MELHAC Improves Glucose and Lipid Metabolism in HFD + Alloxan-Induced Mice

Background: Glucose and lipid metabolism disorders are characterized by hyperglycemia, dyslipidemia, hepatic oxidative stress, lipid accumulation, and gut microbiota dysbiosis, all of which contribute to progressive metabolic dysfunction and tissue injury. As a plant extract mixture derived from mulberry leaves, lotus leaves, and Eucommia leaves, MELHAC (Mulberry–Eucommia–Lotus Herbal Aqueous Complex) was developed as a medicinal and edible formula with potential multi-component metabolic regulatory activity. In the present study, we systematically evaluated the effects of MELHAC on glucose and lipid metabolic abnormalities in high-fat diet (HFD) plus alloxan-induced mice. Methods: The phytochemical profile of MELHAC was characterized using untargeted LC–MS and network pharmacology. Its metabolic effects were evaluated in HFD plus alloxan-induced mice by measuring fasting blood glucose, serum lipid parameters, glucose tolerance, hepatic oxidative stress markers, histopathological changes, hepatic lipid accumulation, gut microbiota composition, and preliminary safety indices. Results: Chemical characterization revealed that MELHAC contains abundant bioactive constituents dominated by flavonoids, phenolic acids and alkaloids. In vivo experiments demonstrated that MELHAC lowered fasting blood glucose, total cholesterol and triglyceride levels, while ameliorating glucose intolerance and pathological damage in the liver, kidney and pancreas. MELHAC also improved liver-related biochemical abnormalities, increased hepatic superoxide dismutase, decreased malondialdehyde, and reduced hepatic lipid accumulation, indicating protective effects against oxidative stress and steatosis associated with metabolic dysfunction. In addition, MELHAC modulated gut microbial community structure and differential taxa linked to metabolic homeostasis. Short-term high-dose administration did not cause obvious abnormalities in serum biochemical, hematological, or histopathological indices. Conclusions: These findings suggest that MELHAC has potential as a plant-derived functional ingredient for improving glucose and lipid metabolic disorders and may provide an experimental basis for the future development of functional foods targeting metabolic health.