Anti-Oxidant Activity of Gallotannin-Enriched Extract of Galla Rhois Can Associate with the Protection of the Cognitive Impairment through the Regulation of BDNF Signaling Pathway and Neuronal Cell Function in the Scopolamine-Treated ICR Mice.

Park Park,Kang Kang,Jung Jung,Hong Hong,Hwang Hwang,Bae Bae,Choi Choi,Kim Kim

doi:10.3390/antiox8100450

Park Park, Kang Kang + Show 6 more

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https://doi.org/10.3390/antiox8100450

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Abstract

The antibacterial, anti-inflammatory, anti-metastatic/anti-invasion activities and laxative activity of Galla Rhois (GR) are well-known, although the neuropreservation effects of their extracts are still to be elucidated. To investigate the novel therapeutic effects and molecular mechanism of GR on alleviation of cognitive impairment, two different dosages of gallotannin-enriched GR (GEGR) were administered to Korl:ICR mice for three weeks, and to induce memory impairment, scopolamine (SP) was administered during the last seven days of the GEGR treatment period. GEGR showed the high level of the free radical scavenging activity to DPPH and suppressive activity to reactive oxygen species (ROS) in B35 cells as well as enhanced SOD and CAT activity in brains of the SP-induced model. Latency time for memory impairment assessed by the passive avoidance test significantly protected in the SP+GEGR treated group as compared to the SP+Vehicle treated group. Moreover, similar protective effects were observed on the secretion of BDNF in SP+GEGR treated mice. The expression of TrkB receptor, and phosphorylation of PI3K on the TrkB receptor signaling pathway were dramatically protected in the SP-induced model after GEGR treatment, whereas the expression of p75NTR receptor, the phosphorylation of JNK, and expression of Bax/Bcl-2 on the p75NTR receptor signaling pathway was significantly protected in the same group. Furthermore, the GEGR treated SP-induced model showed decreased number of dead neural cells and suppressed acetylcholine esterase (AChE) activity and inhibited inflammatory responses. Taken together, these results indicate that the anti-oxidant activity of GEGR contributes to improving the neuronal cell function and survival during cognitive impairment in the SP-induced model through regulation of BDNF secretion and their receptor signaling pathway.

Highlights

Oxidative stress leading to DNA oxidation, protein oxidation, lipid oxidation, and glycoxidation induces an imbalance between the production of reactive oxygen species (ROS) and the antioxidantAntioxidants 2019, 8, 450; doi:10.3390/antiox8100450 www.mdpi.com/journal/antioxidantsAntioxidants 2019, 8, 450 defense system [1]
The present study evaluated the possibility of developing a new natural medicine by investigating cognitive impairment, cell function and survival, and brain-derived neurotrophic factor (BDNF) regulation during the neuroprotective effects of gallotannin-enriched Galla Rhois (GEGR) in an SP-induced Alzheimer’s disease (AD) model
A similar anti-oxidant activity of GEGR was observed in the inhibitory effects against H2 O2 -induced ROS production, wherein the ROS production was remarkably decreased in GEGR+H2 O2 treated B35 cells without any significant changes in their morphology (Figure 1B)

Summary

Introduction

Oxidative stress leading to DNA oxidation, protein oxidation, lipid oxidation, and glycoxidation induces an imbalance between the production of reactive oxygen species (ROS) and the antioxidantAntioxidants 2019, 8, 450; doi:10.3390/antiox8100450 www.mdpi.com/journal/antioxidantsAntioxidants 2019, 8, 450 defense system [1]. Oxidative stress leading to DNA oxidation, protein oxidation, lipid oxidation, and glycoxidation induces an imbalance between the production of reactive oxygen species (ROS) and the antioxidant. Aβ accumulation results in increased oxidative stress and mitochondrial dysfunction via inhibition of ATP production and increase of reactive oxygen species (ROS) generation [3,4,5]. The aggregation and production of Aβ are significantly inhibited by exposure to gallotannin and tannic acid in in vitro studies and the PSAPP mouse model presenting AD-like pathology [7,8]. The inhibitory effects of tannic acid have been verified during the in vitro aggregation analysis of tau peptide R3 and electron microscopy study of human full-length tau protein (tau441) [12,13]. The neuroprotective effects and the molecular mechanism of gallotannin-enriched Galla Rhois (GEGR) in the scopolamine (SP)-induced memory impairment model are not fully investigated, gallotannin, gallic acid, and methyl gallate are identified as the major components of GEGR [14]

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