Diacerein decreases TNF-α and IL-1β levels in peritoneal fluid and prevents Baker’s yeast-induced fever in young rats

Pasin, Juliana Saibt Martins; Ferreira, Ana Paula Oliveira; Saraiva, André Lopes; Ratzlaff, Viviane; Andrighetto, Rosália; Tomazetti, Jorgete; Ávila, Daiana Silva; Alves, Sydney Hartz; Rubin, Maribel Antonello; Ferreira, Juliano; Santos, Adair R.S.; Mello, Carlos Fernando

doi:10.1007/s00011-009-0085-8

Cited by 32 publications

(32 citation statements)

References 36 publications

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“…Rhein is converted after medication of diacerein and serves as active metabolite to suppress inflammatory reactions in the afflicted regions. Diacerein effectively suppresses the fever caused by Baker's yeast and attenuates IL-1β and TNF-α levels in peritoneal fluid [9]. Argirein is a supermolecule derived from chemical modification of rhein by combining with L-arginine through hydrogen bond (Fig.1a).…”

Section: Introductionmentioning

confidence: 99%

ER Stress, P66shc, and P-Akt/Akt Mediate Adjuvant-Induced Inflammation, Which Is Blunted by Argirein, a Supermolecule and Rhein in Rats

et al. 2011

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We investigated the anti-inflammatory activities of argirein and rhein on inflammatory edema in rat paw which was caused by complete adjuvant, compared with ibuprofen. We hypothesized that the adjuvant-induced inflammation is attributed to upregulation of activating transcript factor 6 (ATF6; a chaperone for endoplasmic reticulum (ER) stress), p66Shc (an adaptive protein modulating oxidative stress), and NADPH oxidase subunits p22phox and gp91phox in the inflamed tissues. Biomarkers were measured in the rat paw in association with monitoring swellings. The primary inflammatory edema of the injected paw occurred rapidly and sustained over a couple of days, and the secondary inflammation developed 2 weeks later. The inflammatory edema was accompanied by upregulation of cytokines including ATF6, p66Shc, p22phox, gp91phox, and MMP-2 and an increase in ratio of p-Akt/Akt in the afflicted paw. These were suppressed by either argirein and rhein or ibuprofen. These findings indicate that ER stress, upregulated p66Shc, and phosphorylated Akt are actively implicated in the inflammatory zone caused by adjuvant injection. These biomarkers were causal factors responsible for inflammation of the afflicted paw and were suppressed by a supermolecule argirein and rhein, and the anti-inflammatory activities of the two compounds were comparable to that of ibuprofen.

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Section: Introductionmentioning

confidence: 99%

ER Stress, P66shc, and P-Akt/Akt Mediate Adjuvant-Induced Inflammation, Which Is Blunted by Argirein, a Supermolecule and Rhein in Rats

et al. 2011

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“…Pasin et al found that diacerein inhibits the release of TNF-α and IL-1β and reduced their levels in the peritoneal fluid of rats. 9 Moore et al reported that the chondroprotective effects of diacerein is mainly explained by a reduction in the concentrations of pro-inflammatory cytokine especially TNF-α and IL-6. 22 Moreover, in accordance with our results, Tobar et al reported that diacerein improves insulin sensitivity, reduces macrophage infiltration and cytokine production in the muscle and liver in an animal model of obesity and type 2 diabetes.…”

Section: Discussionmentioning

confidence: 99%

“…8 Diacerein is an anthraquinone compound, of which the active metabolite is rhein, with anti-inflammatory properties that inhibit the synthesis and activity of proinflammatory cytokines, such as TNF-α, IL-1β and IL-6. 9 Diacerein is a compound with a long history but whose effects are still not fully understood. Recently, knowledge about diacerein, showed that this drug improves insulin sensitivity, through the reversal of chronic subclinical inflammation.…”

Section: Introductionmentioning

confidence: 99%

Beneficial effects of diacerein on adipokines and pro-inflammatory cytokines involved in diet-induced nonalcoholic steatohepatitis in rats

