Nutr Res Pract.  2022 Oct;16(5):577-588. 10.4162/nrp.2022.16.5.577.

Pear pomace alleviated atopic dermatitis in NC/Nga mice and inhibited LPS-induced inflammation in RAW 264.7 macrophages

• You M
• Wang Z
• Kim HJ
• Lee YH
• Kim HA

• KMID: 2534117
• DOI: http://doi.org/10.4162/nrp.2022.16.5.577

Abstract

BACKGROUND/OBJECTIVES
Poorly regulated inflammation is believed to be the most predominant factor that can result in a wide scope of diseases including atopic dermatitis (AD). Despite many studies on the effect of pear pomace in obesity-related disorders including dysregulated gut microbiota, the protective effect of pear pomace in AD is still unknown. This study aimed to evaluate the effect of pear pomace ethanol extract (PPE) on AD by inhibiting inflammation.
MATERIALS/METHODS
In the in vivo experiment, 2, 4-dinitrochlorobenzene (DNCB) was applied to NC/Nga mice to induce AD-like skin lesions. After the induction, PPE was administered daily by oral gavage for 4 weeks. The clinical severity score, serum IgE levels, spleen weight, histological changes in dorsal skin, and inflammation-related proteins were measured. In the cell study, RAW 264.7 cells were pretreated with PPE before stimulation with lipopolysaccharide (LPS). Nitrite oxide (NO) production and nuclear factor kappa B (NFkB) protein expression were detected.
RESULTS
Compared to the AD control (AD-C) group, IgE levels were dramatically decreased via PPE treatment. PPE significantly reduced scratching behavior, improved skin symptoms, and decreased ear thickness compared to the AD-C group. In addition, PPE inhibited the DNCB-induced expression of inducible nitrite oxide synthase (iNOS), the receptor for advanced glycation end products, extracellular signal-regulated kinase (ERK) 1/2, and NF-κB. PPE inhibited the LPS-induced overproduction of NO and the enhanced expression of iNOS and cyclooxygenase-2. Moreover, the phosphorylation of ERK1/2 and NF-κB in RAW 264.7 cells was suppressed by PPE.
CONCLUSIONS
These results suggest that PPE could be explored as a therapeutic agent to prevent AD.

Keyword

Pyrus; atopic dermatitis; inflammation

Figure

• 

  Fig. 1 Pear pomace ameliorated AD symptoms in DNCB-induced AD skin lesion in NC/Nga mice. (A) Experiment design. To induce AD-like lesions, DNCB was applied to NC/Nga mice (n = 7). The mice were sensitized with 1% DNCB for 1 week and then challenged with 0.4% DNCB solution for 7 weeks. The mice were administered PBS or PPE daily for 4 weeks. (B) Final body weight. (C) Serum levels of IgE. (D) Total scratching behavior scores 7 weeks after sensitization. (E) Clinical severity score for dermatitis on the necropsy day. (F) Spleen weight. (G) Skin thickness. (H) Ear thickness.AD, atopic dermatitis; DNCB, 2, 4-dinitrochlorobenzene; PBS, phosphate-buffed saline; PPE, pear pomace ethanol extract; Cont, no sensitization; AD-C, DNCB treatment with oral administration of PBS (AD control); AD + PPE 200, DNCB treatment with oral administration of PPE 200 mg/kg body weight; AD + PPE 400, DNCB treatment with oral administration of PPE 400 mg/kg body weight.Different letters are significantly different by Duncan’s multiple range test (P < 0.05).

• 

  Fig. 2 Histological changes in the dorsal skin in pear pomace-treated NC/Nga mice. (A) H&E staining in skin tissue. (B) Toluidine blue staining. The arrows indicate mast cells in the skin tissue.AD, atopic dermatitis; DNCB, 2, 4-dinitrochlorobenzene; H&E, hematoxylin and eosin; PPE, pear pomace ethanol extract; Cont, no sensitization; AD-C, DNCB treatment with the oral administration of PBS (AD control); AD + PPE 200, DNCB treatment with the oral administration of PPE 200 mg/kg body weight; AD + PPE 400, DNCB treatment with oral administration of PPE 400 mg/kg body weight.

• 

  Fig. 3 Applications of pear pomace inhibited inflammation-related proteins in the skin tissue of NC/Nga mice. β-actin was used as the control for quantification.Cont, no sensitization; AD-C, DNCB treatment with oral administration of PBS (AD control); AD + PPE 200, DNCB treatment with the oral administration of PPE 200 mg/kg body weight; AD + PPE 400, DNCB treatment with the oral administration of PPE 400 mg/kg body weight; RAGE, receptor for advanced glycation end products; ERK, extracellular signal-regulated kinase, NF-κB, nuclear factor kappa B; iNOS, inducible nitrite oxide synthase; PPE, pear pomace ethanol extract.Different letters are significantly different by Duncan’s multiple range test (P < 0.05).

• 

  Fig. 4 Inhibitory effects of pear pomace on the inflammatory response in LPS-induced inflammation in RAW 264.7 macrophages. RAW 264.7 cells were pretreated with either 0, 100, or 250 ug/mL of PPE for 1 h before the addition of 1 ug/mL of LPS treatment for 24 h. (A) Cell viability. (B) NO production. (C) Protein expression of iNOS and COX-2. (D) Protein expression of ERK and NF-κB. β-actin was used as the control for quantification.LPS, lipopolysaccharide; NO, nitrite oxide; iNOS, inducible nitrite oxide synthase; COX-2, cyclooxygenase-2; ERK, extracellular signal-regulated kinase; NF-κB, nuclear factor kappa B; PPE, pear pomace ethanol extract.Different letters are significantly different by Duncan’s multiple range test (P < 0.05).

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