Synergistic and antagonistic interactions of anticholinesterase terpenoids in Salvia lavandulaefolia essential oil

Pharmacol Biochem Behav. 2003 Jun;75(3):661-8. doi: 10.1016/s0091-3057(03)00125-4.


In vitro anticholinesterase activities of eight commercially available terpenoid constituents of Salvia lavandulaefolia have been investigated. These included 1,8-cineole, camphor, alpha-pinene, beta-pinene, borneol, caryophyllene oxide, linalool and bornyl acetate. Dose-dependent inhibition of acetylcholinesterase (AChE) by these chemical constituents was determined using the method of Ellman [Biochem. Pharmacol. 7 (1961) 88]. The IC50 value of 1,8-cineole was 0.06+/-0.01 mg/ml similar to that of the essential oil (0.05+/-0.01 mg/ml). Analyses of the expected inhibitions based on the prediction of a zero interactive response of a combination at its naturally occurring ratios were carried out in comparison with observed inhibition. Minor synergy was apparent in 1,8-cineole/alpha-pinene and 1,8-cineole/caryophyllene oxide combinations, with interaction indexes not exceeding 0.5. In contrast, a combination of camphor and 1,8-cineole was antagonistic with an interaction index of 2. A combination of all eight compounds was zero interactive. A combination of six constituents, excluding 1,8-cineole and camphor, was used to compare the method of expected response of a combination with a method of summation. These findings reveal that the inhibitory activity of the oil results from a complex interaction between its constituents, which produce both synergistic and antagonistic responses between the component terpenes. Understanding such interactions is important in comparing species on the basis of chemical composition.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cholinesterase Inhibitors / chemistry
  • Cholinesterase Inhibitors / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Drug Synergism
  • Oils, Volatile / chemistry
  • Oils, Volatile / pharmacology*
  • Plant Leaves
  • Salvia*
  • Terpenes / chemistry
  • Terpenes / pharmacology*


  • Cholinesterase Inhibitors
  • Oils, Volatile
  • Terpenes