Sun Haeng Park1, Seol Jang2, Si Woo Lee3, Sun Dong Park4, Yoon-Young Sung2, Ho Kyoung Kim5. 1. Herbal Medicine Research, Korea Institute of Oriental Medicine (KIOM), 1672 Yuseong-daero, Yuseong-gu, Daejeon 305-811, Republic of Korea; Department of Korean Medicine, Dongguk University, 32 Donggukro, Ilsandonggu, Goyangsi, Kyeonggido 10326, South Korea. 2. Herbal Medicine Research, Korea Institute of Oriental Medicine (KIOM), 1672 Yuseong-daero, Yuseong-gu, Daejeon 305-811, Republic of Korea. 3. Future Medicine Division, Korea Institute of Oriental Medicine (KIOM), 1672 Yuseong-daero, Yuseong-gu, Daejeon 305-811, Republic of Korea. 4. Department of Korean Medicine, Dongguk University, 32 Donggukro, Ilsandonggu, Goyangsi, Kyeonggido 10326, South Korea. 5. Herbal Medicine Research, Korea Institute of Oriental Medicine (KIOM), 1672 Yuseong-daero, Yuseong-gu, Daejeon 305-811, Republic of Korea. Electronic address: hkkim@kiom.re.kr.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Akebia quinata Decaisne extract (AQE; Lardizabalaceae) is used in traditional herbal medicine for stress- and fatigue-related depression, improvement of fatigue, and mental relaxation. AIM OF THE STUDY: To clarify the effects of AQE on stress-induced fatigue, we investigated the neuroprotective pharmacological effects of A. quinata Decaisne in mice exposed to chronic restraint stress. MATERIALS AND METHODS: Seven-week old C57BL/6 mice chronically stressed by immobilization for 3 h daily for 15 d and non-stressed control mice underwent daily oral administration of AQE or distilled water. The open field, sucrose preference, and forced swimming behavioral tests were carried out once weekly, and immunohistochemical analyses of NeuN, brain-derived neurotrophic factor (BDNF), phosphorylated cAMP response element-binding (CREB) protein, and BDNF receptor tropomyosin receptor kinase B (TrkB) in striatum and hippocampus were performed at the end of the experimental period. Brain levels of serotonin, adrenaline, and noradrenaline as well as serum levels of corticosterone were measured. RESULTS: Behavioral tests showed that treatment with AQE improved all lethargic behaviors examined. AQE significantly attenuated the elevated levels of adrenaline, noradrenaline, and serotonin in the brain and corticosterone, alanine transaminase, and aspartate transaminase levels in the serum. Histopathological analysis showed that AQE reduced liver injury and lateral ventricle size in restraint-stress mice via inhibition of neuronal cell death. Immunohistochemical analysis showed increased phosphorylation of CREB and expression of BDNF and its receptor TrkB in striatum and hippocampus. Chlorogenic acid, isochlorogenic acid A, and isochlorogenic acid C were identified as the primary components of AQE. All three agents increased expression of BDNF in SH-SY5Y cells and PC12 cells with H2O2-induced neuronal cell damage. CONCLUSIONS: AQE may have a neuroprotective effect and ameliorate the effects of stress and fatigue-associated brain damage through mechanisms involving regulation of BDNF-TrkB signaling.
ETHNOPHARMACOLOGICAL RELEVANCE: Akebia quinata Decaisne extract (AQE; Lardizabalaceae) is used in traditional herbal medicine for stress- and fatigue-related depression, improvement of fatigue, and mental relaxation. AIM OF THE STUDY: To clarify the effects of AQE on stress-induced fatigue, we investigated the neuroprotective pharmacological effects of A. quinata Decaisne in mice exposed to chronic restraint stress. MATERIALS AND METHODS: Seven-week old C57BL/6 mice chronically stressed by immobilization for 3 h daily for 15 d and non-stressed control mice underwent daily oral administration of AQE or distilled water. The open field, sucrose preference, and forced swimming behavioral tests were carried out once weekly, and immunohistochemical analyses of NeuN, brain-derived neurotrophic factor (BDNF), phosphorylated cAMP response element-binding (CREB) protein, and BDNF receptor tropomyosin receptor kinase B (TrkB) in striatum and hippocampus were performed at the end of the experimental period. Brain levels of serotonin, adrenaline, and noradrenaline as well as serum levels of corticosterone were measured. RESULTS: Behavioral tests showed that treatment with AQE improved all lethargic behaviors examined. AQE significantly attenuated the elevated levels of adrenaline, noradrenaline, and serotonin in the brain and corticosterone, alanine transaminase, and aspartate transaminase levels in the serum. Histopathological analysis showed that AQE reduced liver injury and lateral ventricle size in restraint-stress mice via inhibition of neuronal cell death. Immunohistochemical analysis showed increased phosphorylation of CREB and expression of BDNF and its receptor TrkB in striatum and hippocampus. Chlorogenic acid, isochlorogenic acid A, and isochlorogenic acid C were identified as the primary components of AQE. All three agents increased expression of BDNF in SH-SY5Y cells and PC12 cells with H2O2-induced neuronal cell damage. CONCLUSIONS:AQE may have a neuroprotective effect and ameliorate the effects of stress and fatigue-associated brain damage through mechanisms involving regulation of BDNF-TrkB signaling.