| Summary: | We recently reported that varying combination ratios of lemon balm (<i>Mellissa officinalis</i> L.) and corn silk extracts (Stigma of <i>Zea mays</i> L. fruit) could reduce the obesity caused by a high-fat diet (HFD). The present study investigated the dose-dependent effect of a 1:1 (<i>w</i>:<i>w</i>) mixture of lemon balm and corn silk extracts (M-LB/CS) on HFD-mediated metabolic disorders and compared the effect with metformin. Oral administration of 50–200 mg/kg of M-LB/CS for 84 days significantly inhibited HFD-induced body weight gain, adipocyte hypertrophy, and lipogenic gene induction without affecting food consumption in mice. Biochemical analyses showed that M-LB/CS blocked abnormal lipid accumulation in the blood by escalating fecal lipid excretion. In addition, M-LB/CS prevented HFD-mediated pancreatic atrophy, decreased the number of insulin- and glucagon-immunoreactive cells, and inhibited increases in glycated hemoglobin, glucose, and insulin. Moreover, M-LB/CS also reduced hepatic injury, lipid accumulation, gluconeogenesis, and lipid peroxidation in parallel with the induction of AMP-activated protein kinase and antioxidant enzymes. Furthermore, M-LB/CS protected the kidney by inhibiting tubular vacuolation and reducing serum creatinine and blood urea nitrogen levels. The prophylactic effect of 100 mg/kg M-LB/CS-administration was comparable to that of metformin. Therefore, M-LB/CS may be an alternative option for managing obesity and its related metabolic disorders.
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