scholarly journals Acetyl-L-Carnitine protects against LPS induced depression via PPAR-γ induced inhibition of NF-κB/NLRP3 pathway

2021 ◽  
Author(s):  
Amna Samin ◽  
Lina Tariq Al Kury ◽  
MUHAMMAD IMRAN KHAN ◽  
Shabir Hussain ◽  
Abdullah Alattar ◽  
...  
Keyword(s):  
Caffeic Acid ◽  
Nlrp3 Inflammasome ◽  
Caffeic Acid Phenethyl Ester ◽  
Peroxisome Proliferator ◽  
Depression And Anxiety ◽  
Sprague Dawley ◽  
Neuroprotective Effects ◽  
Pyrin Domain ◽  
Ppar Γ ◽  
Peroxisome Proliferator Activated Receptors

IntroductionMajor depressive disorder (MDD) is a debilitating human health status characterized by mood swings and high suicidal attempts. Several studies have reported the role of neuroinflammation in MMD, yet the efficacy of natural drug substances on neuroinflammation-associated depression needs to be further investigated. The present study demonstrated the neuroprotective effects of Acetyl-L- carnitine (ALC) alone or in combination with caffeic acid phenethyl ester (CAPE) on lipopolysaccharide (LPS) induced neuro-inflammation, depression, and anxiety-like behavior.Material and methodsMale Sprague Dawley (SD) rats were used to explore the relative effects of ALC and the mechanistic interplay of the peroxisome proliferator-activated receptors (PPARγ) in depression. Lipopolysaccharide (LPS) was administered to induce depression and anxiety-like symptoms such as a decreased grooming tendency, diminished locomotive activity, and increased immobility period.ResultsWe found marked neuronal alterations in the cortex and hippocampus of LPS intoxicated animals associated with higher inflammatory cytokines expression cyclooxygenase (COX2), tumor necrotic factor-alpha (TNF-α). These detrimental effects exacerbate oxidative stress as documented by a compromised antioxidant system due to high lipid peroxidase (LPO). ALC significantly reverted these changes by positively modulating the PPARγ dependent downstream antioxidant and anti-inflammatory pathways such as NOD and pyrin domain-containing protein 3 (NLRP3) linked nuclear factor kappa B (NF-κB) phosphorylation. Moreover, co-administering NF-κB inhibitor caffeic acid phenethyl ester (CAPE) with ALC also increased PPARγ expression significantly and decreased NF-ᴋB and NLRP3 inflammasome.ConclusionsThese findings indicate that ALC could be a possible depression supplement. The effects are partly mediated by inhibiting neuroinflammation and NLRP3 inflammasome coupled to PPARγ upregulations.

scholarly journals Caffeic Acid Phenethyl Ester Prevents Colitis-Associated Cancer by Inhibiting NLRP3 Inflammasome

2020 ◽  
Vol 10 ◽  
Author(s):  
Guoliang Dai ◽  
Zhitao Jiang ◽  
Bingting Sun ◽  
Chao Liu ◽  
Qinghai Meng ◽  
...  
Keyword(s):  
Caffeic Acid ◽  
Nlrp3 Inflammasome ◽  
Caffeic Acid Phenethyl Ester

scholarly journals Effects of peroxisome proliferator activated receptors (PPAR)-γ and -α agonists on cochlear protection from oxidative stress

PLoS ONE ◽  
2017 ◽  
Vol 12 (11) ◽  
pp. e0188596 ◽  
Author(s):  
Marijana Sekulic-Jablanovic ◽  
Vesna Petkovic ◽  
Matthew B. Wright ◽  
Krystsina Kucharava ◽  
Nathan Huerzeler ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Peroxisome Proliferator ◽  
Ppar Γ ◽  
Peroxisome Proliferator Activated Receptors

scholarly journals Pharmacological Blockade of PPAR Isoforms Increases Conditioned Fear Responding in the Presence of Nociceptive Tone

