Unusual norcucurbitacin glycosides from the roots of Siraitia grosvenorii

Abstract

Siraitia grosvenorii Swingle is one of the first approved medicine food homology species in China, and it has been used as a natural sweetener in the food industry and as a traditional medicine to relieve cough and reduce phlegm. However, many S. grosvenorii roots are discarded yearly, which results in a great waste of resources. Twelve undescribed norcucurbitacin-type triterpenoid glycosides, siraitiaosides A-L (1-12), and six known analogs (13-18) were isolated from the roots of S. grosvenorii. The structures of isolated norcucurbitacin glycosides were elucidated by comprehensive data analyses, including HRESIMS, UV, IR, NMR, ECD calculations, and X-ray crystallography analysis. Siraitiaosides A-E (1-5) featured an unusual 19,29-norcucurbitacin framework while siraitiaosides F-L (6-12) featured a rare 29-norcucurbitacin framework. Notably, compound 4 displayed moderate anti-acetylcholinesterase (AChE) activity with an IC50 of 21.0 μM, meanwhile, compounds 16 and 18 exhibited pronounced cytotoxic activities against MCF-7, CNE-1, and HeLa cancer cell lines with IC50 values of 2.1-15.2 μM. In silico studies showed that compound 4 bound closely to AChE with a binding energy of -5.04 kcal/mol, and compound 18 could tightly bind to PI3K, AKT1, ERK2, and MMP9 proteins that related to autophagy, apoptosis, migration/invasion, and growth/proliferation. In summary, the roots of Siraitia grosvenorii have potential medicinal values due to the multiple bioactive components.