Palmitoylethanolamide and luteolin ameliorate development of arthritis caused by injection of collagen type II in mice

Daniela Impellizzeri, Emanuela Esposito, Rosanna Di Paola, Akbar Ahmad, Michela Campolo, Angelo Peli, Valeria M. Morittu, Domenico Britti, Salvatore Cuzzocrea

Research output: Contribution to journalArticle

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Abstract

Introduction: N-palmitoylethanolamine (PEA) is an endogenous fatty acid amide belonging to the family of the N-acylethanolamines (NAEs). Recently, several studies demonstrated that PEA is an important analgesic, antiinflammatory, and neuroprotective mediator. The aim of this study was to investigate the effect of co-ultramicronized PEA + luteolin formulation on the modulation of the inflammatory response in mice subjected to collagen-induced arthritis (CIA).Methods: CIA was induced by an intradermally injection of 100 μl of the emulsion (containing 100 μg of bovine type II collagen (CII)) and complete Freund adjuvant (CFA) at the base of the tail. On day 21, a second injection of CII in CFA was administered. Mice subjected to CIA were administered PEA (10 mg/kg 10% ethanol, intraperitoneally (i.p.)) or co-ultramicronized PEA + luteolin (1 mg/kg, i.p.) every 24 hours, starting from day 25 to 35.Results: Mice developed erosive hind-paw arthritis when immunized with CII in CFA. Macroscopic clinical evidence of CIA first appeared as periarticular erythema and edema in the hindpaws. The incidence of CIA was 100% by day 28 in the CII-challenged mice, and the severity of CIA progressed over a 35-day period with a resorption of bone. The histopathology of CIA included erosion of the cartilage at the joint. Treatment with PEA or PEA + luteolin ameliorated the clinical signs at days 26 to 35 and improved histologic status in the joint and paw. The degree of oxidative and nitrosative damage was significantly reduced in PEA + luteolin-treated mice, as indicated by nitrotyrosine and malondialdehyde (MDA) levels. Plasma levels of the proinflammatory cytokines and chemokines were significantly reduced by PEA + luteolin treatment.Conclusions: We demonstrated that PEA co-ultramicronized with luteolin exerts an antiinflammatory effect during chronic inflammation and ameliorates CIA.

Original languageEnglish (US)
Article numberR192
JournalArthritis Research and Therapy
Volume15
Issue number6
DOIs
StatePublished - Nov 18 2013
Externally publishedYes

Fingerprint

Luteolin
Experimental Arthritis
Collagen Type II
Arthritis
Injections
Freund's Adjuvant
Anti-Inflammatory Agents
Joints
palmidrol
Erythema
Bone Resorption
Emulsions
Malondialdehyde
Chemokines
Amides
Cartilage
Analgesics
Tail
Edema
Ethanol

ASJC Scopus subject areas

  • Rheumatology
  • Immunology
  • Immunology and Allergy
  • Medicine(all)

Cite this

Impellizzeri, D., Esposito, E., Di Paola, R., Ahmad, A., Campolo, M., Peli, A., ... Cuzzocrea, S. (2013). Palmitoylethanolamide and luteolin ameliorate development of arthritis caused by injection of collagen type II in mice. Arthritis Research and Therapy, 15(6), [R192]. https://doi.org/10.1186/ar4382

Palmitoylethanolamide and luteolin ameliorate development of arthritis caused by injection of collagen type II in mice. / Impellizzeri, Daniela; Esposito, Emanuela; Di Paola, Rosanna; Ahmad, Akbar; Campolo, Michela; Peli, Angelo; Morittu, Valeria M.; Britti, Domenico; Cuzzocrea, Salvatore.

In: Arthritis Research and Therapy, Vol. 15, No. 6, R192, 18.11.2013.

Research output: Contribution to journalArticle

Impellizzeri, D, Esposito, E, Di Paola, R, Ahmad, A, Campolo, M, Peli, A, Morittu, VM, Britti, D & Cuzzocrea, S 2013, 'Palmitoylethanolamide and luteolin ameliorate development of arthritis caused by injection of collagen type II in mice', Arthritis Research and Therapy, vol. 15, no. 6, R192. https://doi.org/10.1186/ar4382
Impellizzeri, Daniela ; Esposito, Emanuela ; Di Paola, Rosanna ; Ahmad, Akbar ; Campolo, Michela ; Peli, Angelo ; Morittu, Valeria M. ; Britti, Domenico ; Cuzzocrea, Salvatore. / Palmitoylethanolamide and luteolin ameliorate development of arthritis caused by injection of collagen type II in mice. In: Arthritis Research and Therapy. 2013 ; Vol. 15, No. 6.
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abstract = "Introduction: N-palmitoylethanolamine (PEA) is an endogenous fatty acid amide belonging to the family of the N-acylethanolamines (NAEs). Recently, several studies demonstrated that PEA is an important analgesic, antiinflammatory, and neuroprotective mediator. The aim of this study was to investigate the effect of co-ultramicronized PEA + luteolin formulation on the modulation of the inflammatory response in mice subjected to collagen-induced arthritis (CIA).Methods: CIA was induced by an intradermally injection of 100 μl of the emulsion (containing 100 μg of bovine type II collagen (CII)) and complete Freund adjuvant (CFA) at the base of the tail. On day 21, a second injection of CII in CFA was administered. Mice subjected to CIA were administered PEA (10 mg/kg 10{\%} ethanol, intraperitoneally (i.p.)) or co-ultramicronized PEA + luteolin (1 mg/kg, i.p.) every 24 hours, starting from day 25 to 35.Results: Mice developed erosive hind-paw arthritis when immunized with CII in CFA. Macroscopic clinical evidence of CIA first appeared as periarticular erythema and edema in the hindpaws. The incidence of CIA was 100{\%} by day 28 in the CII-challenged mice, and the severity of CIA progressed over a 35-day period with a resorption of bone. The histopathology of CIA included erosion of the cartilage at the joint. Treatment with PEA or PEA + luteolin ameliorated the clinical signs at days 26 to 35 and improved histologic status in the joint and paw. The degree of oxidative and nitrosative damage was significantly reduced in PEA + luteolin-treated mice, as indicated by nitrotyrosine and malondialdehyde (MDA) levels. Plasma levels of the proinflammatory cytokines and chemokines were significantly reduced by PEA + luteolin treatment.Conclusions: We demonstrated that PEA co-ultramicronized with luteolin exerts an antiinflammatory effect during chronic inflammation and ameliorates CIA.",
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T1 - Palmitoylethanolamide and luteolin ameliorate development of arthritis caused by injection of collagen type II in mice

