Ursolic acid lactone from leaves of Eucalyptus tereticornis regulates lipid accumulation and glucose uptake in cellular models

Obesity is a risk factor associated with insulin resistance and it is linked with cardiovascular disease and type 2 diabetes mellitus. The potential of natural products for treating obesity is under exploration and interest has increased in the development of treatments from natural sources with fewer adverse effects. Ursolic acid lactone (UAL) is a triterpene found in leaves of Eucalyptus tereticornis (Eu)[1] [2]. Triterpenes constitute a large family of plant natural molecules with diverse structures and functions and have been found to manifest hypolipidemic, anti-obesity and antidiabetic activity[3]. The purpose of our study is to analyze if UAL have similar properties. A crude methanolic extract (OBE100) from leaves of Eu was partitioned with ethyl acetate, concentrated and purified by Sephadex LH-20. UAL was purified by Sephadex column and preparative chromatography from OBE100. Murine 3T3-L1 adipocyte and C2C12 myocyte cell lines were used to evaluate UAL effects. We determined treatments concentrations after the analysis of cytotoxicity levels of the molecule. We found UAL reduced 32% adipocyte lipid content after 7 days of treatment compared to 18% reduction by metformin treatment. This effect was accompanied by inhibition of leptin production. We also found that this triterpene stimulated up to 24% glucose uptake in muscle cells. To the best of our knowledge, it is the first time that UAL has been proven to exhibit anti-lipogenesis effect in adipocyte cells and stimulation glucose uptake in myocyte cells suggesting its potential future application as antiobesity and antidiabetic agent.

• References

• 1 Maurya A, Srivastava SK. Determination of ursolic acid and ursolic acid lactone in the leaves of eucalyptus tereticornis by hplc. J Braz Chem Soc 2012; 23 (03) : 468-472
• 2 Ceballos S, En A Guilí, Lorena D, Noz M, Castã A, Echeverri LF, Acín S, Bal N, Bal Azar N. Immunometabolic regulation by triterpenes of Eucalyptus tereticornis in adipose tissue cell line models. Phytomedicine 2018; 15 (50) : 109-117
• 3 Sharma H, Kumar P, Deshmukh RR, Bishayee A, Kumar S. Pentacyclic triterpenes: New tools to fight metabolic syndrome. Phytomedicine 2018; 50: 166-177.