Isolation of a Unique Monoterpene Diperoxy Dimer From Ziziphora clinopodioides subsp. bungeana Together With Triterpenes With Antidiabetic Properties.

INTRODUCTION

Ziziphora clinopodioides subsp. bungeana (Juz.) Rech.f. is used in traditional medicine for various purposes. Previous phytochemical studies focused on phenolic compounds, but triterpenoids were almost overlooked.

OBJECTIVE

The study focused on the isolation of compounds with dual antidiabetic activity from the aerial parts of Z. clinopodioides subsp. bungeana.

MATERIALS AND METHODS

Separation of CHCl-soluble fraction by silica gel column chromatography using different mobile phases and purification of compounds by semi-preparative HPLC or preparative TLC. The structures of pure compounds were elucidated by 1D and 2D NMR experiments along with HRMS. Compound 1 was additionally identified by the single crystal X-ray diffraction method. α-Glucosidase inhibitory assay and GLUT4 expression and translocation in C2C12 myotubes were conducted to evaluate antidiabetic potential of isolated compounds.

RESULTS

This phytochemical study led to the isolation of 20 compounds, including a unique monoterpene diperoxy dimer (1). Compounds 7 and 9-11 displayed more potent α-glucosidase inhibitory activity (IC 45.3-135.3 μM) than acarbose used as a positive control (IC 264.7 μM), while only pomolic acid (5) increased GLUT4 translocation in C2C12 myotubes in a significant manner.

CONCLUSION

Extensive chromatographic separation led to the isolation and identification of a unique monoterpene diperoxy dimer (1) from aerial parts of Z. clinopodioides subsp. bungeana. Some triterpenes inhibited α-glucosidase, another increased GLUT4 translocation. Although none of the isolated compounds demonstrated dual antidiabetic activity, selected triterpenes proved to be potent antidiabetic agents in vitro.