Potential neuroprotective agent from botanical extract: An experience of using Verbena officinalis against β-amyloid peptide neurotoxicity

Abstract

Increasing lines of evidence have demonstrated the potential of using botanical extract to prevent neurodegenerative diseases. Verbena officinalis Linn. (Verbenaceae) is a perennial plant which has been used as herbal medicine or health supplement in both Western and Eastern countries for centuries. It has been used to treat acute dysentery, enteritis, amenorrhea and depression. In addition, aqueous extract of V. officinalis has been shown to exhibit sedative effects in an animal model. Since it has a wide array of biological effects, we hypothesized that V. officinalis can exert cytoprotective effects in central nervous system. Lactate dehydrogenase (LDH) assay was used as index of cytotoxicity for various toxins/stresses. Prior to the exposure of -amyloid (A ) peptide and reducing agent dithiothreitol, treatment of aqueous extracts of V. officinalis significantly attenuated their toxicity determined by LDH assay. As extracellular accumulation of A peptide has been considered to be an important pathological factor in Alz heimer’s disease (AD), we have further explored the neuroprotection of V. officinalis aqueous extracts against A . Treatment of V. officinalis aqueous extracts attenuated A -triggered DEVDand VDVAD-cleavage activities in dose-dependent manner. Furthermore, V. officinalis attenuated A -triggered apoptosis conDownlofirmed by DAPI staining. According to our previous findings, A peptide can activate the stress kinases, including double-stranded RNA-dependent protein kinase (PKR) and c-Jun N-terminal kinase (JNK). Our present results showed that V. officinalis attenuated the phosphorylation of both PKR and JNK in A -treated neurons by Western blot analysis. Taken together, we have proved our hypothesis by showing the novel neuroprotective effects of V. officinalis. As V. officinalis has long been used for many years to be a folk medicine, our study may provide a potential lead as a neuroprotective agent against neuronal loss in AD. Acknowledgement: S.W.L. and M.S.Y. are supported by postgraduate studentship from The University of Hong Kong. The study is partially supported by HKU Seed Funding for Basic Research (2004 & 2005) and HKU University Strategic Theme Research on Healthy Aging to R.C.C.C.