Molecules ◽  
2020 ◽  
Vol 25 (4) ◽  
pp. 1007 ◽  
Author(s):  
Jessica C. Gaspar ◽  
Bright N. Okine ◽  
Alvaro Llorente-Berzal ◽  
Michelle Roche ◽  
David P. Finn
Keyword(s):  
Conditioned Fear ◽  
Intraperitoneal Administration ◽  
Peroxisome Proliferator ◽  
Sprague Dawley ◽  
Intraplantar Injection ◽  
Conditioned Analgesia ◽  
Sprague Dawley Rats ◽  
Pharmacological Blockade ◽  
Peroxisome Proliferator Activated Receptors ◽  
Nociceptive Behaviour

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors with three isoforms (PPARα, PPARβ/δ, PPARγ) and can regulate pain, anxiety, and cognition. However, their role in conditioned fear and pain-fear interactions has not yet been investigated. Here, we investigated the effects of systemically administered PPAR antagonists on formalin-evoked nociceptive behaviour, fear-conditioned analgesia (FCA), and conditioned fear in the presence of nociceptive tone in rats. Twenty-three and a half hours following fear conditioning to context, male Sprague-Dawley rats received an intraplantar injection of formalin and intraperitoneal administration of vehicle, PPARα (GW6471), PPARβ/δ (GSK0660) or PPARγ (GW9662) antagonists, and 30 min later were re-exposed to the conditioning arena for 15 min. The PPAR antagonists did not alter nociceptive behaviour or fear-conditioned analgesia. The PPARα and PPARβ/δ antagonists prolonged context-induced freezing in the presence of nociceptive tone without affecting its initial expression. The PPARγ antagonist potentiated freezing over the entire trial. In conclusion, pharmacological blockade of PPARα and PPARβ/δ in the presence of formalin-evoked nociceptive tone, impaired short-term, within-trial fear-extinction in rats without affecting pain response, while blockade of PPARγ potentiated conditioned fear responding. These results suggest that endogenous signalling through these three PPAR isoforms may reduce the expression of conditioned fear in the presence of nociceptive tone.

The nuclear receptor peroxisome proliferator-activated receptor-γ promotes oligodendrocyte differentiation through mechanisms involving mitochondria and oscillatory Ca2+ waves

2013 ◽  
Vol 394 (12) ◽  
pp. 1607-1614 ◽  
Author(s):  
Antonietta Bernardo ◽  
Roberta De Simone ◽  
Chiara De Nuccio ◽  
Sergio Visentin ◽  
Luisa Minghetti
Keyword(s):  
Nuclear Receptor ◽  
Neurological Diseases ◽  
Mitochondrial Respiratory Chain ◽  
Peroxisome Proliferator ◽  
Neuroprotective Effects ◽  
Peroxisome Proliferator Activated Receptor ◽  
Environmental Signals ◽  
Ppar Γ ◽  
Mitochondrial Respiratory Chain Activity ◽  
Respiratory Chain Activity

Abstract Peroxisome proliferator-activated receptor-γ (PPAR-γ) is one of the most studied nuclear receptor since its identification as a target to treat metabolic and neurological diseases. In addition to exerting anti-inflammatory and neuroprotective effects, PPAR-γ agonists, such as the insulin-sensitizing drug pioglitazone, promote the differentiation of oligodendrocytes (OLs), the myelin-forming cells of the central nervous system (CNS). In addition, PPAR-γ agonists increase OL mitochondrial respiratory chain activity and OL’s ability to respond to environmental signals with oscillatory Ca2+ waves. Both OL maturation and oscillatory Ca2+ waves are prevented by the mitochondrial inhibitor rotenone and restored by PPAR-γ agonists, suggesting that PPAR-γ promotes myelination through mechanisms involving mitochondria.

scholarly journals Immunometabolic modulation of retinal inflammation by CD36 ligand

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Katia Mellal ◽  
Samy Omri ◽  
Mukandila Mulumba ◽  
Houda Tahiri ◽  
Carl Fortin ◽  
...  
Keyword(s):  
Mononuclear Phagocytes ◽  
Inflammasome Activation ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Peroxisome Proliferator Activated Receptor ◽  
Pyrin Domain ◽  
Ppar Γ ◽  
Injury Characteristic ◽  
And Function ◽  
Cluster Of Differentiation

