Amauroderma rugosum Protects PC12 Cells against 6-OHDA-Induced Neurotoxicity through Antioxidant and Antiapoptotic Effects

Amauroderma rugosum (AR) is a dietary mushroom in the Ganodermataceae family whose pharmacological activity and medicinal value have rarely been reported. In this study, the antioxidant capacity and neuroprotective effects of AR were investigated. The aqueous extract of AR was confirmed to contain phenolic compounds, polysaccharides, and triterpenes. The results of 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) and total antioxidant capacity assays revealed that AR extract scavenged reactive oxygen species. Moreover, AR extract decreased the cytotoxicity, oxidative stress, mitochondrial dysfunction, and apoptosis of PC12 cells induced by 6-hydroxydopamine (6-OHDA). In addition, 6-OHDA upregulated the expressions of proapoptotic proteins and downregulated the Akt (protein kinase B)/mTOR- (mammalian target of rapamycin-) and MEK (mitogen-activated protein kinase kinase)/ERK- (extracellular signal-regulated kinases-) dependent signaling pathways. These effects of 6-OHDA were abolished or partially reversed by AR extract. Furthermore, the neuroprotective effects of AR in 6-OHDA-treated PC12 cells were significantly abolished by Akt and MEK inhibitor. Thus, AR extract possesses neuroprotective effects, probably through its antioxidant and antiapoptotic effects. These findings suggest the potential application of AR in the prevention or treatment of oxidative stress-related neurodegenerative diseases such as Parkinson's disease.

[1]  P. Niedzielski,et al.  The Effect of Mushroom Extracts on Human Platelet and Blood Coagulation: In vitro Screening of Eight Edible Species , 2019, Nutrients.

[2]  L. Di,et al.  Tetramethylpyrazine Analogue T-006 Exerts Neuroprotective Effects against 6-Hydroxydopamine-Induced Parkinson's Disease In Vitro and In Vivo , 2019, Oxidative medicine and cellular longevity.

[3]  Zhejie Chen,et al.  Dietary compound glycyrrhetinic acid suppresses tumor angiogenesis and growth by modulating antiangiogenic and proapoptotic pathways in vitro and in vivo. , 2019, The Journal of nutritional biochemistry.

[4]  Fan Tang,et al.  AGS-30, an andrographolide derivative, suppresses tumor angiogenesis and growth in vitro and in vivo. , 2019, Biochemical pharmacology.

[5]  Yihan Wu,et al.  Oridonin synergistically enhances the anti-tumor efficacy of doxorubicin against aggressive breast cancer via pro-apoptotic and anti-angiogenic effects. , 2019, Pharmacological research.

[6]  Jia-Yi Li,et al.  Lactoferrin ameliorates dopaminergic neurodegeneration and motor deficits in MPTP-treated mice , 2018, Redox biology.

[7]  K. Misra,et al.  Phenolic Rich Fractions from Mycelium and Fruiting Body of Ganoderma lucidum Inhibit Bacterial Pathogens Mediated by Generation of Reactive Oxygen Species and Protein Leakage and Modulate Hypoxic Stress in HEK 293 Cell Line , 2018, Advances in pharmacological sciences.

[8]  M. Zhou,et al.  Ganoderma lucidum extract ameliorates MPTP-induced parkinsonism and protects dopaminergic neurons from oxidative stress via regulating mitochondrial function, autophagy, and apoptosis , 2018, Acta Pharmacologica Sinica.

[9]  Xiao-Liang Liu,et al.  Damage to dopaminergic neurons by oxidative stress in Parkinson's disease (Review). , 2018, International journal of molecular medicine.

[10]  Yitao Wang,et al.  pH-sensitive polymeric nanoparticles for co-delivery of doxorubicin and curcumin to treat cancer via enhanced pro-apoptotic and anti-angiogenic activities. , 2017, Acta biomaterialia.

[11]  F. Erim,et al.  Total phenolic contents, antioxidant activities, and bioactive ingredients of juices from pomegranate cultivars worldwide. , 2017, Food chemistry.

[12]  Peng Li,et al.  Berberine protects against 6-OHDA-induced neurotoxicity in PC12 cells and zebrafish through hormetic mechanisms involving PI3K/AKT/Bcl-2 and Nrf2/HO-1 pathways , 2016, Redox biology.

[13]  K. Chua,et al.  Attenuation of Inflammatory Mediators (TNF-α and Nitric Oxide) and Up-Regulation of IL-10 by Wild and Domesticated Basidiocarps of Amauroderma rugosum (Blume & T. Nees) Torrend in LPS-Stimulated RAW264.7 Cells , 2015, PloS one.

[14]  J. Blesa,et al.  Oxidative stress and Parkinson’s disease , 2015, Front. Neuroanat..

[15]  Mei-Hsien Lee,et al.  Neurocytoprotective Effects of Aliphatic Hydroxamates from Lovastatin, a Secondary Metabolite from Monascus-Fermented Red Mold Rice, in 6-Hydroxydopamine (6-OHDA)-Treated Nerve Growth Factor (NGF)-Differentiated PC12 Cells. , 2015, ACS chemical neuroscience.

