Ellagic acid activates the Keap1-Nrf2-ARE signaling pathway in improving Parkinson’s disease: A review

Wang, Qianhui; Botchway, Benson O. A.; Zhang, Yong; Liu, Xuehong

doi:10.1016/j.biopha.2022.113848

Cited by 17 publications

(10 citation statements)

References 136 publications

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“…The activation of Nrf2 mainly includes two pathways. The first classical activation pathway of Nrf2 is caused by OS ( 25 ). Specifically, Keap1 binds to Nrf2 in the cytoplasm and sequesters Nrf2 in an inactive state.…”

Section: Structure and Function Of Nrf2mentioning

confidence: 99%

Nrf2 signaling pathway: current status and potential therapeutic targetable role in human cancers

Lin,

Wu,

et al. 2023

Front. Oncol.

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Cancer is a borderless global health challenge that continues to threaten human health. Studies have found that oxidative stress (OS) is often associated with the etiology of many diseases, especially the aging process and cancer. Involved in the OS reaction as a key transcription factor, Nrf2 is a pivotal regulator of cellular redox state and detoxification. Nrf2 can prevent oxidative damage by regulating gene expression with antioxidant response elements (ARE) to promote the antioxidant response process. OS is generated with an imbalance in the redox state and promotes the accumulation of mutations and genome instability, thus associated with the establishment and development of different cancers. Nrf2 activation regulates a plethora of processes inducing cellular proliferation, differentiation and death, and is strongly associated with OS-mediated cancer. What’s more, Nrf2 activation is also involved in anti-inflammatory effects and metabolic disorders, neurodegenerative diseases, and multidrug resistance. Nrf2 is highly expressed in multiple human body parts of digestive system, respiratory system, reproductive system and nervous system. In oncology research, Nrf2 has emerged as a promising therapeutic target. Therefore, certain natural compounds and drugs can exert anti-cancer effects through the Nrf2 signaling pathway, and blocking the Nrf2 signaling pathway can reduce some types of tumor recurrence rates and increase sensitivity to chemotherapy. However, Nrf2’s dual role and controversial impact in cancer are inevitable consideration factors when treating Nrf2 as a therapeutic target. In this review, we summarized the current state of biological characteristics of Nrf2 and its dual role and development mechanism in different tumor cells, discussed Keap1/Nrf2/ARE signaling pathway and its downstream genes, elaborated the expression of related signaling pathways such as AMPK/mTOR and NF-κB. Besides, the main mechanism of Nrf2 as a cancer therapeutic target and the therapeutic strategies using Nrf2 inhibitors or activators, as well as the possible positive and negative effects of Nrf2 activation were also reviewed. It can be concluded that Nrf2 is related to OS and serves as an important factor in cancer formation and development, thus provides a basis for targeted therapy in human cancers.

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Section: Structure and Function Of Nrf2mentioning

confidence: 99%

Nrf2 signaling pathway: current status and potential therapeutic targetable role in human cancers

Lin,

Wu,

et al. 2023

Front. Oncol.

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“…EA has been demonstrated to have anticholinesterase and antioxidant activities in in vitro experiments. EA's ability to protect neurons has been demonstrated in a number of experimental models [ 18 ]. Additionally, EA can improve cholinergic transmission, which contributes to its neuroprotective properties, and reduce cognitive disruption following scopolamine injection, prevent cognitive deficits brought on by traumatic brain injury, and recover memory loss in a 6-hydroxydopamine-induced PD model in a rat model, where A-25-35 was injected intra hippocampally [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

Anti oxidative/neuro-inflammation properties of Withania somnifera root extract on rotenone induced stress in rat brain