Abstract In subretinal inflammation, activated mononuclear phagocytes (MP) play a key role in the progression of retinopathies. Little is known about the mechanism involved in the loss of photoreceptors leading to vision impairment. Studying retinal damage induced by photo-oxidative stress, we observed that cluster of differentiation 36 (CD36)-deficient mice featured less subretinal MP accumulation and attenuated photoreceptor degeneration. Moreover, treatment with a CD36-selective azapeptide ligand (MPE-001) reduced subretinal activated MP accumulation in wild type mice and preserved photoreceptor layers and function as assessed by electroretinography in a CD36-dependent manner. The azapeptide modulated the transcriptome of subretinal activated MP by reducing pro-inflammatory markers. In isolated MP, MPE-001 induced dissociation of the CD36-Toll-like receptor 2 (TLR2) oligomeric complex, decreasing nuclear factor-kappa B (NF-κB) and NLR family pyrin domain containing 3 (NLRP3) inflammasome activation. In addition, MPE-001 caused an aerobic metabolic shift in activated MP, involving peroxisome proliferator-activated receptor-γ (PPAR-γ) activation, which in turn mitigated inflammation. Accordingly, PPAR-γ inhibition blocked the cytoprotective effect of MPE-001 on photoreceptor apoptosis elicited by activated MP. By altering activated MP metabolism, MPE-001 decreased immune responses to alleviate subsequent inflammation-dependent neuronal injury characteristic of various vision-threatening retinal disorders.

Neuroprotective Potential of Caffeic Acid Phenethyl Ester (CAPE) in CNS Disorders: Mechanistic and Therapeutic Insights

2021 ◽  
Vol 19 ◽  
Author(s):  
Namrata Pramod Kulkarni ◽  
Bhupesh Vaidya ◽  
Acharan Narula ◽  
Shyam Sunder Sharma
Keyword(s):  
Caffeic Acid ◽  
Neurological Disorders ◽  
Therapeutic Potential ◽  
Caffeic Acid Phenethyl Ester ◽  
Depression And Anxiety ◽  
Age Related ◽  
Anti Cancer ◽  
Therapeutic Molecules ◽  
Conifer Trees ◽  
Lateral Sclerosis

: Neurological disorders like Alzheimer’s disease (AD), Parkinson’s disease (PD), stroke, amyotrophic lateral sclerosis, Huntington’s disease (HD), epilepsy, traumatic brain injury (TBI), depression and anxiety are responsible for thousands of deaths worldwide every year. With the increase in life expectancy, there has been a rise in the prevalence of these disorders. Age is one of the major risk factors for these neurological disorders and with the aged population is set to rise to 1.25 billion by 2050. There is a growing concern to look for new therapeutic molecules to treat age-related diseases. Caffeic acid phenethyl ester (CAPE) is a molecule obtained from a number of botanical sources such as the bark of conifer trees as well as propolis which is extracted from beehives. Though CAPE remains relatively unexplored in human trials, it possesses antioxidant, anti-inflammatory, antimitogenic and anti-cancer activities as shown by preclinical studies. Apart from this, it also exhibits tremendous potential for the treatment of neurological disorders through modulation of multiple molecular pathways and attenuation of behavioural deficits. In the present article, we have reviewed the therapeutic potential of CAPE and its mechanisms in the treatment of neurological disorders.

scholarly journals Telmisartan prevents the glitazone-induced weight gain without interfering with its insulin-sensitizing properties

2007 ◽  
Vol 293 (1) ◽  
pp. E91-E95 ◽  
Author(s):  
Anne Zanchi ◽  
Abdul G. Dulloo ◽  
Christine Perregaux ◽  
Jean-Pierre Montani ◽  
Michel Burnier
Keyword(s):  
Weight Gain ◽  
Fat Mass ◽  
Zucker Rats ◽  
Peroxisome Proliferator ◽  
Concomitant Treatment ◽  
Sprague Dawley ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Sprague Dawley Rats

