Nrf2/HO-1 mediates neuroprotective effects of pramipexole by attenuating oxidative damage and mitochondrial perturbation after traumatic brain injury

Salman, Mohammad; Tabassum, Heena; Parvez, Suhel

doi:10.1242/dmm.045021

Cited by 24 publications

(15 citation statements)

References 51 publications

(70 reference statements)

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“…The results are similar to other studies that proved stimulation of the NRF2 pathway via oxidative stress after TBI [92]. Not only NRF2 but the expression of the HOMX1 gene is also upregulated in this study as observed by Salman et al [93]. Saffron treatment enhanced the upregulation of NRF2, and HMOX1 to control the generated oxidative stress.…”

Section: Plos Onesupporting

confidence: 92%

Saffron extract attenuates neuroinflammation in rmTBI mouse model by suppressing NLRP3 inflammasome activation via SIRT1

et al. 2021

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Traumatic brain injury (TBI) remains a major cause of morbidity and disability worldwide and a healthcare burden. TBI is an important risk factor for neurodegenerative diseases hallmarked by exacerbated neuroinflammation. Neuroinflammation in the cerebral cortex plays a critical role in secondary injury progression following TBI. The NOD-like receptors (NLR) family pyrin domain containing 3 (NLRP3) inflammasome is a key player in initiating the inflammatory response in various central nervous system disorders entailing TBI. This current study aims to investigate the role of NLRP3 in repetitive mild traumatic brain injury (rmTBI) and identify the potential neuroprotective effect of saffron extract in regulating the NLRP3 inflammasome. 24 hours following the final injury, rmTBI causes an upregulation in mRNA levels of NLRP3, caspase-1, the apoptosis-associated speck-like protein containing a CARD (ASC), nuclear factor kappa B (NF-κB), interleukin-1Beta (IL-1β), interleukin 18 (IL-18), nuclear factor erythroid 2–related factor 2 (NRF2) and heme oxygenase 1 (HMOX1). Protein levels of NLRP3, sirtuin 1 (SIRT1), glial fibrillary acidic protein (GFAP), ionized calcium-binding adaptor molecule 1 (Iba1), and neuronal nuclei (Neu N) also increased after rmTBI. Administration of saffron alleviated the degree of TBI, as evidenced by reducing the neuronal damage, astrocyte, and microglial activation. Pretreatment with saffron inhibited the activation of NLRP3, caspase-1, and ASC concurrent to reduced production of the inflammatory cytokines IL-1β and IL-18. Additionally, saffron extract enhanced SIRT1 expression, NRF2, and HMOX1 upregulation. These results suggest that NLRP3 inflammasome activation and the subsequent inflammatory response in the mice cortex are involved in the process of rmTBI. Saffron blocked the inflammatory response and relieved TBI by activating detoxifying genes and inhibiting NLRP3 activation. The effect of saffron on the NLRP3 inflammasome may be SIRT1 and NF-κB dependent in the rmTBI model. Thus, brain injury biomarkers will help in identifying a potential therapeutic target in treating TBI-induced neurodegenerative diseases.

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Section: Plos Onesupporting

confidence: 92%

Saffron extract attenuates neuroinflammation in rmTBI mouse model by suppressing NLRP3 inflammasome activation via SIRT1

et al. 2021

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“…There have been some drugs or methods used to alleviate TBI-related neurological disorders by targeting Nrf2 and HO-1. For example, the D2-like receptor agonist pramipexole activates the Nrf2/HO-1 signaling pathway to serve a neuroprotective effect following TBI ( 9 ). The behavioral changes and reduction of oxidative stress in Wistar rats treated with tannin following TBI were attributed to the activation of PGC-1α/Nrf-2/HO-1 signaling pathway ( 54 ).…”

Section: Discussionmentioning

confidence: 99%

“…Combined antioxidant therapy to inhibit NOX 2 and activate Nrf2 decreases secondary brain damage and improves functional recovery following TBI ( 8 ). The use of pramipexole (D2-like receptor agonist) to activate the transcription process of Nrf2 and its downstream detoxification enzyme heme oxygenase-1 (HO-1) has a significant neuroprotective effect following TBI ( 9 ). Therefore, it is important to determine if compounds with antioxidant properties, such as wogonin, a flavonoid compound extracted from the plant Scutellaria baicalensis Georgi and used in traditional Chinese medicine, are effective treatments for reducing secondary TBI injury.…”

Section: Introductionmentioning

confidence: 99%

Protective role of wogonin following traumatic brain injury by reducing oxidative stress and apoptosis via the PI3K/Nrf2/HO‑1 pathway

