Isoflavones Suppress Cyp26b1 Expression in the Murine Colonic Lamina Propria

Biol Pharm Bull. 2020;43(12):1945-1949. doi: 10.1248/bpb.b20-00355.

Abstract

Isoflavones have many biological activities and are major bioactive components of kakkonto, a traditional Japanese herbal medicine. We previously reported that the combined therapy of oral immune therapy (OIT) and kakkonto downregulates the mRNA expression of Cyp26b1, a major retinoic acid (RA)-degrading enzyme, in the colon of food allergy mice and thereby ameliorates allergic symptoms. In this study, we evaluated the effects of various isoflavones on Cyp26b1 expression in primary cultured lamina propria (LP) cells isolated from the mouse colon. The mRNA expression of Cyp26b1 was extremely downregulated by all isoflavones tested in the LP cells except for puerarin. In particular, genistein and genistin markedly suppressed Cyp26b1 mRNA expression without affecting RA-synthesizing enzyme expression. Moreover, to evaluate the effects of isoflavones on allergic reactions, genistein and genistin were administered to ovalbumin (OVA)-induced food allergy mice. Oral administration of genistin suppressed the development of allergic symptoms. These results raise the possibility that isoflavones elevated the level of RA in the colon by inhibiting RA degradation and then the high concentration of RA in the colon might exert immunosuppressive and antiallergic effects on food allergy mice.

Keywords: Cyp26b1; colonic lamina propria; food allergy; genistein; genistin.

MeSH terms

  • Animals
  • Colon / drug effects*
  • Colon / enzymology*
  • Food Hypersensitivity / drug therapy
  • Food Hypersensitivity / enzymology
  • Food Hypersensitivity / etiology
  • Gene Expression Regulation, Enzymologic
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / enzymology*
  • Isoflavones / pharmacology*
  • Isoflavones / therapeutic use
  • Mice
  • Mice, Inbred BALB C
  • Mucous Membrane / drug effects
  • Mucous Membrane / enzymology
  • Ovalbumin / toxicity
  • Retinoic Acid 4-Hydroxylase / antagonists & inhibitors
  • Retinoic Acid 4-Hydroxylase / biosynthesis*

Substances

  • Isoflavones
  • genistin
  • Ovalbumin
  • Retinoic Acid 4-Hydroxylase