Abietane diterpenoids as butyrylcholinesterase inhibitors from Salvia species

Abstract

Salvia (sage) species have been used as medicinal plants since ancient times in the treatment of cold, sore throat, tuberculosis, angina pectoris, stomache ache, and menstrual disorders and they have been known as sedative, anti-depressant and memory enhancer agents since antiquity. In Europe, sage plants (namely S. officinalis, S. lavandulifolia, S. fruticosa) have traditional reputations that justify investigation for a potential role in reducing cognitive decline in the elderly. Salvia species (Lamiaceae family) are rich in abietane diterpenes and flavonoids and other phenolics which have antioxidant, antibacterial, antiviral, cytotoxic and antitumor properties. In this presentation, the anticholinesterase activity results of 50 abietane diterpenoids will be given which were isolated from a number of Anatolian Salvia species.They were investigated at 200µM concentration against AChE and BChE enzymes by the Ellman method in vitro. The diterpenoids exhibited about 50% inhibition at least against one of the two cholinesterase enzymes, they were then subjected for the same test at the five different doses (12.5, 25, 50,100 and 200µM) to find their IC50 values. Interestingly, most of them exhibited more or less activity against butyryl cholinesterase (BChE) enzyme, and among them, bractealine, 6-hydroxysalvinolone, royleanone 12-methyl ether, ferruginol and taxodione showed high activity with the IC50 values of 3.43, 17.21, 56.48, 17,49 and 7.73µM, respectively, while their inhibition on AChE was found to be fairly weak. Hence, it was not observed a real correlation between the results against the two enzymes. Rationalization of the differences in the enzyme active sites has been performed using docking studies. Thus, abietane diterpenoids were found to be potent BChE inhibitors which might verify the ethnobotanical uses of Salvia extracts as memory enhancers.