YGS40, an active fraction of Yi-Gan San, reduces hydrogen peroxide-induced apoptosis in PC12 cells

doi:10.1016/S1875-5364(15)30037-6

Chinese Journal of Natural Medicines

Volume 13, Issue 6, June 2015, Pages 438-444

https://doi.org/10.1016/S1875-5364(15)30037-6 Get rights and content

Abstract

In our previous study, we have elucidated the chemical profile of YGS40, a fraction of Yi-Gan San (YGS), used for the treatment of Alzheimer's disease (AD). Oxidative stress-induced apoptosis is implicated in neurodegenerative disorders such as AD. The aim of the present study was to explore the protective effects of YGS40 against hydrogen peroxide (H₂O₂)-induced apoptosis in PC12 cells and the underlying mechanisms. PC12 cells were exposed to 100 μmol·L⁻¹ of H₂O₂ for 12 h with or without YGS40 pretreatment. Cytotoxicity was determined by MTT (3, (4, 5-dimethylthiazole-2-yl) 2, 5-diphenyl-tetrazolium bromide) and lactate dehydrogenase (LDH) release assays; apoptosis was detected by Annexin V/propidium iodide coupled staining and by determining caspase-3 activity and Bax and Bcl-2 protein levels. Mitochondrial membrane potential (MMP) was assessed by the retention of rhodamine123; and the activities of superoxide dismutase (SOD) and malondialdehyde (MDA) were measured using commercially available enzymatic kits. Pretreatment with YGS40 significantly prevented H₂O₂-induced cytotoxicity and protected the cells against H₂O₂-triggered apoptosis characterized by externalization of membrane phosphatidylserine and caspase-3 activation and the increased ratio of Bax/Bcl-2 in PC12 cells. Further studies showed that YGS40 suppressed H₂O₂-induced MMP loss, increased SOD activity, and decreased MDA level. These findings suggest that YGS40 may be beneficial for the prevention and treatment of oxidative stress-mediated disorders.

Previously we have elucidated the chemical profile of YGS40. In this study, we investigated the protective effects of YGS40 on H₂O₂-induce apoptosis in PC12 cells. The results showed that YGS40 could prevent H₂O₂-induced apoptosis, which is implicated in neurodegenerative disorders such as Alzheimer's disease. These findings suggest that YGS40 may be beneficial for the prevention and treatment of oxidative stress-induced disorders.

References (24)

V Chauhan et al.
Oxidative stress in Alzheimer's disease [J]
Pathophysiology
(2006)
EM Jeong et al.
Metabolic stress, reactive oxygen species, and arrhythmia [J]
J Mol Cellul Cardiol
(2012)
ML Circu et al.
Reactive oxygen species, cellular redox systems, and apoptosis [J]
Free Rad Biol Med
(2010)
Z Kawakami et al.
Yokukansan, a kampo medicine, protects against glutamate cytotoxicity due to oxidative stress in PC12 cells [J]
J ethnopharmacol
(2011)
H Chen et al.
Chemical profile of the active fraction of Yi-Gan San by HPLC-DAD-Q-TOF-MS and its neuroprotective effect against glutamate-induced cytotoxicity [J]
Chin J Nat Med
(2014)
H Hong et al.
Protection against hydrogen peroxide- induced cytotoxicity in PC12 cells by scutellarin [J]
Life Sci
(2004)
JH Jang et al.
Protective effect of resveratrol on β-amyloid-induced oxidative PC12 cell death [J]
Free Radic Biol Med
(2003)
M Tripathi et al.
Glycyrrhizic acid modulates t-BHP induced apoptosis in primary rat hepatocytes [J]
Food Chem Toxicol
(2009)
JS Shim et al.
Effects of the hook of Uncaria rhynchophylla on neurotoxicity in the 6-hydroxydopamine model of Parkinson's disease [J]
J Ethnopharmacol
(2009)
AR Sudheer et al.
Protective effect of ferulic acid on nicotine-induced DNA damage and cellular changes in cultured rat peripheral blood lymphocytes: a comparison with N-acetylcysteine [J]
Toxicol In Vitro
(2007)

ES Cho et al.

Attenuation of oxidative neuronal cell death by coffee phenolic phytochemicals [J]

Mutat Res/Fundament Molecul Mechanis Mutagene

(2009)

SH Kwon et al.

Eucommia ulmoides Oliv. Bark. protects against hydrogen peroxide-induced neuronal cell death in SH-SY5Y cells [J]

J Ethnopharmacol

(2012)

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One of its components, Uncaria sinensis, also has been shown to prevent neuronal death induced by glutamate, possibly by inhibiting Ca2+ influx [78]. YGS40, an active component of yi-gan san, also reduces apoptosis triggered by hydrogen-peroxide [79]. An open-label study with 22 TD patients showed significant reduction of AIMS scores from baseline (12.1 ± 2.2 to 1.6 ± 1.3, p < 0.0001) after 12-week treatment of 7.5 g/day of yi-gan san [80].
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Available online 20 June 2015

Research funding This work was supported by the National Natural Science Foundation of China (Nos. 81274046 and 81373956).

These authors have no conflict of interest to declare.

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YGS40, an active fraction of Yi-Gan San, reduces hydrogen peroxide-induced apoptosis in PC12 cells

Abstract

Pathophysiology

J Mol Cellul Cardiol

Free Rad Biol Med

J ethnopharmacol

Chin J Nat Med

Life Sci

Free Radic Biol Med

Food Chem Toxicol

J Ethnopharmacol

Toxicol In Vitro

Mutat Res/Fundament Molecul Mechanis Mutagene

J Ethnopharmacol