title: Ginsenoside Rb1 directly scavenges hydroxyl radical and hypochlorous acid.
abstract: Reactive oxygen species (ROS) have been implicated in a variety of inflammatory diseases including cardiovascular disease (CVD), cancer, diabetes, Alzheimer's disease, autism, cataracts and aging. When endogenous mechanisms for the maintenance of redox homeostasis are overwhelmed, dietary intake of antioxidants contributes substantially to balancing the body's oxidant/antioxidant status. Ginsenosides are thought to be primarily responsible for the pharmacological effect of P. ginseng root extracts on oxidative stress and inflammation. However, little is known about the underlying antioxidant mechanisms of individual ginsenoside; specifically, the reactivity of ginsenoside Rb1 with ROS has not been well studied. We found that Rb1 can significantly and selectively reduce hydroxyl radical (●OH) and hypochlorous acid (HOCl), two of the strongest ROS, with unique molecular mechanisms in a cell-free system. Rb1 directly scavenges the ●OH and protects plasmid DNA from damage induced by ●OH. ●OH likely attacks the double bond on the side chain of Rb1 as well as hydrogen atoms adjacent to the -OH groups, including those of sugar moieties. Rb1 also shows a high reactivity to HOCl and effectively inhibits HOCl-induced tyrosine chlorination in a cell free system. HOCl is added to the double bond of Rb1; the -Cl group and -OH group of HOCl possibly bond at C-24 and C-25 of Rb1 based on the regioselectivity of Markovnikov's Rule. To our knowledge, this is the first demonstration that ginsenoside Rb1 scavenges HOCl and protects tyrosine from HOCl-induced chlorination. Thus, this study reveals unique antioxidant mechanisms of individual ginsenoside Rb1, which may contribute to the pharmacological effect of P. ginseng and to the development of effective strategies for clinical applications of ginsenosides.
authors.affiliation: Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Jian-Ming
authors.initials: JM
authors.lastname: Lü
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Weakley
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yang
authors.forename: Ming
authors.initials: M
authors.lastname: Hu
authors.forename: Qizhi
authors.initials: Q
authors.lastname: Yao
authors.forename: Changyi
authors.initials: C
authors.lastname: Chen
mesh_terms: D002474:Cell-Free System; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000378:metabolism / Q000494:pharmacology*; D036145:Ginsenosides / Q000378:metabolism / Q000494:pharmacology*; D017665:Hydroxyl Radical / Q000378:metabolism*; D006997:Hypochlorous Acid / Q000378:metabolism*; D013058:Mass Spectrometry; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D014443:Tyrosine / Q000378:metabolism
chemical_list: D016166:Free Radical Scavengers; D036145:Ginsenosides; D017665:Hydroxyl Radical; D014443:Tyrosine; D006997:Hypochlorous Acid; C442759:ginsenoside Rb1