Pramipexole reduces inflammation in the experimental animal models of inflammation

Sadeghi, Heibatollah; Parishani, Mohammad; Touri, Mehdi Akbartabar; Ghavamzadeh, Mehdi; Barmak, Mehrzad Jafari; Zarezade, Vahid; Delaviz, Hamdollah; Sadeghi, Hossein

doi:10.1080/08923973.2017.1284230

Cited by 31 publications

(14 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Ear edema caused by croton oil or its irritant principle 12-O-tetradecanoylphorbol-13-acetate (TPA) has been extensively used to assess the anti-inflammatory activity of steroidal and non-steroidal anti-inflammatory drugs [132]. TPA-induced ear inflammation represents the model of skin inflammation useful for the appraisal of systemic and local anti-inflammatory compounds [135]. Topical administration of croton oil causes vasodilatation, promote vascular permeability, neutrophil influx, synthesis of eicosanoids, and liberation of serotonin and histamine [130].…”

Section: Anti-inflammatory Drug Development From Natural Products:mentioning

confidence: 99%

Animal Models of Inflammation for Screening of Anti-inflammatory Drugs: Implications for the Discovery and Development of Phytopharmaceuticals

Patil

Mahajan

Unger³

et al. 2019

IJMS

261

175

View full text Add to dashboard Cite

Inflammation is one of the common events in the majority of acute as well as chronic debilitating diseases and represent a chief cause of morbidity in today’s era of modern lifestyle. If unchecked, inflammation leads to development of rheumatoid arthritis, diabetes, cancer, Alzheimer’s disease, and atherosclerosis along with pulmonary, autoimmune and cardiovascular diseases. Inflammation involves a complex network of many mediators, a variety of cells, and execution of multiple pathways. Current therapy for inflammatory diseases is limited to the steroidal and non-steroidal anti-inflammatory agents. The chronic use of these drugs is reported to cause severe adverse effects like gastrointestinal, cardiovascular, and renal abnormalities. There is a massive need to explore new anti-inflammatory agents with selective action and lesser toxicity. Plants and isolated phytoconstituents are promising and interesting sources of new anti-inflammatories. However, drug development from natural sources has been linked with hurdles like the complex nature of extracts, difficulties in isolation of pure phytoconstituents, and the yield of isolated compounds in minute quantities that is insufficient for subsequent lead development. Although various in-vivo and in-vitro models for anti-inflammatory drug development are available, judicious selection of appropriate animal models is a vital step in the early phase of drug development. Systematic evaluation of phytoconstituents can facilitate the identification and development of potential anti-inflammatory leads from natural sources. The present review describes various techniques of anti-inflammatory drug screening with its advantages and limitations, elaboration on biological targets of phytoconstituents in inflammation and biomarkers for the prediction of adverse effects of anti-inflammatory drugs. The systematic approach proposed through present article for anti-inflammatory drug screening can rationalize the identification of novel phytoconstituents at the initial stage of drug screening programs.

show abstract

Section: Anti-inflammatory Drug Development From Natural Products:mentioning

confidence: 99%

Animal Models of Inflammation for Screening of Anti-inflammatory Drugs: Implications for the Discovery and Development of Phytopharmaceuticals

Patil

Mahajan

Unger³

et al. 2019

IJMS

261

175

View full text Add to dashboard Cite

show abstract

“…The US Food and Drug Administration (FDA) has approved it as a drug used for the treatment of Parkinson's disease and restless leg syndrome ( Pich and Collo, 2015 ; Benbir and Guilleminault, 2006 ). It is reported that PPX exerts neuroprotective effects by reducing oxidative damage, mitochondrial dysfunction and apoptosis, owing to its role as an inhibitor or scavenger of free radicals, and blocks mitochondrial permeability transition pores (mtPTPs) through the inhibition of depolarizing membrane currents in dysfunctional mitochondria in various models ( Inden et al, 2009 ; Sayeed et al, 2006 ; Sadeghi et al, 2017 ). PPX inhibits the early brain injury after subarachnoid hemorrhage ( Ma et al, 2016 ) and significantly reduces lipid peroxidation in a rat model of Parkinson's disease ( Zou et al, 2000 ).…”

