PMID- 29630998 OWN - NLM STAT- MEDLINE DCOM- 20181016 LR - 20191210 IS - 1872-7573 (Electronic) IS - 0378-8741 (Linking) VI - 222 DP - 2018 Aug 10 TI - Akebia quinata Decaisne aqueous extract acts as a novel anti-fatigue agent in mice exposed to chronic restraint stress. PG - 270-279 LID - S0378-8741(17)33257-9 [pii] LID - 10.1016/j.jep.2018.04.010 [doi] AB - 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 H(2)O(2)-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. CI - Copyright (c) 2018. Published by Elsevier B.V. FAU - Park, Sun Haeng AU - Park SH AD - 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. FAU - Jang, Seol AU - Jang S AD - Herbal Medicine Research, Korea Institute of Oriental Medicine (KIOM), 1672 Yuseong-daero, Yuseong-gu, Daejeon 305-811, Republic of Korea. FAU - Lee, Si Woo AU - Lee SW AD - Future Medicine Division, Korea Institute of Oriental Medicine (KIOM), 1672 Yuseong-daero, Yuseong-gu, Daejeon 305-811, Republic of Korea. FAU - Park, Sun Dong AU - Park SD AD - Department of Korean Medicine, Dongguk University, 32 Donggukro, Ilsandonggu, Goyangsi, Kyeonggido 10326, South Korea. FAU - Sung, Yoon-Young AU - Sung YY AD - Herbal Medicine Research, Korea Institute of Oriental Medicine (KIOM), 1672 Yuseong-daero, Yuseong-gu, Daejeon 305-811, Republic of Korea. FAU - Kim, Ho Kyoung AU - Kim HK AD - 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. LA - eng PT - Journal Article DEP - 20180406 PL - Ireland TA - J Ethnopharmacol JT - Journal of ethnopharmacology JID - 7903310 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - 0 (DNA-Binding Proteins) RN - 0 (Membrane Glycoproteins) RN - 0 (Nerve Tissue Proteins) RN - 0 (NeuN protein, mouse) RN - 0 (Neuroprotective Agents) RN - 0 (Nuclear Proteins) RN - 0 (Plant Extracts) RN - 178AQM8R56 (isochlorogenic acid) RN - 318ADP12RI (Chlorogenic Acid) RN - EC 2.6.1.1 (Aspartate Aminotransferases) RN - EC 2.6.1.2 (Alanine Transaminase) RN - EC 2.7.10.1 (Ntrk2 protein, mouse) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) RN - W980KJ009P (Corticosterone) SB - IM MH - Alanine Transaminase/blood MH - Animals MH - Aspartate Aminotransferases/blood MH - Behavior, Animal/drug effects MH - Brain/drug effects/metabolism/pathology MH - Brain-Derived Neurotrophic Factor/metabolism MH - Cell Line, Tumor MH - Cell Survival/drug effects MH - Chlorogenic Acid/analogs & derivatives/analysis/therapeutic use MH - Corticosterone/blood MH - Cyclic AMP Response Element-Binding Protein/metabolism MH - DNA-Binding Proteins MH - Fatigue/blood/*drug therapy MH - Humans MH - *Magnoliopsida MH - Male MH - Membrane Glycoproteins/metabolism MH - Mice MH - Mice, Inbred C57BL MH - Nerve Tissue Proteins/metabolism MH - Neuroprotective Agents/analysis/*therapeutic use MH - Nuclear Proteins/metabolism MH - Plant Extracts/analysis/*therapeutic use MH - Protein-Tyrosine Kinases/metabolism MH - Rats MH - Restraint, Physical MH - Stress, Psychological/blood/*drug therapy OTO - NOTNLM OT - Akebia quinata Decaisne OT - Fatigue OT - Mibyeong OT - Neuroprotective OT - Restraint stress EDAT- 2018/04/10 06:00 MHDA- 2018/10/17 06:00 CRDT- 2018/04/10 06:00 PHST- 2017/08/31 00:00 [received] PHST- 2018/01/31 00:00 [revised] PHST- 2018/04/05 00:00 [accepted] PHST- 2018/04/10 06:00 [pubmed] PHST- 2018/10/17 06:00 [medline] PHST- 2018/04/10 06:00 [entrez] AID - S0378-8741(17)33257-9 [pii] AID - 10.1016/j.jep.2018.04.010 [doi] PST - ppublish SO - J Ethnopharmacol. 2018 Aug 10;222:270-279. doi: 10.1016/j.jep.2018.04.010. Epub 2018 Apr 6.