Ginsenoside Rb1 protects against 6-hydroxydopamine-induced oxidative stress by increasing heme oxygenase-1 expression through an estrogen receptor-related PI3K/Akt/Nrf2-dependent pathway in human dopaminergic cells

• Published in: Toxicology and applied pharmacology Vol. 242; no. 1; pp. 18 - 28
• Main Authors: Hwang, Yong Pil, Jeong, Hye Gwang
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 2010; Elsevier
• Subjects: 60 APPLIED LIFE SCIENCES; AMINES; ANIMALS; ANTIGENS; ANTIOXIDANTS; APOPTOSIS; Araliaceae; AROMATICS; AUTONOMIC NERVOUS SYSTEM AGENTS; Biological and medical sciences; CARBOXYLIC ACIDS; CARDIOTONICS; CARDIOVASCULAR AGENTS; Caspase 3 - metabolism; Caspase 9 - metabolism; Cell Line, Tumor; Cell Survival - drug effects; CHEMICAL REACTIONS; Cytoprotection; DOPAMINE; Dopamine - physiology; DRUGS; ENZYMES; Estrogen receptor; ESTROGENS; Ginsenoside Rb1; Ginsenosides - pharmacology; HAZARDOUS MATERIALS; HEME; Heme oxygenase-1; Heme Oxygenase-1 - biosynthesis; HERBS; HETEROCYCLIC ACIDS; HETEROCYCLIC COMPOUNDS; HORMONES; Humans; HYDROXY COMPOUNDS; Immunohistochemistry; In Situ Nick-End Labeling; MALES; MAMMALS; MAN; MATERIALS; Medical sciences; MEMBRANE PROTEINS; MEN; NEUROREGULATORS; NF-E2 related factor 2; NF-E2-Related Factor 2 - metabolism; Oncogene Protein v-akt - metabolism; ORGANIC ACIDS; ORGANIC COMPOUNDS; ORGANIC NITROGEN COMPOUNDS; OXIDATION; Oxidative Stress - drug effects; Oxidopamine - antagonists & inhibitors; Oxidopamine - toxicity; OXIDOREDUCTASES; OXYGENASES; Panax ginseng; PHENOLS; Phosphatidylinositol 3-kinase; Phosphatidylinositol 3-Kinases - metabolism; PIGMENTS; PLANTS; POLYPHENOLS; PORPHYRINS; PRIMATES; PROTEINS; Reactive Oxygen Species - metabolism; RECEPTORS; Receptors, Estrogen - physiology; Reverse Transcriptase Polymerase Chain Reaction; RNA - biosynthesis; RNA - genetics; STEROID HORMONES; STRESSES; SYMPATHOMIMETICS; TOXIC MATERIALS; TOXICITY; Toxicology; TOXINS; Transfection; VERTEBRATES; Estrogen receptor; Phosphatidylinositol 3-kinase; Ginsenoside Rb1; NF-E2 related factor 2; Heme oxygenase-1; Cytoprotection; Human; Transcription factor NF-E2; Oxidative stress; Retinoblastoma gene; Enzyme; Transferases; Akt protein kinase; Heme oxygenase (decyclizing); 1-Phosphatidylinositol 3-kinase; Prevention; Cytoprotector; Heat shock protein; Oxidoreductases; Tumor suppressor gene; Hormonal receptor
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/j.taap.2009.09.009

Phytoestrogens are polyphenolic non-steroidal plant compounds with estrogen-like biological activity. Ginseng, the root of
Panax ginseng C.A. Meyer (Araliaceae), is a popular traditional herbal medicine. Ginsenoside Rb1 (Rb1), an active component commonly found in ginseng root, is a phytoestrogen that exerts estrogen-like activity. In this study, we demonstrate that the phytoestrogen Rb1 inhibits 6-hydroxydopamine (6-OHDA)-induced oxidative injury via an ER-dependent Gβ1/PI3K/Akt and heme oxygenase-1 (HO-1) pathway. Pretreatment of SH-SY5Y cells with Rb1 significantly reduced 6-OHDA-induced caspase-3 activation and subsequent cell death. Rb1 also up-regulated HO-1 expression, which conferred cytoprotection against 6-OHDA-induced oxidative injury. Moreover, Rb1 induced both Nrf2 nuclear translocation, which is upstream of HO-1 expression and PI3K activation, a pathway that is involved in induced Nrf2 nuclear translocation, HO-1 expression and cytoprotection. Also, Rb1-mediated increases in PI3K activation and HO-1 induction were reversed by co-treatment with ICI 182,780 and pertussis toxin. Taken together, these results suggest that Rb1 augments the cellular antioxidant defenses through ER-dependent HO-1 induction via the Gβ1/PI3K/Akt-Nrf2 signaling pathway, thereby protecting cells from oxidative stress. Thus our study indicates that Rb1 has a partial cytoprotective role in dopaminergic cell culture systems.