Section: Introductionmentioning

confidence: 99%

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

Salman

Tabassum

Parvez

2020

Disease Models &Amp; Mechanisms

View full text Add to dashboard Cite

Pramipexole (PPX), a D2-like receptor agonist, is generally used in the treatment of Parkinson's disease and restless leg syndrome. Its neuroprotective effects have been shown against various neurological disorders. Recent research work has demonstrated that PPX exerts neuroprotection through mitochondria. However, the neuromodulator-related effects of PPX against traumatic brain injury (TBI) remain unexplored. The present study, therefore, investigated the mechanism of neuroprotection by PPX against oxidative stress, mitochondrial dysfunction and neuronal damage following TBI in rats. We hypothesized that the neuroprotection by PPX in TBI-subjected rats might involve activation of the Nrf2/HO-1 (also known as Nfe2l2/Hmox1) signaling pathway. PPX was injected intraperitoneally (0.25 mg/kg body weight and 1.0 mg/kg body weight) at different time intervals post-TBI. Several neurobehavioral parameters were assessed at 48 h post-TBI, and the brain was isolated for molecular and biochemical analysis. The results demonstrated that PPX treatment significantly improved the behavioral deficits, decreased the lipid peroxidation rate, increased glutathione levels and decreased 4-hydroxynonenal levels in TBI-subjected rats. PPX also increased the activities of glutathione peroxidase and superoxide dismutase enzymes. In addition, PPX treatment inhibited mitochondrial reactive oxygen species production, restored mitochondrial membrane potential and increased ATP levels after a TBI. Further, PPX treatment reduced the Bax/Bcl2 ratio and translocation of Bax to mitochondria and cytochrome-c to the cytosol. Finally, PPX treatment greatly accelerated the translocation of Nrf2 to the nucleus and upregulated HO-1 protein expression. We conclude that the neuroprotective effects of PPX are mediated by activation of the Nrf2/HO-1 signaling pathway following TBI.This article has an associated First Person interview with the first author of the paper.

show abstract

“…Dopamine D2 receptor (Drd2) has been regarded as a potential anti-inflammatory target in the therapy of NDDs [ 19 – 21 ]. Drd2 expresses both in neurons and astrocytes [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

α-Synuclein disrupts the anti-inflammatory role of Drd2 via interfering β-arrestin2-TAB1 interaction in astrocytes

Zhou

Xia

et al. 2018

J Neuroinflammation

View full text Add to dashboard Cite

Backgroundα-Synuclein (α-Syn)-induced neuroinflammation plays a crucial role in the pathogenesis of Parkinson’s disease (PD). Dopamine D2 receptor (Drd2) has been regarded as a potential anti-inflammatory target in the therapy of neurodegenerative diseases. However, the effect of astrocytic Drd2 in α-Syn-induced neuroinflammation remains unclear.MethodsThe effect of Drd2 on neuroinflammation was examined in mouse primary astrocyte in vitro and A53T transgenic mice in vivo. The inflammatory responses of astrocyte were detected using immunofluorescence, ELISA, and qRT-PCR. The details of molecular mechanism were assessed using Western blotting and protein-protein interaction assays.ResultsWe showed that the selective Drd2 agonist quinpirole suppressed inflammation in the midbrain of wild-type mice, but not in α-Syn-overexpressed mice. We also found that Drd2 agonists significantly alleviated LPS-induced inflammatory response in astrocytes, but failed to suppress α-Syn-induced inflammatory response. The anti-inflammation effect of Drd2 was dependent on β-arrestin2-mediated signaling, but not classical G protein pathway. α-Syn reduced the expression of β-arrestin2 in astrocytes. Increased the β-arrestin2 expression restored in the anti-inflammation of Drd2 in α-Syn-induced inflammation. Furthermore, we demonstrated that α-Syn disrupted the anti-inflammation of Drd2 via inhibiting the association of β-arrestin2 with transforming growth factor-beta-activated kinase 1 (TAK1)-binding protein 1 (TAB1) and promoting TAK1-TAB1 interaction in astrocytes.ConclusionsOur study illustrates that astrocytic Drd2 inhibits neuroinflammation through a β-arrestin2-dependent mechanism and provides a new strategy for treatment of PD. Our findings also reveal that α-Syn disrupts the function of β-arrestin2 and inflammatory pathways in the pathogenesis of PD.

show abstract

Pramipexole reduces inflammation in the experimental animal models of inflammation

Cited by 31 publications

References 29 publications

Animal Models of Inflammation for Screening of Anti-inflammatory Drugs: Implications for the Discovery and Development of Phytopharmaceuticals

Animal Models of Inflammation for Screening of Anti-inflammatory Drugs: Implications for the Discovery and Development of Phytopharmaceuticals

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

α-Synuclein disrupts the anti-inflammatory role of Drd2 via interfering β-arrestin2-TAB1 interaction in astrocytes

Contact Info

Product

Resources

About