Therapeutic effects of paeonol on methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid-induced Parkinson's disease in mice

Shi, Xiaojin; Chen, Yu‐Hua; Líu, Hao; Qu, Hongdang

doi:10.3892/mmr.2016.5573

Cited by 49 publications

(27 citation statements)

References 54 publications

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“…injection of TAK242 (3 mg/kg; TLR4 antagonist) 1 hour before the LPS injection (LPS 1 TAK242). The doses of LPS and paeonol were determined from the literature (Hsieh et al, 2006;Lee et al, 2013;Shi et al, 2016) and preliminary data (Supplemental Fig. 1, A and B), which showed that 20 mg/kg paeonol improved relaxation in response to the endothelium-dependent vasodilator acetylcholine in mice treated with LPS (15 mg/kg).…”

Section: Methodsmentioning

confidence: 99%

Paeonol Attenuates LPS-Induced Endothelial Dysfunction and Apoptosis by Inhibiting BMP4 and TLR4 Signaling Simultaneously but Independently

Choy

Lau

Murugan

et al. 2017

J Pharmacol Exp Ther

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Inflammatory injury of the endothelium leads to apoptosis and endothelial dysfunction. The current study explored the effect and mechanisms of paeonol in inflammation-induced apoptosis and endothelial dysfunction induced by lipopolysaccharides (LPSs). The effects of paeonol on LPS-induced inflammatory injury were assessed by Western blotting, flow cytometry and reactive oxygen species (ROS) measurement in human umbilical vein endothelial cells (HUVECs) and C57BL/6J mice. Vascular reactivity of isolated mouse aortae was examined using wire myographs. The exposure of HUVECs to LPS increased the protein presence of Toll-like receptor 4 (TLR4), bone morphogenic protein 4 (BMP4), BMP receptor type 1A, nicotinamide adenine dinucleotide phosphate oxidase subunit 2, mitogen-activated protein kinase (MAPK), inducible nitric oxide synthase (iNOS), and cleaved caspase 3, as well as decreased it in phosphorylated endothelial nitric oxide synthase; these effects were prevented by treatment with paeonol. Similarly, cotreatment with paeonol reversed BMP4-induced apoptosis in HUVECs. Relaxation in response to the endothelium-dependent vasodilator acetylcholine were impaired in mouse aortae after exposure to LPSs; this endothelial dysfunction was reversed by cotreatment with paeonol, noggin (a BMP4 inhibitor), TAK242 (TLR4 antagonist), apocynin (an ROS scavenger), MAPK inhibitors, and AG (an iNOS inhibitor). BMP4 small interfering RNAs (siRNAs) abolished LPS-induced upregulation of BMP4 and cleaved caspase 3 protein, but not in cells treated with TLR4 siRNA and vice versa. The silencing of TLR4 and BMP4 abolished the inhibitory effects of paeonol on LPS-induced activation of cleaved caspase 3. The present results demonstrate that paeonol reduces LPS-induced endothelial dysfunction and apoptosis by inhibiting TLR4 and BMP4 signaling independently.

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Section: Methodsmentioning

confidence: 99%

Paeonol Attenuates LPS-Induced Endothelial Dysfunction and Apoptosis by Inhibiting BMP4 and TLR4 Signaling Simultaneously but Independently

Choy

Lau

Murugan

et al. 2017

J Pharmacol Exp Ther

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“…Blocking microglial activation by minocycline also protects the nigrostriatal dopaminergic pathway against MPTP model, suggesting that microglial activation plays a crucial role in the pathogenesis of PD ( 95 ). The treatment with paeonol decreased MPTP/p-induced oxidative stress and neuroinflammation through the increase of the brain-derived neurotrophic factor (BDNF), one of the most critical NFs in the physiology of CNS ( 96 ).…”

Section: Inflammation In Pd: Cause or Consequence Of The Disease?mentioning

confidence: 99%

Outside in: Unraveling the Role of Neuroinflammation in the Progression of Parkinson's Disease

et al. 2018

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Neuroinflammation is one of the most important processes involved in the pathogenesis of Parkinson's disease (PD). The current concept of neuroinflammation comprises an inflammation process, which occurs in the central nervous system due to molecules released from brain-resident and/or blood-derived immune cells. Furthermore, the evidence of the contribution of systemic delivered molecules to the disease pathogenesis, such as the gut microbiota composition, has been increasing during the last years. Under physiological conditions, microglia and astrocytes support the well-being and well-function of the brain through diverse functions, including neurotrophic factor secretion in both intact and injured brain. On the other hand, genes that cause PD are expressed in astrocytes and microglia, shifting their neuroprotective role to a pathogenic one, contributing to disease onset and progression. In addition, growth factors are a subset of molecules that promote cellular survival, differentiation and maturation, which are critical signaling factors promoting the communication between cells, including neurons and blood-derived immune cells. We summarize the potential targeting of astrocytes and microglia and the systemic contribution of the gut microbiota in neuroinflammation process archived in PD.

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“…Cordycepin, resveratrol, hesperetin rendered up-regulation of the level and activity of antioxidants such as, SOD, GPx, CAT, GSH in 6-OHDA induced PD models ( Khan et al, 2010 ; Kiasalari et al, 2016 ; Olatunji et al, 2016 ). Treatment with paeonol improved the MPTP-induced the oxidative stress, as determined by enhancing the activity levels of SOD, CAT, and GSH in the mouse PD model ( Shi et al, 2016 ). Gastrodin, the major active component in the Gastrodia elata , has been demonstrated to have many pharmacological effects, such as antioxidative and neuroprotective properties.…”

Section: Natural Anti-oxidant Molecules and Their Applications In Pd mentioning

confidence: 99%

Natural Molecules From Chinese Herbs Protecting Against Parkinson’s Disease via Anti-oxidative Stress

Ding

Xin

Zhang

et al. 2018

Front. Aging Neurosci.

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Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s disease, affecting about 7–10 million patients worldwide. The major pathological features of PD include loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) of the midbrain and the presence of α-synuclein-enriched Lewy bodies. Although the mechanism underlying PD pathogenesis remains to be elucidated, oxidative stress induced by the overproduction of reactive oxygen species (ROS) is widely accepted to be a key pathogenic factors. ROS cause oxidative damage to proteins, lipids, and DNA, which subsequently lead to neurodegeneration. Great efforts have been made to slow or stop the progress of PD. Unfortunately there is no effective cure for PD till now. Compounds with good antioxidant activity represent the promising candidates for therapeutics of PD. Some natural molecules from Chinese herbs are found to have good antioxidant activity. Both in vitro and in vivo studies demonstrate that these natural molecules could mitigate the oxidative stress and rescue the neuronal cell death in PD models. In present review, we summarized the reported natural molecules that displayed protective effects in PD. We also addressed the possible signal pathway through which natural molecules achieved their antioxidative effects and mitigate PD phenotypes. Hopefully it will pave the way to better recognize and utilize Chinese herbs for the treatment of PD.

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Therapeutic effects of paeonol on methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid-induced Parkinson's disease in mice

Cited by 49 publications

References 54 publications

Paeonol Attenuates LPS-Induced Endothelial Dysfunction and Apoptosis by Inhibiting BMP4 and TLR4 Signaling Simultaneously but Independently

Paeonol Attenuates LPS-Induced Endothelial Dysfunction and Apoptosis by Inhibiting BMP4 and TLR4 Signaling Simultaneously but Independently

Outside in: Unraveling the Role of Neuroinflammation in the Progression of Parkinson's Disease

Natural Molecules From Chinese Herbs Protecting Against Parkinson’s Disease via Anti-oxidative Stress

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