Glitazones are peroxisome proliferator-activated receptor (PPAR)-γ agonists with powerful insulin-sensitizing properties. They promote the development of metabolically active adipocytes that can lead to a substantial gain in fat mass. Telmisartan is an ANG II type 1 receptor antagonist with partial PPAR-γ agonistic properties. Recently, telmisartan has been reported to prevent weight gain and improve insulin sensitivity in diet-induced obese rodents. The goal of this study was to examine the influence of telmisartan on pioglitazone-induced weight gain and insulin-sensitizing properties in the following two models of insulin resistance: a nongenetic model (high-fat-fed Sprague Dawley rats) and the genetically obese fa/ fa Zucker rat. After a 4-wk treatment, the pioglitazone-induced increase in fat mass was modest in the Sprague Dawley rats and severe in the Zucker rats. In both models, these effects were substantially decreased by concomitant treatment with telmisartan. The effects of telmisartan on body weight and fat mass in the Zucker rats were abolished by pair feeding, suggesting that it is the result of a decrease in food intake. Telmisartan did not interfere with the insulin-sensitizing properties of pioglitazone. This study demonstrates that telmisartan attenuates the glitazone-induced increase in fat mass without interfering with its insulin-sensitizing properties.

scholarly journals Expression Pattern of Peroxisome Proliferator-Activated Receptors in Rat Hippocampus following Cerebral Ischemia and Reperfusion Injury

PPAR Research ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Hong Wang ◽  
Rong Jiang ◽  
Qin He ◽  
Yunmei Zhang ◽  
Yanli Zhang ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Rat Hippocampus ◽  
Global Cerebral Ischemia ◽  
Peroxisome Proliferator ◽  
Ischemia And Reperfusion ◽  
Sprague Dawley ◽  
Ischemia And Reperfusion Injury ◽  
Protein Levels ◽  
Cerebral Ischemia And Reperfusion ◽  
Peroxisome Proliferator Activated Receptors

The present study was designed to investigate the pattern of time-dependent expression of peroxisome proliferator-activated receptors (PPARα,β, andγ) after global cerebral ischemia and reperfusion (I/R) damage in the rat hippocampus. Male Sprague Dawley (SD) rats were subjected to global cerebral I/R. The rat hippocampi were isolated to detect the expression of PPARs mRNA and protein levels at 30 min–30 d after I/R by RT-PCR and Western blot analysis, respectively. The expression levels of PPARs mRNA and protein in the rat hippocampus significantly increased and peaked at 24 h for PPARαandγ(at 48 h for PPARβ) after I/R, then gradually decreased, and finally approached control levels on d 30. The present results suggest that global cerebral I/R can cause obvious increases of hippocampal PPARs mRNA and protein expression within 15 d after I/R. These findings may help to guide the experimental and clinical therapeutic use of PPARs agonists against brain injury.

Peroxisome proliferator-activated receptors and cardiovascular remodeling

2005 ◽  
Vol 288 (3) ◽  
pp. H1037-H1043 ◽  
Author(s):  
Ernesto L. Schiffrin
Keyword(s):  
Cardiovascular Disease ◽  
Target Genes ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Fat Cell ◽  
Ppar Γ ◽  
Peroxisome Proliferator Activated Receptors ◽  
Prevention Of Cardiovascular Disease

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that heterodimerize with the retinoid X receptor and then modulate the function of many target genes. Three PPARs are known: α, β/δ, and γ. The better known are PPAR-α and PPAR-γ, which may be activated by different synthetic agonists, although the endogenous ligands are unknown. PPAR-α is involved in fatty acid oxidation and expressed in the liver, kidney, and skeletal muscle, whereas PPAR-γ is involved in fat cell differentiation, lipid storage, and insulin sensitivity. However, both have been shown to be present in variable amounts in cardiovascular tissues, including endothelium, smooth muscle cells, macrophages, and the heart. The activators of PPAR-α (fibrates) and PPAR-γ (thiazolidinediones or glitazones) antagonized the actions of angiotensin II in vivo and in vitro and exerted cardiovascular antioxidant and anti-inflammatory effects. PPAR activators lowered blood pressure, induced favorable effects on the heart, and corrected vascular structure and endothelial dysfunction in several rodent models of hypertension. Activators of PPARs may become therapeutic agents useful in the prevention of cardiovascular disease beyond their effects on carbohydrate and lipid metabolism. Some side effects, such as weight gain, as well as documented aggravation of advanced heart failure through fluid retention by glitazones, may, however, limit their therapeutic application in prevention of cardiovascular disease.

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