[16]  Jiri Polivka,et al.  Molecular targets for cancer therapy in the PI3K/AKT/mTOR pathway. , 2014, Pharmacology & therapeutics.

[17]  Yifan Han,et al.  The Novel Tetramethylpyrazine Bis-nitrone (TN-2) Protects Against MPTP/MPP+-Induced Neurotoxicity via Inhibition of Mitochondrial-Dependent Apoptosis , 2014, Journal of Neuroimmune Pharmacology.

[18]  V. Sabaratnam,et al.  Amauroderma rugosum (Blume & T. Nees) Torrend: Nutritional Composition and Antioxidant and Potential Anti-Inflammatory Properties , 2013, Evidence-based complementary and alternative medicine : eCAM.

[19]  M. Chesselet,et al.  Mitochondrial dysfunction and oxidative stress in Parkinson's disease , 2013, Progress in Neurobiology.

[20]  O. Hwang.  Role of Oxidative Stress in Parkinson's Disease , 2013, Experimental neurobiology.

[21]  Hyung-Ryong Kim,et al.  An Involvement of Oxidative Stress in Endoplasmic Reticulum Stress and Its Associated Diseases , 2012, International journal of molecular sciences.

[22]  A. Federico,et al.  Mitochondria, oxidative stress and neurodegeneration , 2012, Journal of the Neurological Sciences.

[23]  R. Wong,et al.  Neuroprotective effect of preadministration with Ganoderma lucidum spore on rat hippocampus. , 2012, Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie.

[24]  Yifan Han,et al.  Baicalein protects against 6-OHDA-induced neurotoxicity through activation of Keap1/Nrf2/HO-1 and involving PKCα and PI3K/AKT signaling pathways. , 2012, Journal of agricultural and food chemistry.

[25]  O. Firuzi,et al.  Antioxidant therapy: current status and future prospects. , 2011, Current medicinal chemistry.

[26]  L. Greene,et al.  RTP801 Is Induced in Parkinson's Disease and Mediates Neuron Death by Inhibiting Akt Phosphorylation/Activation , 2008, The Journal of Neuroscience.

[27]  Nicola J. Ray,et al.  Local field potential beta activity in the subthalamic nucleus of patients with Parkinson's disease is associated with improvements in bradykinesia after dopamine and deep brain stimulation , 2008, Experimental Neurology.

[28]  E. Kavanagh,et al.  Functionality of NGF-protected PC12 cells following exposure to 6-hydroxydopamine. , 2006, Biochemical and biophysical research communications.

[29]  Howard L McLeod,et al.  PI3K/Akt/mTOR pathway as a target for cancer therapy , 2005, Anti-cancer drugs.

[30]  D. Sliva,et al.  Ganoderma Lucidum(Reishi) in Cancer Treatment , 2003, Integrative cancer therapies.

[31]  Carla Perrone-Capano,et al.  Chronic activation of ERK and neurodegenerative diseases , 2003, BioEssays : news and reviews in molecular, cellular and developmental biology.

[32]  W. Dauer,et al.  Parkinson's Disease Mechanisms and Models , 2003, Neuron.

[33]  E. Melamed,et al.  Apoptosis and Parkinson's disease , 2003, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[34]  I. Kirkinezos,et al.  Reactive oxygen species and mitochondrial diseases. , 2001, Seminars in cell & developmental biology.

[35]  J. Dichgans,et al.  Rescue from death but not from functional impairment: caspase inhibition protects dopaminergic cells against 6‐hydroxydopamine‐induced apoptosis but not against the loss of their terminals , 2001, Journal of neurochemistry.

[36]  E. Hirsch,et al.  Caspase-8 Is an Effector in Apoptotic Death of Dopaminergic Neurons in Parkinson's Disease, But Pathway Inhibition Results in Neuronal Necrosis , 2001, The Journal of Neuroscience.

[37]  E. Hirsch,et al.  Caspase-3: A vulnerability factor and final effector in apoptotic death of dopaminergic neurons in Parkinson's disease. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[38]  M. Woodward,et al.  Dietary antioxidant vitamins and fiber in the etiology of cardiovascular disease and all-causes mortality: results from the Scottish Heart Health Study. , 1999, American journal of epidemiology.

[39]  A. Hofman,et al.  Dietary antioxidants and Parkinson disease. The Rotterdam Study. , 1997, Archives of neurology.

[40]  Michael E. Greenberg,et al.  Opposing Effects of ERK and JNK-p38 MAP Kinases on Apoptosis , 1995, Science.

[41]  E. Rimm,et al.  Vitamin E consumption and the risk of coronary heart disease in men. , 1993, The New England journal of medicine.

[42]  Zhibin Lin,et al.  Antioxidative and Free Radical Scavenging Activity of Ganoderma (Lingzhi). , 2019, Advances in experimental medicine and biology.