Inhibitory effect of Turkish Rosmarinus officinalis L. on acetylcholinesterase and butyrylcholinesterase enzymes
Introduction
The most common form of dementia is known as Alzheimer’s disease (AD), which is the loss of intellectual and social abilities severe enough to interfere with daily functioning (Cummings, 2004, Mattson, 2004). Although symptoms can vary widely, the first problem many people notice is forgetfulness severe enough to affect their work, lifelong hobbies or social life (Verghese et al., 2003). Inhibition of acetylcholinesterase (AChE), the key enzyme in the breakdown of acetylcholine, is considered one of the treatment strategies against several neurological disorders such as AD, senile dementia, ataxia, and myasthenia gravis (Mukherjee et al., 2007, Orhan et al., 2006). Within the past few years, some synthetic compounds (tacrine, rivastigmine, donepezil, and galanthamine) have become available for clinical use; however, none of them have ability to stop the disease. Therefore, there is still a great demand in order to find new drug candidates for AD treatment.
On the other hand, Rosmarinus officinalis L. (Lamiaceae), also known as rosemary, is an aromatic evergreen shrub widely distributed throughout the Mediterranean region. R. officinalis L. has a very old reputation for improving memory and has been used as a symbol of remembrance in Europe (Moss, Cook, Wesnes, & Duckett, 2003).
As part of our continuing studies into discovery of new cholinesterase inhibitors from Turkish medicinal plants and pure compounds (Orhan et al., 2007, Orhan et al., 2004, Orhan et al., in press), we have now focused on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory effects of Turkish rosemary, R. officinalis L. (RO). For this intention, we have tested in vitro anticholinesterase action of the essential oil and petroleum ether (RO–PE), chloroform (RO–CHCl3), ethyl acetate (RO–EtOAc), and methanol (RO–MeOH) extracts obtained from RO by the spectrophotometric method of Ellman using ELISA microplate-reader at 0.2, 0.5, and 1.0 mg/mL concentrations. Furthermore, rosmarinic acid quantification was performed in RO–MeOH using reversed phase-HPLC and tested for its AChE and BChE inhibitory activities in the same manner, while chemical composition of the essential oil was determined by capillary GC–MS.
Section snippets
Plant material
The herbs of RO were collected from the vicinity of Edremit town of Balikesir province (Turkey) in July, 2007. Voucher specimen of the plant is deposited in the Herbarium of Faculty of Pharmacy, Ankara University, Ankara, Turkey (Code no. AEF 23852).
Preparation of the extracts
The dried and powdered material of RO was weighed accurately (31.96 g) and successively extracted with petroleum ether (PE) (1 × 1 L), chloroform (CHCl3) (2 × 1 L), ethyl acetate (EtOAc) (1 × 1 L), and methanol (MeOH) (5 × 1 L). The yields of the extracts are
Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities
At 0.2, 0.5, and 1.0 mg/mL concentrations; the essential oil of RO as well as its PE, CHCl3, EtOAc, and MeOH extracts along with rosmarinic acid was tested for their AChE and BChE inhibitory activities in vitro by spectrophotometric Ellman method. As seen in Table 1, none of the extracts had an ability to inhibit AChE at 1 mg/mL, whereas only the essential oil was active against this enzyme having 63.7 ± 1.2% of inhibition. Besides, the extracts were not able to inhibit AChE and BChE at 0.2 and 0.5
Discussion
Rosemary, used also as an aromatic tea and in aromatherapy, has been examined for its influence on mood and cognition and concluded that its essential oil produced a significant enhancement of performance and overall quality of memory in healthy adults (Moss et al., 2003). Most recently, two articles have reported on AChE inhibitory activity of the essential oil of RO. Rosemary essential oil was previously found to exhibit a moderate inhibition on AChE, which is in accordance with our data (
Conclusion
In this study, we demonstrated AChE and BChE inhibitory activities of the essential oil and extracts of RO growing in Turkey, established chemical composition of the essential oil which had quite notable inhibitions towards both AChE and BChE, and determined rosmarinic acid amount in the methanolic extract of RO that showed a remarkable BChE-inhibitory effect. 1,8-Cineole and α-pinene were found as the two major monoterpenes in our rosemary oil and we conclude that anticholinesterase activity
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