Allah

2017

Int J Basic Clin Pharmacol

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Background: Non-alcoholic steatohepatitis (NASH) is considered as a progressive liver disease, so effective therapies are needed to ameliorate hepatic steatosis, inflammation and fibrosis, and to prevent the progression to cirrhosis and hepatocellular carcinoma. Diacerein is an anti-inflammatory drug that inhibits the synthesis and activity of pro-inflammatory cytokines. The present study was designed to investigate the effect of diacerein on pro-inflammatory cytokines as well as adipokines involved in diet-induced NASH rat model.Methods: Thirty-two adult male rats were divided into four groups: control, diacerein-treated, NASH-untreated and NASH+diacerein-treated groups. NASH was induced by feeding rats with high-fat and high-cholesterol diet for 12 weeks. Body weight, liver weight, fasting blood glucose and insulin levels for estimation of insulin resistance, blood lipids, alanine transaminase, and aspartate aminotransferase were evaluated. Serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), adiponectin, visfatin and leptin were also detected. Histopathological examination of liver sections was performed.Results: Diacerein significantly reduced liver weight, fasting blood glucose, insulin level, transaminases and ameliorates insulin resistance with favourable effects on blood lipids. These results were accompanied with a significant reduction in serum levels of TNF-α, IL-1β, IL-6, and visfatin, while, adiponectin was significantly increased and leptin was insignificantly affected. Liver sections revealed that diacerein reduced steatosis and lobular inflammatory grades.Conclusions: These data suggest that diacerein administration may have a potential usefulness in the prevention of NASH as a possible result of inhibition of pro-inflammatory cytokines and the beneficial effects on adipokines especially adiponectin and visfatin.

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“…As we known, fever is a type of nonspecific and phylogenetic response to various infectious or non-infectious stimuli. Yeast-induced fever (also called pathogenic fever), which is usually accompanied by certain radical and inflammatory reaction caused by capsular polysaccharides and/or proteins of yeast, is a classical model for pharmacological study of antipyretic medicines [25]. GC/MS combined NMR has been adopted to analyze the metabolic profiling in the plasma in fever rat induced by baker’s yeast and the antipyretic effect of aspirin was also evaluated by metabolomic methods, while those results indicated that the perturbation of amino acid metabolism coupled with energy metabolism, lipid metabolism, and glycometabolism were involved in the yeast induced fever model [26].…”

Section: Discussionmentioning

confidence: 99%

Plasma Metabolomic Profiling to Reveal Antipyretic Mechanism of Shuang-Huang-Lian Injection on Yeast-Induced Pyrexia Rats

Gao

Guo

et al. 2014

PLoS ONE

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Shuang-huang-lian injection (SHLI) is a famous Chinese patent medicine, which has been wildly used in clinic for the treatment of acute respiratory tract infection, pneumonia, influenza, etc. The existing randomized controlled trial (RCT) studies suggested that SHLI could afford a certain anti-febrile action. However, seldom does research concern the pharmacological mechanisms of SHLI. In the current study, we explored plasma metabolomic profiling technique and selected potential metabolic markers to reveal the antipyretic mechanism of SHLI on yeast-induced pyrexia rat model using UPLC-Q-TOF/MS coupled with multivariate statistical analysis and pattern recognition techniques. We discovered a significant perturbance of metabolic profile in the plasma of fever rats and obvious reversion in SHLI-administered rats. Eight potential biomarkers, i.e. 1) 3-hydeoxybutyric acid, 2) leucine, 3) 16∶0 LPC, 4) allocholic acid, 5) vitamin B2, 6) Cys-Lys-His, 7) 18∶2 LPC, and 8) 3-hydroxychola-7, 22-dien-24-oic acid, were screened out by OPLS-DA approach. Five potential perturbed metabolic pathways, i.e. 1) valine, leucine, and isoleucine biosynthesis, 2) glycerophospholipid metabolism, 3) ketone bodies synthesis and degradation, 4) bile acid biosynthesis, and 5) riboflavin metabolism, were revealed to relate to the antipyretic mechanisms of SHLI. Overall, we investigated antipyretic mechanisms of SHLI at metabolomic level for the first time, and the obtained results highlights the necessity of adopting metabolomics as a reliable tool for understanding the holism and synergism of Chinese patent drug.

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Diacerein decreases TNF-α and IL-1β levels in peritoneal fluid and prevents Baker’s yeast-induced fever in young rats

Abstract: These data suggest that diacerein partially protects against Baker's yeast-induced fever and peritoneal leukocyte migration, and indicate that this effect appears to be due to inhibition of release of cytokines (such as TNF-alpha and IL-1beta).

Cited by 32 publications

References 36 publications

ER Stress, P66shc, and P-Akt/Akt Mediate Adjuvant-Induced Inflammation, Which Is Blunted by Argirein, a Supermolecule and Rhein in Rats

ER Stress, P66shc, and P-Akt/Akt Mediate Adjuvant-Induced Inflammation, Which Is Blunted by Argirein, a Supermolecule and Rhein in Rats

Beneficial effects of diacerein on adipokines and pro-inflammatory cytokines involved in diet-induced nonalcoholic steatohepatitis in rats

Plasma Metabolomic Profiling to Reveal Antipyretic Mechanism of Shuang-Huang-Lian Injection on Yeast-Induced Pyrexia Rats

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