Gymnema sylvestre (GS) has been traditionally used to treat diabetes mellitus (DM) and consumed as both food and medicine. The present work aimed to reveal the arresting hypoglycemic properties of GS leaves on type 2 DM (T2DM) rats meditated by gut microbiota pathway. After administration for 30 days, GS treatment observably improved the abnormal fasting blood glucose (FBG) levels, lipid profiles, and the glucose tolerance of the T2DM rats in a dose-dependent manner. Furthermore, GS treatment reversibly restored the gut microbiota diversities in the T2DM rats based on the decreased Firmicute abundance and boosted Bacteroidetes abundance and Firmicutes/Bacteroidetes ratio. Particularly, the KEGG pathway suggested that GS treatment strongly interfered with the glucose metabolism processes, such as the glycolysis from glucose 6-phosphate and glucose, along with the changes in the relative abundances of the beneficial bacteria of Clostridium , Lactobacillus , and Bacteroides . In addition, the GS treatment dramatically promoted the contents of the acetic acid, the total short-chain fatty acids in the T2DM rat feces. This study showcased the remarkable amelioration of GS on the metabolic disorders of blood glucose and lipids via the regulation of gut microbiota in T2DM rats, which could offer a new mechanism of GS as a potential natural antidiabetic food supplement for T2DM.
Chronic wound healing remains a persistent challenge clinically, particularly in diabetic wounds, where hyperglycemia drives sustained activation of the AGE-RAGE-associated signaling within the wound bed, precipitating excessive ROS generation and persistent inflammation that together stall tissue repair and erode quality of life. To address this, we developed a core-shell microneedle (GS + IL-4@MN) patch loading Gymnema sylvestre (GS) extract and interleukin-4 (IL-4) as a promising therapeutic strategy. The patch comprised a 10 × 10 array of conical needles and the optimized shell-loading concentration of GS was determined to be 1.0 mg/mL. The GS-loaded outer shell can suppress the release of pro-inflammatory mediators, scavenge ROS, and strengthen antioxidant defenses, thereby attenuating local inflammation; the IL-4-encapsulated core induces macrophage polarization toward the M2 phenotype, mitigates the pro-inflammatory microenvironment, and modulates T-cell immunity, while enhancing cellular proliferation and migration to support tissue regeneration. In diabetic wound models, GS + IL-4@MN achieved wound-closure rates of 64.72 ± 6.3% at day 3 and 85.80 ± 3.6% at day 7, and re-epithelialization reached 91.52 ± 2.1% by day 14. Moreover, collagen deposition increased to 79.38 ± 4.3%, CD31-positive neovascularization reached 70.50 ± 3.7%, and the M1/M2 ratio decreased to 0.3, indicating marked inflammatory resolution and regenerative activation. In summary, this core-shell MN system achieves multidimensional regulation of the pathological microenvironment of diabetic wounds through a dual mechanism: outer-layer inflammatory suppression and inner-layer microenvironment reset, and offers a new avenue for promoting diabetic wound healing.
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