Characterization of Anti-neurodegenerative Effects of Polygala tenuifolia in A.BETA.(25-35)-Treated Cortical Neurons

Abstract

The root of Polygala tenuifolia WILLD (PT) (Japanese name: Onji) is a well-known traditional Chinese medicine used as an expectorant, a tonic, a tranquillizer and an anti-dementia drug. However, basic researches of the anti-dementia effects are very few in spite of PT being generally recognized as a good herbal drug for amnesia. It was reported that 80% ethanol extract of PT and the methanol extract of PT reverse scopolamine-induced cognitive impairments in rats. 1,2) Acetylcholinestrase (AChE) activity is inhibited in vitro by 80% ethanol extract of PT.1,3) Onjisaponin F, a constituent in PT, increases cholineacetyltransferase (ChAT) mRNA level in rat basal forebrain cell, and. Taken together, transient enhancement of cholinergic systems by PT may be involved in the memory improvement seen in like the scopolamine model. However, practical dementia is caused by irreversible neuronal damage involving neuronal death, neuritic atrophy and synaptic loss. Especially in case of Alzheimer's disease, neuritic atrophy and synapse loss are earlier events than neuronal death are, and are critical for memory disorder. [4][5][6][7][8] Previous our studies suggested that compounds which showed synaptic regeneration activity in cultured neurons were also active for memory impairment in vivo using Alzheimer's disease model mice.9-11) Although protective effects of PT on neuronal death were shown in amyloid b (Ab), glutamate or NMDA-induced neuronal damage, effects of PT on atrophy of neuritis and synaptic loss never have been investigated yet.1,12) Therefore, we aimed in this study to characterize activities of PT under Ab-induced neuritic damage. MATERIALS AND METHODS MaterialsThirty gram of roots of Polygala tenuifolia WILLD (PT) was extracted with 600 ml of water at 100°C for 40 min. This crude drug was purchased from Tochimoto Tenkaido (Osaka, Japan). The decoction was evaporated under reduced pressure and freeze-dried of extract powder (yield: 8.02 g). The extract was then dissolved in sterilized distilled water at 1000 times concentrations of final concentrations. Ab (25-35) (Sigma, Saint Louis, MO, U.S.A.) was dissolved in sterile distilled water at a concentration of 5 mM, and was incubated at 37°C for 3 d to allow fibril formation. [Gly 14 ]-Humanin was purchased from Phoenix Pharmaceuticals (Belmont, CA, U.S.A.) as a positive control for neuronal protection. A monoclonal antibody to phosphorylated neurofilament-H (NF-H) was purchased from Sternberger Monoclonals (Lutherville, MD, U.S.A.). A monoclonal antibody to microtubule-associated protein 2 (MAP2), an antiserum to MAP2, polyclonal antibody to MAP2 and a monoclonal antibody to synaptophysin were purchased from Chemicon (Temecula, CA, U.S.A.). Alexa Fluor 488-conjugated goat anti-mouse IgG and Alexa Fluor 546-conjugated goat antirabbit IgG were purchased from Molecular Probes (Eugene, OR, U.S.A.). Aqua Poly Mont was purchased from Polyscience (Warrington, PA, U.S.A.).Primary Culture Embryos were removed from pregnant Sprague Dawley rats (Japan SLC, Shizuoka, J...

Polygalasaponin XXXII, a triterpenoid saponin from Polygalae Radix, attenuates scopolamine-induced cognitive impairments in mice

“…We discovered that P3 protected primary cortical neurons against serum deficiency and glutamate-induced damage and PC12 cells against H 2 O 2 -induced death. Several researchers have demonstrated that Polygalae Radix extract provides neuroprotection of PC12 cells against 6-hydroxydopamine (6-OHDA)-induced damage and of primary cortical neurons against Aβ 25-35 -induced cell damage [24,25] . These results suggest that P3 may be effective in the treatment of various neurodegenerative diseases.…”

An LC‐MS/MS method for determination of 3,6′‐disinapoylsucrose in rat plasma and its application to a pharmacokinetic study

“…Yuan-Zhi has been used as a main ingredient in a TCM formula 'Kaixinsan' , which has shown clinical benefits for the treatment of insomnia, palpitations with anxiety, restlessness and disorientation (Howes and Houghton, 2003;Wang et al, 2007). Previous studies have demonstrated that Yuan-Zhi water extract has significant effects for neuroprotection in cultured cell model (Naito and Tohda, 2006) and improving learning memory of mice (Egashira et al, 2003). Yuan-Zhi ethanol extract is capable of reversing scopolamine-induced cognitive impairment by inhibiting acetylcholinesterase activity (Park et al, 2002;Ikeya et al, 2004), and improves stress-induced memory impairments through increment of glucose utilization and total neural cell adhesion molecule levels in rat brains (Shin et al, 2009).…”

Polygalasaponin XXXII from Polygala tenuifolia root improves hippocampal-dependent learning and memory

“…More recently, there has been renewed interest in the cognition-enhancing potential of P tenuifolia root extracts. Several studies have shown that P tenuifolia extracts have cognition improving effects in vivo, in addition to protective effects on neurotoxicity that is induced in vitro by factors such as glutamate, beta-amyloid, and the C-terminal fragment of amyloid precursor protein (CT) [2,[4][5][6] . However, the biologically active components from these extracts still require identification, and their in vivo functions and mechanisms must be understood before P tenuifolia root extracts can be developed into therapeutic drugs.…”