) alongside a control group maintained on a normal diet. The results showed that PCE treatment improved metabolic parameters in diabetic rats, as evidenced by reduced water and food intake, increased body weight gain, lower blood glucose levels, and enhanced insulin secretion effects, especially at the 100 mg/kg bw dosage. PCE also promoted the regeneration of pancreatic β-cells and improved utilization of glucose. PCE also suppressed inflammation and oxidative stress, enhanced antioxidant capacity, and reduced circulating triglyceride levels. Most notably, PCE administration increased gut microbial diversity and shifted the microbiome closer to that of healthy controls, demonstrating its prebiotic effect. It promoted the abundance of beneficial bacteria that are linked to improved glucose metabolism and reduced inflammation-specifically, <i>Bacteroides fragilis</i>, <i>Lactobacillus</i>, <i>Clostridium</i>, and <i>Akkermansia.</i> Harmful bacteria associated with inflammation and poor glycemic control were reduced. Collectively, these results suggest that PCE not only helps restore a balanced gut microbiome but also offers metabolic benefits that could improve diabetic outcomes. These findings position PCE as a promising supplement for the management of diabetes and encourage further exploration of the mechanisms associated with its actions.