Sun Young Lee1, Sung Min Ahn1, Ziyu Wang2, Young Whan Choi2, Hwa Kyoung Shin3, Byung Tae Choi4. 1. Korean Medical Science Research Center for Healthy-Aging, Pusan National University, Yangsan 50612, Republic of Korea. 2. Department of Horticultural Bioscience, College of Natural Resource and Life Science, Pusan National University, Miryang 50463, Republic of Korea. 3. Korean Medical Science Research Center for Healthy-Aging, Pusan National University, Yangsan 50612, Republic of Korea; Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan 50612, Republic of Korea; Division of Meridian and Structural Medicine, School of Korean Medicine, Pusan National University, Yangsan 50612, Republic of Korea. 4. Korean Medical Science Research Center for Healthy-Aging, Pusan National University, Yangsan 50612, Republic of Korea; Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan 50612, Republic of Korea; Division of Meridian and Structural Medicine, School of Korean Medicine, Pusan National University, Yangsan 50612, Republic of Korea. Electronic address: choibt@pusan.ac.kr.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Since ancient times, Polygonum multiflorum Thunb. has been used to treat premature grey hair, dizziness, and blurred vision in East Asia. A major bioactive constituent of this medicinal herb, 2,3,5,4'-tetrahydoxystilbene-2-O-β-D-glucoside (THSG), has antioxidant activity and exerts beneficial effects on cognition and memory. AIM OF THE STUDY: The purpose of the current study was to determine if THSG affects hippocampal neuronal cell death and mitochondrial function following exposure to oxidative stress. MATERIALS AND METHODS: HT22 hippocampal cells with or without THSG pretreatment were exposed to glutamate, and the effects on cell viability and expression of molecules related to apoptotic cell death were examined using biochemical techniques, flow cytometry, western immunoblotting, and real-time polymerase chain reaction. RESULTS: Pretreatment with THSG significantly attenuated glutamate-induced loss of cell viability and release of lactate dehydrogenase as well as apoptotic cell death. THSG inhibited generation of reactive oxygen species (ROS), expression of heme oxygenase-1, and activation of caspase-3 and calpain-1 proteases, all of which were increased by glutamate. THSG inhibited glutamate-induced disruption of mitochondrial membrane potential (MMP) and voltage-dependent anion channel-1. It also regulated the ratio of Bax to Bcl-2. CONCLUSIONS: These results indicate that THSG has a marked neuroprotective effect against glutamate-induced hippocampal damage by decreasing ROS production and stabilizing MMP. These findings suggest the potential of THSG as a new therapeutic agent for the treatment of cognitive disorders.
ETHNOPHARMACOLOGICAL RELEVANCE: Since ancient times, Polygonum multiflorum Thunb. has been used to treat premature grey hair, dizziness, and blurred vision in East Asia. A major bioactive constituent of this medicinal herb, 2,3,5,4'-tetrahydoxystilbene-2-O-β-D-glucoside (THSG), has antioxidant activity and exerts beneficial effects on cognition and memory. AIM OF THE STUDY: The purpose of the current study was to determine if THSG affects hippocampal neuronal cell death and mitochondrial function following exposure to oxidative stress. MATERIALS AND METHODS: HT22 hippocampal cells with or without THSG pretreatment were exposed to glutamate, and the effects on cell viability and expression of molecules related to apoptotic cell death were examined using biochemical techniques, flow cytometry, western immunoblotting, and real-time polymerase chain reaction. RESULTS: Pretreatment with THSG significantly attenuated glutamate-induced loss of cell viability and release of lactate dehydrogenase as well as apoptotic cell death. THSG inhibited generation of reactive oxygen species (ROS), expression of heme oxygenase-1, and activation of caspase-3 and calpain-1 proteases, all of which were increased by glutamate. THSG inhibited glutamate-induced disruption of mitochondrial membrane potential (MMP) and voltage-dependent anion channel-1. It also regulated the ratio of Bax to Bcl-2. CONCLUSIONS: These results indicate that THSG has a marked neuroprotective effect against glutamate-induced hippocampal damage by decreasing ROS production and stabilizing MMP. These findings suggest the potential of THSG as a new therapeutic agent for the treatment of cognitive disorders.