Feng

Ju²,

Yan

et al. 2022

Int J Mol Med

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Traumatic brain injury (TBI) is usually caused by accidental injuries and traffic accidents, with a very high mortality rate. Treatment and management following TBI are essential to reduce patient injury and help improve long-term prognosis. Wogonin is a flavonoid compound with an antioxidant effect extracted from Scutellaria baicalensis Georgi. However, the function and mechanism of wogonin in protecting brain injury remain to be elucidated. The present study established a TBI model of Sprague-dawley rats and treated them with wogonin following trauma. The results showed that wogonin treatment significantly reduced neurobehavioral disorders, brain edema and hippocampal neuron damage caused by TBI. It was found that in TBI rats, administration of wogonin increased the levels of antioxidant factors glutathione, superoxide dismutase and catalase in the CA1 region of the hippocampus and significantly inhibited the production of malondialdehyde and reactive oxygen species. western blotting data showed that wogonin exerted antioxidant activity by downregulating the level of NOX 2 protein. In inhibiting cell apoptosis, wogonin upregulated the expression of Bcl-2 protein in the hippocampal cA1 region of TBI rats and inhibited caspase-3 and Bax proteins. Additionally, wogonin inhibited the progression of injury following TBI through the PI3K/Akt/nuclear factor-erythroid factor 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway. Wogonin increased the expression of phosphorylated Akt, Nrf2 and HO-1 in the hippocampus of TBI rats. Following the administration of PI3K inhibitor LY294002, the upregulation of these proteins by wogonin was partly reversed. In addition, LY294002 partially reversed the regulation of wogonin on NOX 2 , caspase-3, Bax and Bcl-2 proteins. Therefore, wogonin exerts antioxidant and anti-apoptotic properties to prevent hippocampal damage following TBI, which is accomplished through the PI3K/Akt/Nrf2/HO-1 pathway.

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“…Считается, что потеря митохондриальной функции из-за ишемии в виде окислительного стресса и активации факторов апоптоза играет решаю щую роль в развитии вторичного повреждения и последующей гибели нейронов головного мозга. Неоднократно обсуждалось, что АДР D 2 / D 3 -рецепторов способствуют нейропротекции при БП именно за счет механизмов стабилизации работы митохондрий, уменьшения количества свободных радикалов и регуляции апоптоза [36]. Применение данных препаратов в острый период повреждения клеток мозга при инфаркте может влиять как на формирование очага повреждения, так и на клинический исход инсульта.…”

Section: нейропротекция при использовании агонистов дофаминовых рецеп...unclassified

Dopamine receptor agonists: standard and non-standard applications in medicine

2022

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Dopamine receptor agonists (DRA) are a class of therapeutic drugs able to directly stimulate dopaminergic receptors facilitating a stronger effect of the endogenous dopamine, which is widely used in treatment of diseases that are accompanied with dopaminergic neurotransmission deficiency. A classical hypodopaminergic condition is Parkinson’s disease and DRA are traditionally associated with it. However, even the first DRA, Bromocriptine, widely adopted in PD treatment, was initially registered as a medication for treatment of prolactinaemia and associated pituitary adenomas and is still widely used in gynecology and endocrinology. In several countries DRA are used in treatment of diabetes, eating disorders, and addictions. Dopamine is the cardinal neurotransmitter of the emotional control and the main neurotransmitter of the reward system, and that defines the interest for researching the dopaminergic agents in treatment of primarily mental illnesses, as well as correction of secondary affective disorders. The experimental effectiveness of ADR in slowing down the rate of progression of the neurodegenerative process in severe incurable diseases, as well as potential neuroprotection in cerebrovascular insufficiency, will allow in the future to determine the criteria for the use of ADR in these non-standard situations, which may even lead to a change in clinical recommendations for the treatment of individual nosologies. Presented in this article are both traditional uses of DRA and an overview of non-standard applications of this class of medications with a discussion of recent studies. In the future, the likelihood of a rethinking of ADRs as a class of only antiparkinsonian drugs, with the expansion of their therapeutic indications.

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Nrf2/HO-1 mediates neuroprotective effects of pramipexole by attenuating oxidative damage and mitochondrial perturbation after traumatic brain injury

Cited by 24 publications

References 51 publications

Saffron extract attenuates neuroinflammation in rmTBI mouse model by suppressing NLRP3 inflammasome activation via SIRT1

Saffron extract attenuates neuroinflammation in rmTBI mouse model by suppressing NLRP3 inflammasome activation via SIRT1

Protective role of wogonin following traumatic brain injury by reducing oxidative stress and apoptosis via the PI3K/Nrf2/HO‑1 pathway

Dopamine receptor agonists: standard and non-standard applications in medicine

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