A Novel Blend of Momordica charantia and Stevia rebaudiana Extracts Ameliorates Metabolic Dysfunction and Muscle Atrophy in Type 2 Diabetic Mice.

Type 2 diabetes mellitus (T2DM) involves progressive muscle wasting, metabolic dysregulation in peripheral tissues, chronic hyperglycemia, and insulin resistance. Momordica charantia is an antidiabetic agent often limited by bitterness. To improve palatability and efficacy, we developed EMS by combining M. charantia and Stevia rebaudiana (9:1). EMS's antidiabetic effects were tested in streptozotocin (STZ)-induced and genetic db/db mouse models of diabetes. Mice received oral EMS at doses (40, 80, and 120 mg/kg) for six weeks, assessing glucose tolerance, insulin sensitivity, lipid profile, and hepatic markers. Additionally, muscle protein synthesis and degradation mechanisms were analyzed in gastrocnemius tissues. EMS significantly reduced fasting blood glucose and improved insulin sensitivity in both models. EMS decreased liver lipid accumulation and serum ALT and AST levels, indicating hepatic protection. EMS alleviated muscle atrophy by increasing muscle fiber area and was associated with increased expression or activity of AMPK/Sirt1/PGC-1α and IRS-1/PI3K/AKT insulin pathways. It also suppressed FOXO3a-mediated expression of Atrogin-1 and MuRF1, suggesting reduced activation of protein-degradation pathways. Moreover, EMS modulated the gut microbiota, increasing the abundance of beneficial species such as Barnesiella intestinihominis. These findings suggest EMS is a promising multitarget functional ingredient for metabolic complications and musculoskeletal decline in T2DM.