Role of membranes on the antibacterial and anti-inflammatory activities of the bioactive compounds from Hypoxis rooperi corm extract

Hypoxis rooperi corm extract ('African potato') is known for its traditional and ethnomedical uses in the treatment of a large variety of diseases. Its main bioactive compound hypoxoside (HYP) and its aglycone derivative rooperol (RO) were isolated and the interaction of these compounds with several types of model membranes was studied in order to contribute to the understanding of their molecular mechanism. The results show that RO abolishes the main transition phase and perturb the van der Waals interactions between phospholipid acyl chains in a stronger way than HYP in dimiristoylphosphatidylcholine (DMPC), dielaidoylphosphatidylethanolamine (DEPE) and dimiristoylphosphatidylglycerol membranes (DMPG), probably indicating that this molecule inserts into the bilayer. This effect decreases as the acyl chain length of the phospholipid increases. RO also promoted the formation of hexagonal HII phases at lower temperatures compared to pure DEPE. On the contrary, HYP showed a shallow interaction with phospholipids. This compound promoted the formation of gel-fluid like intermediate structures with isotropic motion in phosphatidylglycerol membranes at physiological pH, and affected the phospholipid/water interface probably through the variation of the surface charge of the phospholipid phosphate groups. Moreover, RO inhibited Staphylococcus aureus in a stronger manner than Escherichia coli and promoted a higher leakage level in E. coli, PG and PE-containing synthetic membranes. Furthermore, RO showed a significant degree of inhibition of cyclooxygenase-2 (COX-2) and cyclooxygenase-1 (COX-1) evidencing an approximate COX-2/COX-1 IC50 ratio of 1.9, therefore this compound may be responsible for the anti-inflammatory activity of H. rooperi corm extract. These results may contribute to understand the molecular mechanism of the antibacterial and/or anti-inflammatory properties of the bioactive compounds deriving from the African potato corm extract.