title: The herbal extract KCHO-1 exerts a neuroprotective effect by ameliorating oxidative stress via heme oxygenase-1 upregulation.
abstract: KCHO-1 is a novel product comprised of 30% ethanol extracts obtained from nine medical herbs, which are commonly used in traditional Korean and Chinese medicine. The nine herbs include Curcuma longa, Salvia miltiorrhiza, Gastrodia elata, Chaenomeles sinensis, Polygala tenuifolia, Paeonia japonica, Glycyrrhiza uralensis, Atractylodes japonica and processed Aconitum carmichaeli. Recent studies have reported the beneficial effects of these herbs. The present study aimed to investigate the direct neuroprotective effects of KCHO‑1 on HT22 mouse hippocampal cells, and to determine the possible underlying mechanisms. KCHO‑1 significantly suppressed glutamate‑ and hydrogen peroxide (H2O2)‑induced cell damage, and reactive oxygen species generation. In addition, KCHO‑1 increased the mRNA and protein expression levels of heme oxygenase (HO)‑1. Tin protoporphyrin, which is an inhibitor of HO activity, partially suppressed the effects of KCHO‑1. Furthermore, KCHO‑1 significantly upregulated nuclear factor erythroid‑derived 2‑related factor‑2 (Nrf2) nuclear translocation. Extracellular signal‑regulated kinase (ERK) activation also appeared to be associated with KCHO‑1‑induced HO‑1 expression, since the ERK inhibitor PD98059 suppressed HO‑1 expression and prevented KCHO‑1‑induced cytoprotection. The results of the present study suggested that KCHO‑1 may effectively prevent glutamate‑ or H2O2‑induced oxidative damage via Nrf2/ERK mitogen‑activated protein kinase‑dependent HO‑1 expression. These data suggest that KCHO‑1 may be useful for the treatment of neurodegenerative diseases.
authors.affiliation: Department of Pharmacy, Chosun University, Dong‑gu, Gwangju 61452, Republic of Korea.
authors.forename: Dong-Sung
authors.initials: DS
authors.lastname: Lee
authors.affiliation: Department of Pharmacy, Wonkwang University, Jeollabuk‑do 54538, Republic of Korea.
authors.forename: Wonmin
authors.initials: W
authors.lastname: Ko
authors.affiliation: Department of Internal Medicine, School of Oriental Medicine, Wonkwang University, Iksan, Jeollabuk‑do 54538, Republic of Korea.
authors.forename: Bong-Keun
authors.initials: BK
authors.lastname: Song
authors.affiliation: Department of Neurology, Inam Neuroscience Research Center, Sanbon Medical Center, College of Medicine, Wonkwang University, Iksan, Jeollabuk‑do 54538, Republic of Korea.
authors.forename: Ilhong
authors.initials: I
authors.lastname: Son
authors.affiliation: Center of Integrative Medicine, Department of Internal Medicine, Wonkwang University Gwangju Hospital, Gwangju 61729, Republic of Korea.
authors.forename: Dong-Woung
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Hanbang Body‑Fluid Research Center, Wonkwang University, Iksan, Jeollabuk‑do 54538, Republic of Korea.
authors.forename: Dae-Gil
authors.initials: DG
authors.lastname: Kang
authors.affiliation: Hanbang Body‑Fluid Research Center, Wonkwang University, Iksan, Jeollabuk‑do 54538, Republic of Korea.
authors.forename: Ho-Sub
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Department of Pharmacy, Wonkwang University, Jeollabuk‑do 54538, Republic of Korea.
authors.forename: Hyuncheol
authors.initials: H
authors.lastname: Oh
authors.affiliation: Department of Biochemistry, Inha University School of Medicine, Incheon 22212, Republic of Korea.
authors.forename: Jun-Hyeog
authors.initials: JH
authors.lastname: Jang
authors.affiliation: Department of Pharmacy, Wonkwang University, Jeollabuk‑do 54538, Republic of Korea.
authors.forename: Youn-Chul
authors.initials: YC
authors.lastname: Kim
authors.affiliation: ALS/MND Center of Wonkwang University Korean Medical Hospital, Gwangju 61729, Republic of Korea.
authors.forename: Sungchul
authors.initials: S
authors.lastname: Kim
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D018698:Glutamic Acid / Q000378:metabolism / Q000494:pharmacology; D051547:Heme Oxygenase-1 / Q000235:genetics*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D018698:Glutamic Acid; D006861:Hydrogen Peroxide; D051547:Heme Oxygenase-1