The Neuroprotective Role of Polydatin: Neuropharmacological Mechanisms, Molecular Targets, Therapeutic Potentials, and Clinical Perspective

Neurodegenerative diseases (NDDs) are one of the leading causes of death and disability in humans. From a mechanistic perspective, the complexity of pathophysiological mechanisms contributes to NDDs. Therefore, there is an urgency to provide novel multi-target agents towards the simultaneous modulation of dysregulated pathways against NDDs. Besides, their lack of effectiveness and associated side effects have contributed to the lack of conventional therapies as suitable therapeutic agents. Prevailing reports have introduced plant secondary metabolites as promising multi-target agents in combating NDDs. Polydatin is a natural phenolic compound, employing potential mechanisms in fighting NDDs. It is considered an auspicious phytochemical in modulating neuroinflammatory/apoptotic/autophagy/oxidative stress signaling mediators such as nuclear factor-κB (NF-κB), NF-E2–related factor 2 (Nrf2)/antioxidant response elements (ARE), matrix metalloproteinase (MMPs), interleukins (ILs), phosphoinositide 3-kinases (PI3K)/protein kinase B (Akt), and the extracellular regulated kinase (ERK)/mitogen-activated protein kinase (MAPK). Accordingly, polydatin potentially counteracts Alzheimer’s disease, cognition/memory dysfunction, Parkinson’s disease, brain/spinal cord injuries, ischemic stroke, and miscellaneous neuronal dysfunctionalities. The present study provides all of the neuroprotective mechanisms of polydatin in various NDDs. Additionally, the novel delivery systems of polydatin are provided regarding increasing its safety, solubility, bioavailability, and efficacy, as well as developing a long-lasting therapeutic concentration of polydatin in the central nervous system, possessing fewer side effects.

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Artemisia asiatica Nakai Attenuates the Expression of Proinflammatory Mediators in Stimulated Macrophages Through Modulation of Nuclear Factor-κB and Mitogen-Activated Protein Kinase Pathways

Journal of Medicinal Food ◽

10.1089/jmf.2014.3344 ◽

2015 ◽

Vol 18 (8) ◽

pp. 921-928 ◽

Cited By ~ 1

Author(s):

Eun-Kyung Kim ◽

Yujiao Tang ◽

Kwang-Suk Cha ◽

Heeri Choi ◽

Chun Bok Lee ◽

...

Keyword(s):

Protein Kinase ◽

Nuclear Factor Κb ◽

Mitogen Activated Protein Kinase ◽

Nuclear Factor ◽

Proinflammatory Mediators ◽

Mitogen Activated Protein ◽

Artemisia Asiatica

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Gulati AP, Yang Y-M, Harter D, Mukhopadhyay A, Aggarwal BA, Benzil DL, Whysner J, Albino AP, Murali R, Jhanwar-Uniyal M. Mutant human tumor suppressor p53 modulates the activation of mitogen-activated protein kinase and nuclear factor-κB, but not c-Jun N-terminal kinase and activated protein-1. Mol Carcinog 2005;45:26–37.

Molecular Carcinogenesis ◽

10.1002/mc.20251 ◽

2006 ◽

Vol 45 (7) ◽

pp. 549-549

Keyword(s):

Protein Kinase ◽

Tumor Suppressor ◽

Human Tumor ◽

Nuclear Factor Κb ◽

Mitogen Activated Protein Kinase ◽

Nuclear Factor ◽

Tumor Suppressor P53 ◽

Mitogen Activated Protein

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Phosphothreonine Lyase Promotes p65 Degradation in a Mitogen-Activated Protein Kinase/Mitogen- and Stress-Activated Protein Kinase 1-Dependent Manner

Infection and Immunity ◽

10.1128/iai.00508-18 ◽

2018 ◽

Vol 87 (1) ◽

Cited By ~ 1

Author(s):

Mingyu Hou ◽

Wenhui Wang ◽

Feizi Hu ◽

Yuanxing Zhang ◽

Dahai Yang ◽

...

Keyword(s):

Protein Kinase ◽

Pathogenic Bacteria ◽

Critical Role ◽

Nuclear Factor Κb ◽

Mapk Signaling ◽

Mitogen Activated Protein Kinase ◽

Dependent Manner ◽

Content Type ◽

Catalytic Active Site ◽

Mitogen Activated Protein

ABSTRACT Bacterial phosphothreonine lyases have been identified to be type III secretion system (T3SS) effectors that irreversibly dephosphorylate host mitogen-activated protein kinase (MAPK) signaling to promote infection. However, the effects of phosphothreonine lyase on nuclear factor κB (NF-κB) signaling remain largely unknown. In this study, we detected significant phosphothreonine lyase-dependent p65 degradation during Edwardsiella piscicida infection in macrophages, and this degradative effect was blocked by the protease inhibitor MG132. Further analysis revealed that phosphothreonine lyase promotes the dephosphorylation and ubiquitination of p65 by inhibiting the phosphorylation of mitogen- and stress-activated protein kinase-1 (MSK1) and by inhibiting the phosphorylation of extracellular signal-related kinase 1/2 (ERK1/2), p38α, and c-Jun N-terminal kinase (JNK). Moreover, we revealed that the catalytic active site of phosphothreonine lyase plays a critical role in regulating the MAPK-MSK1-p65 signaling axis. Collectively, the mechanism described here expands our understanding of the pathogenic effector in not only regulating MAPK signaling but also regulating p65. These findings uncover a new mechanism by which pathogenic bacteria overcome host innate immunity to promote pathogenesis.

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