AU - Impellizzeri, Daniela

AU - Esposito, Emanuela

AU - Di Paola, Rosanna

AU - Ahmad, Akbar

AU - Campolo, Michela

AU - Peli, Angelo

AU - Morittu, Valeria M.

AU - Britti, Domenico

AU - Cuzzocrea, Salvatore

PY - 2013/11/18

Y1 - 2013/11/18

N2 - Introduction: N-palmitoylethanolamine (PEA) is an endogenous fatty acid amide belonging to the family of the N-acylethanolamines (NAEs). Recently, several studies demonstrated that PEA is an important analgesic, antiinflammatory, and neuroprotective mediator. The aim of this study was to investigate the effect of co-ultramicronized PEA + luteolin formulation on the modulation of the inflammatory response in mice subjected to collagen-induced arthritis (CIA).Methods: CIA was induced by an intradermally injection of 100 μl of the emulsion (containing 100 μg of bovine type II collagen (CII)) and complete Freund adjuvant (CFA) at the base of the tail. On day 21, a second injection of CII in CFA was administered. Mice subjected to CIA were administered PEA (10 mg/kg 10% ethanol, intraperitoneally (i.p.)) or co-ultramicronized PEA + luteolin (1 mg/kg, i.p.) every 24 hours, starting from day 25 to 35.Results: Mice developed erosive hind-paw arthritis when immunized with CII in CFA. Macroscopic clinical evidence of CIA first appeared as periarticular erythema and edema in the hindpaws. The incidence of CIA was 100% by day 28 in the CII-challenged mice, and the severity of CIA progressed over a 35-day period with a resorption of bone. The histopathology of CIA included erosion of the cartilage at the joint. Treatment with PEA or PEA + luteolin ameliorated the clinical signs at days 26 to 35 and improved histologic status in the joint and paw. The degree of oxidative and nitrosative damage was significantly reduced in PEA + luteolin-treated mice, as indicated by nitrotyrosine and malondialdehyde (MDA) levels. Plasma levels of the proinflammatory cytokines and chemokines were significantly reduced by PEA + luteolin treatment.Conclusions: We demonstrated that PEA co-ultramicronized with luteolin exerts an antiinflammatory effect during chronic inflammation and ameliorates CIA.

AB - Introduction: N-palmitoylethanolamine (PEA) is an endogenous fatty acid amide belonging to the family of the N-acylethanolamines (NAEs). Recently, several studies demonstrated that PEA is an important analgesic, antiinflammatory, and neuroprotective mediator. The aim of this study was to investigate the effect of co-ultramicronized PEA + luteolin formulation on the modulation of the inflammatory response in mice subjected to collagen-induced arthritis (CIA).Methods: CIA was induced by an intradermally injection of 100 μl of the emulsion (containing 100 μg of bovine type II collagen (CII)) and complete Freund adjuvant (CFA) at the base of the tail. On day 21, a second injection of CII in CFA was administered. Mice subjected to CIA were administered PEA (10 mg/kg 10% ethanol, intraperitoneally (i.p.)) or co-ultramicronized PEA + luteolin (1 mg/kg, i.p.) every 24 hours, starting from day 25 to 35.Results: Mice developed erosive hind-paw arthritis when immunized with CII in CFA. Macroscopic clinical evidence of CIA first appeared as periarticular erythema and edema in the hindpaws. The incidence of CIA was 100% by day 28 in the CII-challenged mice, and the severity of CIA progressed over a 35-day period with a resorption of bone. The histopathology of CIA included erosion of the cartilage at the joint. Treatment with PEA or PEA + luteolin ameliorated the clinical signs at days 26 to 35 and improved histologic status in the joint and paw. The degree of oxidative and nitrosative damage was significantly reduced in PEA + luteolin-treated mice, as indicated by nitrotyrosine and malondialdehyde (MDA) levels. Plasma levels of the proinflammatory cytokines and chemokines were significantly reduced by PEA + luteolin treatment.Conclusions: We demonstrated that PEA co-ultramicronized with luteolin exerts an antiinflammatory effect during chronic inflammation and ameliorates CIA.

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