Hypoglycemic Effect of Pleurotus citrinopileatus and Hericium erinaceus Buccal Tablets on Diabetic Mice

Diabetes mellitus poses a global health challenge, necessitating natural adjuvants with minimal side effects. The aims of this study were to optimize the concentrations of chromium (Cr), zinc (Zn), and germanium (Ge) in the liquid fermentation media of <i>Pleurotus citrinopileatus</i> and <i>Hericium erinaceus</i> and to evaluate the hypoglycemic efficacy of buccal tablets in diabetic mice. The results showed that the optimal ion concentrations in the liquid fermentation medium were Cr 200 mg/L, Zn 200 mg/L, and Ge 50 mg/L for <i>P. citrinopileatus</i>, and Cr 200 mg/L, Zn 100 mg/L, and Ge 100 mg/L for <i>H. erinaceus</i>. After 3 weeks of administration of high-dose (6 g/kg) <i>P. citrinopileatus</i> and <i>H. erinaceus</i> buccal tablets, a 29.1% reduction in the blood glucose levels of diabetic mice was observed compared with pre-administration. High-dose tablets decreased the levels of total cholesterol, triglyceride, and low-density lipoprotein cholesterol while increasing high-density lipoprotein cholesterol. Compared with negative control, high-dose tablets increased catalase and superoxide dismutase activities by 31.2% and 34.1%, respectively. Moreover, the buccal tablets modulated the diversity and structure of the gut microbiota in mice. Relative abundance of beneficial genera (<i>Lactobacillus</i>, <i>Akkermansia</i>, <i>Bifidobacterium</i>, and <i>Ruminococcus</i>) in the high-dose group were increased, while diabetogenic taxa (<i>Prevotella</i>, <i>Desulfovibrio</i>, and <i>Enterococcus</i>) were inhibited. It is concluded that buccal tablets combining <i>P. citrinopileatus</i> and <i>H. erinaceus</i> treated with Cr, Zn, and Ge significantly ameliorated hyperglycemia, dyslipidemia, and oxidative stress, and reshaped the gut microbiota in diabetic mice, demonstrating the potential of edible mushrooms and trace elements as a natural antidiabetic therapy.