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Title: 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

Abstract

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 Gbeta1/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 Gbeta1/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.

Authors:
 [1];  [2];  [1];  [2]
  1. College of Pharmacy, Chungnam National University, Daejeon (Korea, Republic of)
  2. (Korea, Republic of)
Publication Date:
OSTI Identifier:
21344822
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 242; Journal Issue: 1; Other Information: DOI: 10.1016/j.taap.2009.09.009; PII: S0041-008X(09)00398-6; Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANTIOXIDANTS; APOPTOSIS; DOPAMINE; DRUGS; ESTROGENS; HEME; HERBS; MEN; OXIDATION; OXYGENASES; RECEPTORS; STRESSES; TOXICITY; TOXINS; AMINES; ANIMALS; ANTIGENS; AROMATICS; AUTONOMIC NERVOUS SYSTEM AGENTS; CARBOXYLIC ACIDS; CARDIOTONICS; CARDIOVASCULAR AGENTS; CHEMICAL REACTIONS; ENZYMES; HAZARDOUS MATERIALS; HETEROCYCLIC ACIDS; HETEROCYCLIC COMPOUNDS; HORMONES; HYDROXY COMPOUNDS; MALES; MAMMALS; MAN; MATERIALS; MEMBRANE PROTEINS; NEUROREGULATORS; ORGANIC ACIDS; ORGANIC COMPOUNDS; ORGANIC NITROGEN COMPOUNDS; OXIDOREDUCTASES; PHENOLS; PIGMENTS; PLANTS; POLYPHENOLS; PORPHYRINS; PRIMATES; PROTEINS; STEROID HORMONES; SYMPATHOMIMETICS; TOXIC MATERIALS; VERTEBRATES

Citation Formats

Hwang, Yong Pil, College of Pharmacy, Chosun University, Gwangju, Jeong, Hye Gwang, E-mail: hgjeong@cnu.ac.k, and College of Pharmacy, Chosun University, Gwangju. 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. United States: N. p., 2010. Web. doi:10.1016/j.taap.2009.09.009.
Hwang, Yong Pil, College of Pharmacy, Chosun University, Gwangju, Jeong, Hye Gwang, E-mail: hgjeong@cnu.ac.k, & College of Pharmacy, Chosun University, Gwangju. 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. United States. doi:10.1016/j.taap.2009.09.009.
Hwang, Yong Pil, College of Pharmacy, Chosun University, Gwangju, Jeong, Hye Gwang, E-mail: hgjeong@cnu.ac.k, and College of Pharmacy, Chosun University, Gwangju. Fri . "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". United States. doi:10.1016/j.taap.2009.09.009.
@article{osti_21344822,
title = {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},
author = {Hwang, Yong Pil and College of Pharmacy, Chosun University, Gwangju and Jeong, Hye Gwang, E-mail: hgjeong@cnu.ac.k and College of Pharmacy, Chosun University, Gwangju},
abstractNote = {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 Gbeta1/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 Gbeta1/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.},
doi = {10.1016/j.taap.2009.09.009},
journal = {Toxicology and Applied Pharmacology},
number = 1,
volume = 242,
place = {United States},
year = {Fri Jan 01 00:00:00 EST 2010},
month = {Fri Jan 01 00:00:00 EST 2010}
}