Polyphenol containing Sargassum horneri attenuated Th2 differentiation in splenocytes of ovalbumin-sensitised mice: involvement of the transcription factors GATA3/STAT5/NLRP3 in Th2 polarization

Pharm Biol. 2021 Dec;59(1):1464-1472. doi: 10.1080/13880209.2021.1992451.

Abstract

Context: Sargassum horneri (Turner) C. Agardh (Sargassaceae) is a brown marine alga used in oriental medicine to treat allergic conditions.

Objective: This study clarifies the effect of polyphenol-containing S. horneri ethanol extract (SHE) on T-helper type-2 (Th2) polarisation.

Materials and methods: All mice (BALB/c mice, n = 12) except in the healthy control group were first sensitised with an intraperitoneal injection of ovalbumin (OVA; 20 µg) and alum (2 mg) on Day 0 and Day 14. Similarly, phosphate-buffered saline (PBS) was injected according to the same schedule into the healthy control mice. After the final administration, splenocytes were obtained. OVA sensitised mice were challenged with OVA (100 µg/mL) in the absence or presence (62.5 and 125 µg/mL) of SHE while healthy control group remained untreated.

Results: SHE (0-1000 µg/mL) was not cytotoxic to splenocytes and demonstrated IC50 values of 3.27 and 3.92 mg/mL, respectively, at 24 and 48 h of incubation. SHE suppressed cell proliferation at concentrations ≥62.5 µg/mL. SHE treatment (125 µg/mL) subdued (by 1.8-fold) the population expansion of CD3+CD4+ helper T cells induced by OVA challenge. SHE attenuated the OVA-induced activation of respective transcription factors GATA3 and NLRP3. Simultaneously, highly elevated levels of cytokines interleukin (IL)-4 and IL-5 caused by OVA stimulation were removed completely and IL-13 suppressed by 1.5-fold.

Conclusions: SHE exhibits Th2 immune suppression under OVA stimulation via GATA3- and NLRP3-dependent IL-4, IL-5, and IL-13 suppression. Therefore, SHE could be therapeutically useful for alleviating the symptoms of allergen-mediated immune diseases.

Keywords: CD3+ CD4+ T cell; IL-13; Polyphenol.

MeSH terms

  • Animals
  • Cytokines / immunology
  • Dose-Response Relationship, Drug
  • GATA3 Transcription Factor / metabolism
  • Mice
  • Mice, Inbred BALB C
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Ovalbumin
  • Plant Extracts / administration & dosage
  • Plant Extracts / pharmacology*
  • Polyphenols / administration & dosage
  • Polyphenols / isolation & purification
  • Polyphenols / pharmacology*
  • STAT5 Transcription Factor / metabolism
  • Sargassum / chemistry*
  • Spleen / cytology
  • Spleen / drug effects
  • Spleen / immunology
  • Th2 Cells / immunology*

Substances

  • Cytokines
  • GATA3 Transcription Factor
  • Gata3 protein, mouse
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse
  • Plant Extracts
  • Polyphenols
  • STAT5 Transcription Factor
  • Stat5a protein, mouse
  • Ovalbumin

Grants and funding

This research is a part of the project “Development of functional food products with natural materials derived from marine resources,” funded by the Ministry of Oceans and Fisheries, Korea [Project No. 20150306 and 20170285]. We wish to thank Dr T.H. Chung for the editorial assistance.