title: Sailuotong Prevents Hydrogen Peroxide (H₂O₂)-Induced Injury in EA.hy926 Cells.
abstract: Sailuotong (SLT) is a standardised three-herb formulation consisting ofPanax ginseng,Ginkgo biloba, andCrocus sativusdesigned for the management of vascular dementia. While the latest clinical trials have demonstrated beneficial effects of SLT in vascular dementia, the underlying cellular mechanisms have not been fully explored. The aim of this study was to assess the ability and mechanisms of SLT to act against hydrogen peroxide (H₂O₂)-induced oxidative damage in cultured human vascular endothelial cells (EAhy926). SLT (1-50 µg/mL) significantly suppressed the H₂O₂-induced cell death and abolished the H₂O₂-induced reactive oxygen species (ROS) generation in a concentration-dependent manner. Similarly, H₂O₂ (0.5 mM; 24 h) caused a ~2-fold increase in lactate dehydrogenase (LDH) release from the EA.hy926 cells which were significantly suppressed by SLT (1-50 µg/mL) in a concentration-dependent manner. Incubation of SLT (50 µg/mL) increased superoxide dismutase (SOD) activity and suppressed the H₂O₂-enhanced Bax/Bcl-2 ratio and cleaved caspase-3 expression. In conclusion, our results suggest that SLT protects EA.hy916 cells against H₂O₂-mediated injury via direct reduction of intracellular ROS generation and an increase in SOD activity. These protective effects are closely associated with the inhibition of the apoptotic death cascade via the suppression of caspase-3 activation and reduction of Bax/Bcl-2 ratio, thereby indicating a potential mechanism of action for the clinical effects observed.
authors.affiliation: National Institute of Complementary Medicine (NICM), Western Sydney University, Penrith, NSW 2571, Australia. s.seto@westernsydeny.edu.au.
authors.forename: Sai Wang
authors.initials: SW
authors.lastname: Seto
authors.affiliation: National Institute of Complementary Medicine (NICM), Western Sydney University, Penrith, NSW 2571, Australia. d.chang@westernsydney.edu.au.
authors.forename: Dennis
authors.initials: D
authors.lastname: Chang
authors.affiliation: National Institute of Complementary Medicine (NICM), Western Sydney University, Penrith, NSW 2571, Australia. i.ko@westernsydney.edu.au.
authors.forename: Wai Man
authors.initials: WM
authors.lastname: Ko
authors.affiliation: National Institute of Complementary Medicine (NICM), Western Sydney University, Penrith, NSW 2571, Australia. P.Zhou@westernsydney.edu.au.
authors.forename: Xian
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Faculty of Medicine, University of New South Wales, NSW 2052, Australia. hosen.kiat@chi.org.au.|School of Medicine, Western Sydney University, Locked Bag 1797, Penrith, NSW 2751, Australia. hosen.kiat@chi.org.au.|Faculty of Medicine and Health Sciences, Macquarie University, NSW 2109, Australia. hosen.kiat@chi.org.au.
authors.forename: Hosen
authors.initials: H
authors.lastname: Kiat
authors.affiliation: National Institute of Complementary Medicine (NICM), Western Sydney University, Penrith, NSW 2571, Australia. A.Bensoussan@westernsydney.edu.au.
authors.forename: Alan
authors.initials: A
authors.lastname: Bensoussan
authors.affiliation: State Key Laboratory Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Macao, China. simonlee@umac.mo.
authors.forename: Simon M Y
authors.initials: SM
authors.lastname: Lee
authors.affiliation: State Key Laboratory Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Macao, China. maghoi@umac.mo.
authors.forename: Maggie P M
authors.initials: MP
authors.lastname: Hoi
authors.affiliation: National Institute of Complementary Medicine (NICM), Western Sydney University, Penrith, NSW 2571, Australia. G.Steiner@westernsydney.edu.au.
authors.forename: Genevieve Z
authors.initials: GZ
authors.lastname: Steiner
authors.affiliation: National Institute of Complementary Medicine (NICM), Western Sydney University, Penrith, NSW 2571, Australia. Jianxun.Liu@westernsydney.edu.au.|Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China. Jianxun.Liu@westernsydney.edu.au.
authors.forename: Jianxun
authors.initials: J
authors.lastname: Liu
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D004365:Drugs, Chinese Herbal; D016877:Oxidants; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; C000603038:sailuotong; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase; D053148:Caspase 3
keywords: Sailuotong (SLT); apoptosis; endothelial dysfunction; herbal medicine; reactive oxygen species; vascular dementia