Synergistic anti-inflammatory activity of apigenin and curcumin co-encapsulated in caseins assessed with lipopolysaccharide-stimulated RAW 264.7 macrophages

Int J Biol Macromol. 2021 Dec 15;193(Pt A):702-712. doi: 10.1016/j.ijbiomac.2021.10.153. Epub 2021 Oct 27.

Abstract

Dietary polyphenols are potential anti-inflammatory agents, and their combinations with enhanced biological activities may lower toxicity and side effects. The objective of this work was to investigate the potential synergistic anti-inflammatory activities of apigenin and curcumin co-nanoencapsulated in sodium caseinate, with comparison to unencapsulated polyphenol combinations. Non-toxic concentrations of apigenin, curcumin, and their combinations in the free and co-encapsulated forms were studied in lipopolysaccharide-stimulated RAW 264.7 macrophage cells. Combinations of free polyphenols produced stronger inhibition of nitric oxide (NO) production, more significant at a higher proportion of curcumin, which was further enhanced after co-encapsulation. The enhanced reduction of NO was concomitant with the decreased expression of iNOS, the enhanced inhibition of pro-inflammatory cytokines of IL-6 and TNF-α, and the reduced production of intracellular reactive oxygen species. The potential multi-target effects and the enhanced solubility, proximity, and bioavailability of AP and CUR after co-encapsulation contributed to the synergistic activities. These results demonstrated that co-nanoencapsulation of apigenin and curcumin may enable the practical application utilizing the synergistic anti-inflammation effects to improve health.

Keywords: Apigenin; Co-encapsulation; Curcumin; Sodium caseinate; Synergistic anti-inflammatory activity.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology*
  • Apigenin / chemistry
  • Apigenin / pharmacology*
  • Biological Availability
  • Caseins
  • Cell Survival / drug effects
  • Curcumin / chemistry
  • Curcumin / pharmacology*
  • Cytokines / metabolism
  • Inflammation / drug therapy
  • Interleukin-6
  • Lipopolysaccharides / adverse effects*
  • Macrophages / drug effects*
  • Mice
  • Nitric Oxide / metabolism
  • Particle Size
  • Polyphenols / pharmacology
  • RAW 264.7 Cells
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • Caseins
  • Cytokines
  • Interleukin-6
  • Lipopolysaccharides
  • Polyphenols
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • Apigenin
  • Curcumin