The herbal extract ALS-L1023 from Melissa officinalis reduces weight gain, elevated glucose levels and β-cell loss in Otsuka Long-Evans Tokushima fatty rats

J Ethnopharmacol. 2021 Jan 10;264:113360. doi: 10.1016/j.jep.2020.113360. Epub 2020 Sep 9.


Ethnopharmacological relevance: Melissa officinalis L. (Labiatae; lemon balm) is a traditional medicinal plant with hypoglycemic and hypolipidemic effects; however, how it imparts its beneficial effects remains unclear. We thus hypothesized that the herbal extract ALS-L1023, isolated from Melissa officinalis, inhibits obesity and diabetes, and tested our hypothesis using Otsuka Long-Evans Tokushima fatty (OLETF) rats, which are an established animal model of type 2 diabetes.

Materials and methods: In this study, 28-week-old OLETF rats were fed a high-fat diet for 4 weeks to induce a marked impairment of the insulin response and were treated with or without ALS-L1023. Subsequently, the variables and determinants of glucose metabolism and pancreatic function were assessed via blood analysis, histology, immunohistochemistry, and real-time polymerase chain reaction.

Results: The administration of ALS-L1023 resulted in a weight reduction without changes in food intake. It also markedly inhibited hyperglycemia and hypoinsulinemia, and restored β-cell mass that was severely impaired in OLETF rats. There was a decrease in lipid accumulation in the liver and skeletal muscle of the obese rats after treatment with ALS-L1023. Concomitantly, there was an increase in the expression levels of fatty acid-oxidizing enzymes (AMPKα2, ACOX, MCAD, and VLCAD) in the liver and skeletal muscle after ALS-L1023 treatment. Furthermore, ALS-L1023 attenuated the pancreatic inflammation including the infiltration of CD68-positive macrophages and mast cells, in addition to attenuating the expression of inflammatory factors (IL-6 and CD68).

Conclusions: These results suggest that treatment with ALS-L1023 may reduce weight gain, elevated glucose levels, and β-cell loss, by changing the expression of fatty acid-oxidizing enzymes in the liver and skeletal muscle, including inflammatory factors in the pancreas. These findings indicate that ALS-L1023 may be an effective therapeutic strategy to treat human obesity and type 2 diabetes.

Keywords: Diabetes; Ectopic lipid; Lemon balm; Melissa officinalis; OLETF rat; Obesity; Pancreatic inflammation.

MeSH terms

  • Animals
  • Blood Glucose / drug effects*
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2
  • Diet, High-Fat / adverse effects
  • Dose-Response Relationship, Drug
  • Insulin-Secreting Cells / drug effects*
  • Insulin-Secreting Cells / metabolism
  • Lipid Metabolism / drug effects
  • Lipid Metabolism / physiology
  • Melissa*
  • Obesity / drug therapy*
  • Obesity / etiology
  • Obesity / metabolism
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use*
  • Rats
  • Rats, Inbred OLETF
  • Rats, Long-Evans
  • Weight Gain / drug effects*
  • Weight Gain / physiology


  • ALS-L1023
  • Blood Glucose
  • Plant Extracts