Krishnan

2023

Bioinformation

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Parkinson's disease (PD) is a neurological condition that worsens with age (i.e., 1% of people over 65) with no permanent cure. Hence, finding a disease-modifying agent with fewer undesirable side effects is urgently needed. Parkinson's disease (PD) pathology results in the degeneration of dopaminergic (DAergic) neurons by accumulating lewy bodies, alpha-synuclein (-syn), lowering anti-oxidants, increasing neuronal inflammation, and altering neuron shape. A well-researched natural substance called withania somnifera (WS) has a potent anti-oxidative, anti-inflammatory, and anti-neurodegenerative impact. WS, sometimes called as Indian Ginseng, is a subtropical undershrub of the Solanaceae family together with Ashwagandha. In the current work, EWSR's anti-inflammatory and neuroprotective efficacy was assessed in relation to rotenone-induced oxidative stress (i.e., LPO, CAT, and SOD & GSH), microglial activation, and neurodegeneration in the rotenone rat PD model. In ROT-induced brains, EWSR therapy resulted in a considerable decrease in LPO and increased levels of the antioxidants SOD, CAT, and GSH. Furthermore, our research showed that the intraperitoneal treatment of EWSR (40 mg/kg) in rotenone-induced rats reduced microglial activation and neuron loss in the substantia nigra (SN) and hippocampus caused by rotenone-induced neurotoxicity. Based on the observations, EWSR can be considered as an excellent source for neuroprotection, due to its significant anti-oxidative, anti-inflammatory, anti-neurodegenerative and anti-microglial properties when administered individually and in combination with known anti-inflammatory compounds (Doxycycline and Ellagic acids). But, further research is required before replacing the known neuroprotective treatments with phytochemical treatments.

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“…In fruits and nuts such as grapes, strawberries, raspberries, pomegranates, and walnuts, ellagic acid (EA) is a polyphenol and a naturally occurring dimeric derivative of gallic acid, can be discovered [23][24][25][26][27] . This polyphenol functions as an antiinflammatory and antioxidant in mammalian cells 25,26 .…”

Section: Introductionmentioning

confidence: 99%

“…In-vitro studies have shown EA to have anticholinesterase and antioxidant properties. EA's neuroprotective function has been documented in a variety of experimental models 24 . Additionally, EA can lessen cognitive disruption after scopolamine injection, prevent cognitive deficits brought on by traumatic brain damage, and restore memory loss in a 6-hydroxydopamine-induced PD model.…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, EA can lessen cognitive disruption after scopolamine injection, prevent cognitive deficits brought on by traumatic brain damage, and restore memory loss in a 6-hydroxydopamine-induced PD model. Neuroprotective potential of EA is by improving cholinergic transmission in an intrahippocampal Aβ-25-35-injected rat model of AD [22][23][24][25][26][27][28] .…”

Section: Introductionmentioning

confidence: 99%

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Untitled

2023

IJPSR

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Parkinson's disease (PD) is the second most prevalent type of neurodegenerative disorder and is a chronic, progressive condition. In the current investigation, we used a rotenone (ROT)-developing rat model of PD to assess the neuroprotective efficacy of ethanolic Withania somnifera root extract (EWSR) in comparison to the known neuroprotectants i.e., Doxycycline (Doxy), and ellagic acid (EA) individually and in combination (EWSR-Doxy-EA). Male Wistar rats were given ROT at a dose of 2.5 mg/kg body weight daily for 4 weeks to develop a PD invivo model. Once the PD model is confirmed, the rats were treated with individual neuroprotectants for next 5 weeks and kept under observation for next 7 days for reversal of PD. ROT administration has altered behavioural parameters (Cognitive, motor dysfunction, sniffing, grooming, raring, crossing, etc.) and neurotransmitter profile (Acetylcholine, epinephrine, nor-epinephrine, dopamine, glutamate and aspartate) in rats. The administration of neuroprotectants has ameliorated the deleterious effects of rotenone and restored cognitive and motor control by rectifying the levels of neurotransmitters which are responsible for the functions. EWSR protective efficacy was significantly better to that of the known neuroprotectants (Doxy and EA) and EWSR efficacy increased significantly when combined with the other neuroprotectants. Based on the study observations, it can be inferred that EWSR is a good neuroprotective agent and can act as a potential alternative therapeutic approach individually or in combination with known drugs in treating PD and other neurodegenerative diseases.

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Ellagic acid activates the Keap1-Nrf2-ARE signaling pathway in improving Parkinson’s disease: A review

Cited by 17 publications

References 136 publications

Nrf2 signaling pathway: current status and potential therapeutic targetable role in human cancers

Nrf2 signaling pathway: current status and potential therapeutic targetable role in human cancers

Anti oxidative/neuro-inflammation properties of Withania somnifera root extract on rotenone induced stress in rat brain

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