Sung Min Ahn1, Ha Neui Kim2, Yu Ri Kim3, Young Whan Choi4, Cheol Min Kim5, Hwa Kyoung Shin6, Byung Tae Choi7. 1. Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan 50612, Republic of Korea; Research Center for Anti-aging Technology Development, Pusan National University, Busan 46241, Republic of Korea. 2. Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan 50612, Republic of Korea; Korean Medical Science Research Center for Healthy-Aging, Pusan National University, Yangsan 50612, Republic of Korea. 3. Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan 50612, Republic of Korea. 4. Research Center for Anti-aging Technology Development, Pusan National University, Busan 46241, Republic of Korea; Department of Horticultural Bioscience, College of Natural Resource and Life Science, Pusan National University, Miryang 50463, Republic of Korea. 5. Research Center for Anti-aging Technology Development, Pusan National University, Busan 46241, Republic of Korea; Department of Biochemistry, College of Medicine, Pusan National University, Yangsan 50612, Republic of Korea. 6. Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan 50612, Republic of Korea; Research Center for Anti-aging Technology Development, Pusan National University, Busan 46241, Republic of Korea; Korean Medical Science Research Center for Healthy-Aging, 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. 7. Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan 50612, Republic of Korea; Research Center for Anti-aging Technology Development, Pusan National University, Busan 46241, Republic of Korea; Korean Medical Science Research Center for Healthy-Aging, 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: Polygonum multiflorum Thunb. has been used widely in East Asia in treatment of diseases associated with aging. Emodin, an active component from Polygonum multiflorum Thunb., provides benefits for brain disturbances induced by severe cerebral injury. AIM OF THE STUDY: We investigated the neuroprotective effect of emodin from Polygonum multiflorum Thunb. against glutamate-induced oxidative toxicity and cerebral ischemia. MATERIALS AND METHODS: For examination of neuroprotective effects of emodin, cell viability, cytotoxicity, flow cytometry, and Western blot were performed in HT22 cells and infarct volume, behavioral tests and Western blot in a mouse model of photothrombotic ischemic stroke. RESULTS: Pretreatment with emodin resulted in significantly reduced glutamate-induced apoptotic cell death in HT22 cells. However, blocking of phosphatidylinositol-3 kinase (PI3K) activity with LY294002 resulted in significantly inhibited cell survival by emodin. Exposure of glutamate-treated cells to emodin induced an increase in the level of Bcl-2 expression, whereas the expression of Bax and active caspase-3 proteins was significantly reduced. In addition, treatment with emodin resulted in increased phosphorylation of Akt and cAMP response element binding protein (CREB), and expression of mature brain-derived neurotrophic factor (BDNF). This expression by emodin was also significantly inhibited by blocking of PI3K activity. In a photothrombotic ischemic stroke model, treatment with emodin resulted in significantly reduced infarct volume and improved motor function. We confirmed the critical role of the expression levels of Bcl-2/Bax, active caspase-3, phosphorylated (p)Akt, p-CREB, and mature BDNF for potent neuroprotective effects of emodin in cerebral ischemia. CONCLUSIONS: These results suggest that emodin may afford a significant neuroprotective effect against glutamate-induced apoptosis through activation of the PI3K/Akt signaling pathway, and subsequently enhance behavioral function in cerebral ischemia.
ETHNOPHARMACOLOGICAL RELEVANCE: Polygonum multiflorum Thunb. has been used widely in East Asia in treatment of diseases associated with aging. Emodin, an active component from Polygonum multiflorum Thunb., provides benefits for brain disturbances induced by severe cerebral injury. AIM OF THE STUDY: We investigated the neuroprotective effect of emodin from Polygonum multiflorum Thunb. against glutamate-induced oxidative toxicity and cerebral ischemia. MATERIALS AND METHODS: For examination of neuroprotective effects of emodin, cell viability, cytotoxicity, flow cytometry, and Western blot were performed in HT22 cells and infarct volume, behavioral tests and Western blot in a mouse model of photothrombotic ischemic stroke. RESULTS: Pretreatment with emodin resulted in significantly reduced glutamate-induced apoptotic cell death in HT22 cells. However, blocking of phosphatidylinositol-3 kinase (PI3K) activity with LY294002 resulted in significantly inhibited cell survival by emodin. Exposure of glutamate-treated cells to emodin induced an increase in the level of Bcl-2 expression, whereas the expression of Bax and active caspase-3 proteins was significantly reduced. In addition, treatment with emodin resulted in increased phosphorylation of Akt and cAMP response element binding protein (CREB), and expression of mature brain-derived neurotrophic factor (BDNF). This expression by emodin was also significantly inhibited by blocking of PI3K activity. In a photothrombotic ischemic stroke model, treatment with emodin resulted in significantly reduced infarct volume and improved motor function. We confirmed the critical role of the expression levels of Bcl-2/Bax, active caspase-3, phosphorylated (p)Akt, p-CREB, and mature BDNF for potent neuroprotective effects of emodin in cerebral ischemia. CONCLUSIONS: These results suggest that emodin may afford a significant neuroprotective effect against glutamate-induced apoptosis through activation of the PI3K/Akt signaling pathway, and subsequently enhance behavioral function in cerebral ischemia.